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Number of genes required to sustain life

Number of genes required to sustain life



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Are there estimates of the minimum number of genes required to sustain life?

In what I mean by life here, I don't include viruses.


Depends on what kind of life you want! The Database of Essential Genes lists genes essential for life for a number of species, although I would be wary of some of the numbers; bacterial results are probably more reliable but it lists 118 for humans and 2114 for mice. There are a bunch of different numbers for different E. coli strains, with larger numbers being published earlier, go figure.

It of course varies by species. In mid-August of this year, scientists reported the smallest genome yet: 112kb with only 137 protein-coding genes (predicted). Crazy! That doesn't mean it's the smallest number of genes though, just what we've found. Some folks in 2006 predicted the smallest would be 113kb and 151 genes - pretty close close to the above, all in all.

For something a little more familiar and studied, though, Craig Venter has made synthetic biology his goal. Part of trying to create life is knowing what the bare minimum is. Working with Mycoplasma genitalium, he and his crew knocked out each gene and found that 381 were indeed essential.


Minimal genome

The minimal genome concept assumes that genomes can be reduced to a bare minimum, given that they contain many non-essential genes of limited or situational importance to the organism. Therefore, if a collection of all the essential genes were put together, a minimum genome could be created artificially in a stable environment. By adding more genes, the creation of an organism of desired properties is possible. The concept of minimal genome arose from the observations that many genes do not appear to be necessary for survival. [1] [2] In order to create a new organism a scientist must determine the minimal set of genes required for metabolism and replication. This can be achieved by experimental and computational analysis of the biochemical pathways needed to carry out basic metabolism and reproduction. [3] A good model for a minimal genome is Mycoplasma genitalium due to its very small genome size. Most genes that are used by this organism are usually considered essential for survival based on this concept a minimal set of 256 genes has been proposed. [4]


Chapter 21 - The Genetic Basis of Development

  • During differentiation and morphogenesis, embryonic cells behave and function in ways different from one another, even though all of them have arisen from the same zygote.
  • The differences between cells in a multicellular organism come almost entirely from differences in gene expression, not differences in the cell’s genomes.
  • These differences arise during development, as regulatory mechanisms turn specific genes off and on.

Different types of cells in an organism have the same DNA.

  • Much evidence supports the conclusion that nearly all the cells of an organism have genomic equivalence—that is, they all have the same genes.
  • An important question that emerges is whether genes are irreversibly inactivated during differentiation.
  • One experimental approach to the question of genomic equivalence is to try to generate a whole organism from differentiated cells of a single type.
    • In many plants, whole new organisms can develop from differentiated somatic cells.
    • During the 1950s, F. C. Steward and his students found that differentiated root cells removed from the root could grow into normal adult plants when placed in a medium culture.
    • They retain the zygote’s potential to form all parts of the mature organism.
    • The pioneering experiments in nuclear transplantation were carried out by Robert Briggs and Thomas King in the 1950s and extended later by John Gordon in the 1980s.
    • They destroyed or removed the nucleus of a frog egg and transplanted a nucleus from an embryonic or tadpole cell from the same species into an enucleated egg.
    • Transplanted nuclei from relatively undifferentiated cells from an early embryo lead to the development of most eggs into tadpoles.
    • Transplanted nuclei from fully differentiated intestinal cells lead to fewer than 2% of the cells developing into normal tadpoles.
      • Most of the embryos failed to make it through even the earliest stages of development.
      • First, nuclei do change in some ways as cells differentiate.
        • While the DNA sequences do not change, histones may be modified or DNA may be methylated.
        • However, chromatin changes are sometimes reversible, and the nuclei of most differentiated animal cells probably have all the genes required for making an entire organism.
        • The resulting cells divided to form early embryos, which were implanted into surrogate mothers.
        • Dolly’s premature death as well as her arthritis led to speculation that her cells were older than those of a normal sheep, possibly reflecting incomplete reprogramming of the original transplanted nucleus.
        • In most cases, the goal is to produce new individuals.
        • This is known as reproductive cloning.
        • Cloned animals in the same species do not look or behave identically.
        • Clearly, environmental influences and random phenomena can play a significant role during development.
        • In early 2004, South Korean researchers reported success in the first step of reproductive cloning of humans.
        • Nuclei from differentiated human cells were transplanted into unfertilized enucleated eggs.
          • The eggs divided, and some embryos reached the blastocyst stage before development was halted.
          • Like Dolly, many cloned animals have various defects, such as obesity, pneumonia, liver failure, and premature death.
          • This regulation is often the result of epigenetic changes in chromatin, such as the acetylation of histones or the methylation of DNA.
          • Many of these changes must be reversed in the nucleus of the donor animal in order for genes to be expressed or repressed appropriately for early stages of development.
          • Researchers have found that the DNA in embryonic cells from cloned embryos, like that of differentiated cells, often has more methyl groups than does the DNA in equivalent cells from uncloned embryos of the same species.
          • Because DNA methylation helps regulate gene expression, methylated DNA of donor nuclei may interfere with the pattern of gene expression necessary for normal embryonic development.
          • A stem cell is a relatively unspecialized cell that can reproduce itself and, under appropriate conditions, differentiate into specialized cell types.
          • The ultimate goal is to supply cells for the repair of damaged or diseased organs.
          • For example, providing insulin-producing pancreatic cells to diabetics or certain brain cells to individuals with Parkinson’s disease could cure these diseases.
          • In culture, these embryonic stem cells reproduce indefinitely and can differentiate into various specialized cells.
          • Adult stem cells are said to be pluripotent, able to give rise to many, but not all, cell types.
            • For example, stem cells in the bone marrow give rise to all the different kinds of blood cells.
            • Under some culture conditions, with the addition of specific growth factors, cultured adult stem cells can differentiate into multiple types of specialized cells.
            • Embryonic stem cells are currently obtained from embryos donated by parents undergoing fertility treatments, or from long-term cell cultures originally established with cells isolated from donated embryos.
            • Because the cells are derived from human embryos, their use raises ethical and political issues.
            • With the recent cloning of human embryos to the blastocyst stage, scientists might be able to use these clones as the source of embryonic stem cells in the future.
            • When the major aim of cloning is to produce embryonic stem cells to treat disease, the process is called therapeutic cloning.
              • Opinions vary about the morality of therapeutic cloning.

              Different cell types make different proteins, usually as a result of transcriptional regulation.

              • During embryonic development, cells become visibly different in structure and function as they differentiate.
              • The earliest changes that set a cell on a path to specialization show up only at the molecular level.
              • Molecular changes in the embryo drive the process, termed determination, which leads up to observable differentiation of a cell.
                • At the end of this process, an embryonic cell is irreversibly committed to its final fate.
                • If a determined cell is experimentally placed in another location in the embryo, it will differentiate as if it were in its original position.
                • These give a cell its characteristic structure and function.
                • Differentiation begins with the appearance of mRNA and is finally observable in the microscope as changes in cellular structure.
                • For example, lens cells, and only lens cells, devote 80% of their capacity for protein synthesis to making just one type of protein, crystallin proteins.
                  • These form transparent fibers that allow the lens to transmit and focus light.
                  • They also have membrane receptor proteins that detect signals from nerve cells.
                  • As the muscle cells differentiate, they become myoblasts and begin to synthesize muscle-specific proteins.
                  • They fuse to form mature, elongated, multinucleate skeletal muscle cells.
                  • To test this, researchers isolated mRNA from cultured myoblasts and used reverse transcriptase to prepare a cDNA library containing all the genes that are expressed in cultured myoblasts.
                  • Transplanting these cloned genes into embryonic precursor cells led to the identification of several “master regulatory genes” that, when transcribed and translated, commit the cells to become skeletal muscle.
                  • myoD encodes MyoD protein, which binds to specific control elements and stimulates the transcription of various genes, including some that encode for other muscle-specific transcription factors.
                    • These secondary transcription factors activate the muscle protein genes.
                    • MyoD also stimulates expression of the myoD gene itself, perpetuating its effect in maintaining the cell’s differentiated state.
                    • Nontransforming cells may lack a combination of regulatory proteins, in addition to MyoD.

                    Transcriptional regulation is directed by maternal molecules in the cytoplasm and signals from other cells.

                    • Two sources of information “tell” a cell, such as a myoblast or even the zygote, which genes to express at any given time.
                    • One source of information is the cytoplasm of the unfertilized egg cell, which contains RNA and protein molecules encoded by the mother’s DNA.
                      • Messenger RNA, proteins, other substances, and organelles are distributed unevenly in the unfertilized egg.
                      • This impacts embryonic development in many species.
                      • These substances regulate the expression of genes that affect the developmental fate of the cell.
                      • After fertilization, the cell nuclei resulting from mitotic division of the zygote are exposed to different cytoplasmic environments.
                        • The set of cytoplasmic determinants a particular cell receives helps determine its developmental fate by regulating expression of the cell’s genes during the course of cell differentiation.
                        • In animals, these include contact with cell-surface molecules on neighboring cells and the binding of growth factors secreted by neighboring cells.
                        • In plants, the cell-cell junctions known as plasmodesmata allow signal molecules to pass from one cell to another.
                          • The synthesis of these signals is controlled by the embryo’s own genes.

                          Concept 21.3 Pattern formation in animals and plants results from similar genetic and cellular mechanisms

                          • Before morphogenesis can shape an animal or plant, the organism’s body plan must be established.
                          • Cytoplasmic determinants and inductive signals contribute to pattern formation, the development of spatial organization in which the tissues and organs of an organism are all in their characteristic places.
                            • Pattern formation continues throughout the life of a plant in the apical meristems.
                            • In animals, pattern formation is mostly limited to embryos and juveniles.
                            • The molecular cues that control pattern formation, positional information, tell a cell its location relative to the body axes and to neighboring cells.
                            • They also determine how the cells and their progeny will respond to future molecular signals.

                            Drosophila development is controlled by a cascade of gene activations.

                            • Pattern formation has been most extensively studied in Drosophila melanogaster, where genetic approaches have had spectacular success.
                              • These studies have established that genes control development and have identified the key roles that specific molecules play in defining position and directing differentiation.
                              • Combining anatomical, genetic, and biochemical approaches in the study of Drosophila development, researchers have discovered developmental principles common to many other species, including humans.
                              • These segments make up the three major body parts: the head, thorax (with wings and legs), and abdomen.
                              • Like other bilaterally symmetrical animals, Drosophila has an anterior-posterior axis and a dorsal-ventral axis.
                                • Cytoplasmic determinants in the unfertilized egg provide positional information for the two developmental axes before fertilization.
                                1. Mitosis follows fertilization and egg laying.
                                  • Early mitosis occurs without growth of the cytoplasm and without cytokinesis, producing one big multinucleate cell.
                                2. At the tenth nuclear division, the nuclei begin to migrate to the periphery of the embryo.
                                3. At division 13, the cytoplasm partitions the 6,000 or so nuclei into separate cells.
                                  • The basic body plan—including body axes and segment boundaries—has already been determined by this time.
                                  • A central yolk nourishes the embryo, and the eggshell continues to protect it.
                                4. Subsequent events in the embryo create clearly visible segments, which at first look very much alike.
                                5. Some cells move to new positions, organs form, and a wormlike larva hatches from the shell.
                                  • During three larval stages, the larva eats, grows, and molts.
                                6. During the third larval stage, the larva transforms into the pupa enclosed in a case.
                                7. Metamorphosis, the change from larva to adult fly, occurs in the pupal case, and the fly emerges.
                                  • Each segment is anatomically distinct, with characteristic appendages.
                                • Because Drosophila has about 13,700 genes, there could be only a few genes affecting segmentation or so many that the pattern would be impossible to discern.
                                • Mutations that affect segmentation are likely to be embryonic lethals, leading to death at the embryonic or larval stage.
                                  • Because flies with embryonic lethal mutations never reproduce, they cannot be bred for study.
                                  • After mutating flies, they looked for dead embryos and larvae with abnormal segmentation among the fly’s descendents.
                                  • Through appropriate crosses, they could identify living heterozygotes carrying embryonic lethal mutations.
                                  • They hoped that the segmental abnormalities would suggest how the affected genes normally functioned.
                                  • About 120 of these were essential for pattern formation leading to normal segmentation.
                                  • After several years, they were able to group the genes by general function, map them, and clone many of them.
                                  • In 1995, Nüsslein-Volhard, Wieschaus, and Lewis were awarded the Nobel Prize.

                                  Gradients of maternal molecules in the early embryo control axis formation.

                                  • Cytoplasmic determinants establish the axes of the Drosophila body.
                                    • Substances are produced under the direction of maternal effect genes that are deposited in the unfertilized egg.
                                      • When a maternal effect gene is mutated, the offspring has an abnormal mutant phenotype.
                                      • When the mother has a mutated gene, she makes a defective gene product (or none at all), and her eggs will not develop properly when fertilized.
                                      • One group of genes sets up the anterior-posterior axis, while a second group establishes the dorsal-ventral axis.
                                      • This suggests that the product of the mother’s bicoid gene is essential for setting up the anterior end of the fly.
                                      • It also suggests that the gene’s products are concentrated at the future anterior end.
                                      • As predicted, the bicoid mRNA is concentrated at the extreme anterior end of the egg cell.
                                      1. It identified a specific protein required for some of the earliest steps in pattern formation.
                                      2. It increased our understanding of the mother’s role in development of an embryo.
                                        • As one developmental biologist put it, “Mom tells Junior which way is up.”
                                      3. It demonstrated a key developmental principle that a gradient of molecules can determine polarity and position in the embryo.
                                        • Gradients of specific proteins determine the posterior end as well as the anterior and also are responsible for establishing the dorsal-ventral axis.

                                      A cascade of gene activations sets up the segmentation pattern in Drosophila.

                                      • The bicoid protein and other morphogens are transcription factors that regulate the activity of some of the embryo’s own genes.
                                      • Gradients of these morphogens bring about regional differences in the expression of segmentation genes, the genes that direct the actual formation of segments after the embryo’s major axes are defined.
                                      • In a cascade of gene activations, sequential activation of three sets of segmentation genes provides the positional information for increasingly fine details of the body plan.
                                        • The three sets are called gap genes, pair-rule genes, and segment polarity genes.
                                        • Some are components of cell-signaling pathways, including signal molecules used in cell-cell communication and the membrane receptors that recognize them.

                                        Homeotic genes direct the identity of body parts.

                                        • In a normal fly, structures such as antennae, legs, and wings develop on the appropriate segments.
                                        • The anatomical identity of the segments is controlled by master regulatory genes, the homeotic genes.
                                        • Discovered by Edward Lewis, these genes specify the types of appendages and other structures that each segment will form.
                                        • Mutations to homeotic genes produce flies with such strange traits as legs growing from the head in place of antennae.
                                          • Structures characteristic of a particular part of the animal arise in the wrong place.
                                          • For example, a homeotic protein made in a thoracic segment may activate genes that bring about leg development, while a homeotic protein in a certain head segment activates genes for antennal development.
                                          • A mutant version of this protein may label a segment as “thoracic” instead of “head,” causing legs to develop in place of antennae.

                                          Neighboring cells instruct other cells to form particular structures: cell signaling and induction in the nematode.

                                          • The development of a multicellular organism requires close communication among cells.
                                            • Signals generated by neighboring nurse cells trigger the localization of bicoid mRNA in the egg of the Drosophila.
                                            • Induction brings about cell differentiation through transcriptional regulation of specific genes.
                                            • Already present on the ventral surface of the second-stage larva are six cells from which the vulva will arise.
                                            • A single cell in the embryonic gonad, the anchor cell, initiates a cascade of signals that establishes the fate of the six vulval precursor cells.
                                            • If an experimenter destroys the anchor cell with a laser beam, the vulva fails to form and the precursor cells simply become part of the worm’s epidermis.
                                            • In the developing embryo, sequential inductions drive organ formation.
                                            • The effect of an inducer can depend on its concentration.
                                            • Inducers produce their effects via signal transduction pathways similar to those operating in adult cells.
                                            • The induced cell’s response is often the activation of genes—transcriptional regulation—that, in turn, establishes a pattern of gene activity characteristic of a particular kind of differentiated cell.
                                            • The timely suicide of cells occurs exactly 131 times in the course of C. elegans’s normal development.
                                            • At precisely the same points in development, signals trigger the activation of a cascade of “suicide” proteins in the cells destined to die.
                                            • Neighboring cells quickly engulf and digest the membrane-bound remains, leaving no trace.
                                            • ced-9 acts as a brake in the absence of a signal promoting apoptosis.
                                            • The apoptosis pathway activates proteases and nucleases to cut up the proteins and DNA of the cell.
                                            • In nematodes, Ced-3 is the chief caspase—the main protease of apoptosis.
                                            • Signals from apoptosis pathways or others somehow cause the outer mitochondrial membrane to leak, releasing proteins that promote apoptosis.
                                              • Surprisingly, these proteins include cytochrome c, which functions in mitochondrial electron transport in healthy cells but acts as a cell death factor when released from mitochondria.
                                              • Similarities between the apoptosis genes in mammals and nematodes, as well as the observation that apoptosis occurs in multicellular fungi and unicellular yeast, indicate that the basic mechanism evolved early in animal evolution.
                                              • The timely activation of apoptosis proteins in some cells functions during normal development and growth in both embryos and adults.
                                                • It is part of the normal development of the nervous system, normal operation of the immune system, and normal morphogenesis of human hands and feet.
                                                • Failure of normal cell death during morphogenesis of the hands and feet can result in webbed fingers and toes.
                                                • Researchers are also investigating the possibility that certain degenerative diseases of the nervous system result from inappropriate activation of the apoptosis genes.
                                                • Others are investigating the possibility that some cancers result from a failure of cell suicide that normally occurs if the cell has suffered irreparable damage, especially DNA damage.
                                                  • Damaged cells normally generate internal signals that trigger apoptosis.

                                                  Plant development depends on cell signaling and transcriptional regulation.

                                                  • The genetic analysis of plant development, using model organisms such as Arabidopsis, has lagged behind that of animal models.
                                                    • Biologists are just beginning to understand the molecular basis of plant development.
                                                    • Many plant cells are totipotent, and their fates depend more on positional information than on cell lineage.
                                                    • These give rise to new organs, such as leaves or the petals of flowers.
                                                    • A floral meristem is a “bump” with three cell layers, all of which participate in the formation of a flower with four types of organs: carpels (containing egg cells), petals, stamens (containing sperm-bearing pollen), and sepals (leaflike structures outside the petals).
                                                    • Plants homozygous for the mutant allele fasciated (f) produce flowers with an abnormally large number of organs.
                                                    • This induces the L2 and L1 layers to form that number of organs.
                                                    • Mutations cause plant structures to grow in unusual places, such as carpels in the place of sepals.
                                                    • In plants with a “homeotic” mutation, specific organs are missing or repeated.
                                                    • Like the homeotic genes of animals, the organ identity genes of plants encode transcription factors that regulate specific target genes by binding to their enhancers in the DNA.

                                                    Concept 21.4 Comparative studies help explain how the evolution of development leads to morphological diversity

                                                    • Biologists in the field of evolutionary developmental biology, or “evo-devo,” compare developmental processes of different multicellular organisms.
                                                      • Their aim is to understand how developmental processes have evolved and how changes in the processes can modify existing organismal features or lead to new ones.
                                                      • Biologists are finding that the genomes of related species with strikingly different forms may have only minor differences in gene sequence or regulation.
                                                      • An identical, or very similar, sequence of nucleotides (often called Hox genes) is found in many other animals, including humans.
                                                      • The vertebrate genes homologous to the homeotic genes of fruit flies have even kept their chromosomal arrangement.
                                                      • Related sequences have been found in the regulatory genes of plants, yeasts, and even prokaryotes.
                                                      • For example, in Drosophila, homeoboxes are present not only in the homeotic genes, but also in the egg-polarity gene bicoid, in several segmentation genes, and in the master regulatory gene for eye development.
                                                      • However, the shape of the homeodomain allows it to bind to any DNA segment.
                                                      • Other, more variable, domains of the overall protein determine which genes it will regulate.
                                                      • Interaction of these latter domains with still other transcription factors helps a homeodomain-protein recognize specific enhancers in the DNA.
                                                      • In Drosophila, different combinations of homeobox genes are active in different parts of the embryo and at different times, leading to pattern formation.
                                                      • These include numerous genes encoding components of signaling pathways.
                                                      • In some cases, small changes in regulatory sequences of particular genes can lead to major changes in body form.
                                                      • For example, varying expression of the Hox genes along the body axis produce different numbers of leg-bearing segments in insects and crustaceans.
                                                      • However, they do not appear to function as master regulatory switches in plants.
                                                      • Other genes appear to be responsible for pattern formation in plants.

                                                      There are some basic similarities—and many differences—in the development of plants and animals.

                                                      • The last common ancestor of plants and animals was a single-celled microbe living hundreds of millions of years ago, so the processes of development evolved independently in the two lineages.
                                                        • Plants have rigid cell walls that prevent cell movement, while morphogenetic movements are very important in animals.
                                                        • Morphogenesis in plants is dependent on differing planes of cell division and selective cell enlargement.
                                                        • In both plants and animals, development relies on a cascade of transcriptional regulators turning on or off genes in a finely tuned series.
                                                        • Quite a few of the master regulatory switches in Drosophila are homeobox-containing Hox genes.
                                                        • Those in Arabidopsis belong to the Mads-box family of genes.

                                                        Lecture Outline for Campbell/Reece Biology, 7th Edition, © Pearson Education, Inc. 21-1


                                                        Sex Determination in animals.

                                                        There are various mechanisms for sex determination in animals. These include sex chromosomes, chromosome dosage, and environment.

                                                        For example in humans and other mammals XY embryos develop as males while XX embryos become females. This difference in development is due to the presence of only a single gene, the TDF-Y gene, on the Y-chromosome. Its presence and expression dictates that the sex of the individual will be male. Its absence results in a female phenotype.

                                                        Although Drosophila melanogaster also has an XX-XY sex chromosomes, its sex determination system uses a different method, that of X:Autosome (X:A) ratio. In this system it is the ratio of autosome chromosome sets (A) relative to the number of X-chromosomes (X) that determines the sex. Individuals with two autosome sets and two X-chromosomes (2A:2X) will develop as females, while those with only one X-chromosome (2A:1X) will develop as males. The presence/absence of the Y-chromosome and its genes are not significant.

                                                        In other species of animals the number of chromosome sets can determine sex. For example the haploid-diploid system is used in bees, ants, and wasps. Typically haploids are male and diploids are female.

                                                        In other species, the environment can determine an individuals sex. In alligators (and some other reptiles) the temperature of development dictates the sex, while in many reef fish, the population sex ratio can cause some individuals to change sex.


                                                        10 Answers 10

                                                        Preface
                                                        This question is very similar (but not identical) to a previous World Builder question (What is the minimum human population to maintain a colony). If you're interested in this question and answer, I recommend reading that question and its answers for additional information.

                                                        MVP
                                                        The term you are looking for is Minimum Viable Population.

                                                        This term [MVP] is used in the fields of biology, ecology, and conservation biology. More specifically, MVP is the smallest possible size at which a biological population can exist without facing extinction from natural disasters or demographic, environmental, or genetic stochasticity. The term "population" rarely refers to an entire species.

                                                        MVP doesn't normally mean survival of a species but it can be used to calculate this too.

                                                        The reference indicates that without human management, this value averages slightly under 5,000 individuals for terrestrial vertebrates.

                                                        I do recall reading that you can make smaller numbers viable through human intervention. The following is my recollection. I no longer remember the reference I got the numbers from.

                                                        At 5000 individuals
                                                        Population is viable without human intervention.

                                                        At 500 individuals
                                                        Couples can remain monogamous but mating pairs must be approved by a genetics board to ensure genetic diversity and limit in-breeding.

                                                        At 50 individuals
                                                        Each individual must have as many babies with different partners as possible over their lifetime.

                                                        A genetics board must approve all matings. Couples may pair, but each couple could only conceive one child. Individuals that had paired would still have to mate outside their relationship until the size of the population grew larger and more diverse (probably not possible for several generations).

                                                        It looked like 50 was the absolute minimum and that if you lost very many members early (due to accident or disease) it would endanger the whole colony.

                                                        Another opinion:
                                                        A geneticist actually studied a related question, which was "what is the optimal crew size for a generation ship". The "optimum" was considered the smallest crew that maintained acceptable genetic diversity (I don't know what he deemed acceptable) during the ship's 200 year / 10 generation voyage.

                                                        For a space trip of 200 years, perhaps eight to 10 generations, his calculations suggest a minimum number of 160 people are needed to maintain a stable population.

                                                        At the end of this journey, the crew must be reintroduced to a larger population with greater genetic diversity (a large destination population or fertilized egg bank to ensure genetic problems don't crop up. The article doesn't explicitly state this but it implies that without introducing this diversity, the effects of in-breeding might be large.

                                                        "The decrease in genetic variation is actually quite small and less than found in some successful small populations on Earth," he says. "It would not be a significant factor as long as the space travellers come home or interact with other humans at the end of the 200 year period."

                                                        For this question, we have to consider that these numbers are lower than the minimum required to repopulate the planet because to repopulate the planet, our population will start with all the genetic diversity it is ever going to get.

                                                        As others have suggested, you get better diversity if you hand pick the members for that diversity rather than depending upon chance. The 160 people number above considers that the members of that population were selected for diversity.

                                                        Also note that the person creating this population could use the opportunity to concentrate perceived positive traits in humans. However, many positive traits (e.g. one of the 1000 genes affecting intelligence) often carry hidden or recessive negative traits with them. The gene screening would need to be done most carefully to avoid concentrating genes which when combined cause major negative side-effects.

                                                        People have reported, based on genetic bottleneck studies, that last time it may have been around 10000 people. Maybe not Toba's fault, but bottlenecks are part of our history. The amount of variation can be inferred, but it's hard to say how many people that means since we suppose that they were more diverse before that. Current humans might need many more individuals to achieve the same amount of diversity. If the survivors were the population of Queens NY, a small number would do. If they were an isolated village, the whole village is not enough.

                                                        The results are consistent with a founding population that includes' 70 women (between 50 and 100)

                                                        This doesn't give a minimum, but it does show a low number that worked.

                                                        Let's do some actual math to try and estimate things. First, some basic genetics. Each founding member of your population brings with them 2 copies of each of their chromosomes. There are many thousands of genes on each of these chromosomes, and the vast majority of them all work perfectly in each of us. But, due to random mutations, some people have copies of genes that don't work. Often times this is fine, because you have only one broken copy, and your other copy works and is able to compensate for the broken allele. Geneticists call this haplosufficiency. What this means is that the broken gene, or bad allele, is recessive, while the working gene, or good allele, is dominant. The bad allele only causes an issue in individuals that get two broken copies. If you have one broken copy and one working copy you are heterozygous at that locus, and you are a carrier for the disease. If you have two broken copies you are homozygous for the disease and will be affected by it.

                                                        Most bad alleles are rare, because they are selected against by natural selection. A carrier for a disease gene is only at risk of having a child with the disease if they happen to mate with another carrier of the same disease. This is why inbreeding is bad. When two individuals that are closely related mate, they have a high probability of both being carriers for the same genetic disorders, and therefore of having a child with two copies of the bad allele, and therefore the disease.

                                                        So, math time. I'm going to simplify things a bit for the reader's sake as well as my own, but the results should still be reasonably close to the reality.

                                                        Let's say we begin with a population of size N. That means there will be 2*N total copies of each gene or allele in our gene pool. So if anyone in our starting population of size N is a carrier for a genetic disorder, that genetic disorder will exist within our population at a frequency of 1/(2N). The frequency of the good allele in the population will be 1 - 1/(2N). Let's call these frequencies q and p respectively. Now, there are 3 possible genotypes, or genetic combinations possible. 2 good alleles, 1 good allele and 1 bad allele, and 2 bad alleles. For any randomly shuffled population the probabilities for each of these genotypes are as follows: 2 good alleles = p^2, 1 good and 1 bad allele = 2pq, and 2 bad alleles = q^2. The reasoning behind these numbers should be fairly straightforward. The probability of having 2 bad alleles is equal to frequency of the bad allele squared. Using some simple substitution we now find that the frequency of a genetic disorder which was brought into the population will be (1/(2N))^2.

                                                        Let's try our formula out with an actual example. Let's say we have a starting population of 10. One of our 10 people happens to carry a mutation in the CFTR gene, meaning they are a carrier of Cystic Fibrosis. This means that 1/20 of all of the CFTR genes in our gene pool are broken. The chances of a child in the population receiving 2 copies of the broken CFTR gene and thereby having Cystic Fibrosis is 1/20 * 1/20 or 1/400 or 0.25%. Now, this doesn't sound all that bad right? The problem is that your starting population would be very lucky if it only had 1 carrier for 1 genetic disorder in it. A very recent paper estimated that the average person is a carrier for 1-2 recessive lethal mutations: http://www.genetics.org/content/199/4/1243.full. If each person in our starting population was a carrier for a single different recessive lethal genetic disorder, then each of those 10 diseases would kill

                                                        0.25% of our future population (slightly less because sometimes they would co-occur).

                                                        Let's make things worse and say we only had a starting population of 2. If each of those individuals were a carrier for a single recessive lethal mutation then those bad alleles would exist in the population at a frequency of 25% and children would get 2 bad copies 6.25% of the time. With two diseases that means roughly one eight of the children would die from genetic defects.

                                                        Let's make things better and say we had a starting population of 100, each of whom bring in 1 recessive lethal allele. Each of these 100 diseases would now only occur 0.0025% of the time for a total of 0.25% child death.

                                                        However, this is only taking into account lethal mutations. There are likely many more mutations that could cause infertility, intellectual disability, and numerous other problems. I can't find any numbers on how many of these types of mutations the average person is a carrier for, but it's likely higher than the number for recessive lethal mutations as the selection against them would not be as strong.

                                                        A few extra notes. First, these inbreeding effects will gradually decline over time. Each time a child is born with 2 bad copies of a gene and dies, those 2 bad copies are removed from the gene pool. The worse the frequency of the genetic disorders are, the faster the frequencies of the bad alleles will decrease in the population. Second, the starting population size will also determine how many generations it takes before the population is sufficiently mixed that inbreeding even begins to occur. In a starting population of 2, the first generation will need to inbreed, but in the population size of 100, many generations would go by before anyone needed to procreate with someone at all related to them. Third, when the starting population size is small the outcome will also be highly variable. The numbers I calculated above represent the average outcome assuming the population gets neither lucky nor unlucky in which alleles get passed on to the next generation, but with a small starting population size a few unlucky inheritances of bad alleles could have disastrous complications later on, whereas some lucky inheritances of good alleles could remove all the bad alleles from the population early on. Small populations would also have a high degree of chance in how bad the inbreeding becomes.

                                                        While I didn't really provide you with a concrete number, I hope the mathematics will allow you to calculate your own starting population size given your definition of "relatively clean".


                                                        Hypothesis Testing

                                                        Biologists study the living world by posing questions about it and seeking science-based responses. This approach is common to other sciences as well and is often referred to as the scientific method. The scientific method was used even in ancient times, but it was first documented by England’s Sir Francis Bacon (1561–1626), who set up inductive methods for scientific inquiry. The scientific method is not exclusively used by biologists but can be applied to almost anything as a logical problem-solving method.

                                                        Figure1.17 Sir Francis Bacon is credited with being the first to document the scientific method.

                                                        The scientific process typically starts with an observation (often a problem to be solved) that leads to a question. Let’s think about a simple problem that starts with an observation and apply the scientific method to solve the problem. One Monday morning, a student arrives at class and quickly discovers that the classroom is too warm. That is an observation that also describes a problem: the classroom is too warm. The student then asks a question: “Why is the classroom so warm?”

                                                        Recall that a hypothesis is a suggested explanation that can be tested. To solve a problem, several hypotheses may be proposed. For example, one hypothesis might be, “The classroom is warm because no one turned on the air conditioning.” But there could be other responses to the question, and therefore other hypotheses may be proposed. A second hypothesis might be, “The classroom is warm because there is a power failure, and so the air conditioning doesn’t work.”

                                                        Once a hypothesis has been selected, a prediction may be made. A prediction is similar to a hypothesis but it typically has the format “If . . . then . . . .” For example, the prediction for the first hypothesis might be, “If the student turns on the air conditioning, then the classroom will no longer be too warm.”

                                                        A hypothesis must be testable to ensure that it is valid. For example, a hypothesis that depends on what a bear thinks is not testable, because it can never be known what a bear thinks. It should also be falsifiable, meaning that it can be disproven by experimental results. An example of an unfalsifiable hypothesis is “Botticelli’s Birth of Venus is beautiful.” There is no experiment that might show this statement to be false. To test a hypothesis, a researcher will conduct one or more experiments designed to eliminate one or more of the hypotheses. This is important. A hypothesis can be disproven, or eliminated, but it can never be proven. Science does not deal in proofs like mathematics. If an experiment fails to disprove a hypothesis, then we find support for that explanation, but this is not to say that down the road a better explanation will not be found, or a more carefully designed experiment will be found to falsify the hypothesis.

                                                        Each experiment will have one or more variables and one or more controls. A variable is any part of the experiment that can vary or change during the experiment. A control is a part of the experiment that does not change. Look for the variables and controls in the example that follows. As a simple example, an experiment might be conducted to test the hypothesis that phosphate limits the growth of algae in freshwater ponds. A series of artificial ponds are filled with water and half of them are treated by adding phosphate each week, while the other half are treated by adding a salt that is known not to be used by algae. The variable here is the phosphate (or lack of phosphate), the experimental or treatment cases are the ponds with added phosphate and the control ponds are those with something inert added, such as the salt. Just adding something is also a control against the possibility that adding extra matter to the pond has an effect. If the treated ponds show lesser growth of algae, then we have found support for our hypothesis. If they do not, then we reject our hypothesis. Be aware that rejecting one hypothesis does not determine whether or not the other hypotheses can be accepted it simply eliminates one hypothesis that is not valid . Using the scientific method, the hypotheses that are inconsistent with experimental data are rejected.

                                                        Figure 1.18 The scientific method is a series of defined steps that include experiments and careful observation. If a hypothesis is not supported by data, a new hypothesis can be proposed.

                                                        In the example below, the scientific method is used to solve an everyday problem. Which part in the example below is the hypothesis? Which is the prediction? Based on the results of the experiment, is the hypothesis supported? If it is not supported, propose some alternative hypotheses.

                                                        1. My toaster doesn’t toast my bread.
                                                        2. Why doesn’t my toaster work?
                                                        3. There is something wrong with the electrical outlet.
                                                        4. If something is wrong with the outlet, my coffeemaker also won’t work when plugged into it.
                                                        5. I plug my coffeemaker into the outlet.
                                                        6. My coffeemaker works.

                                                        In practice, the scientific method is not as rigid and structured as it might at first appear. Sometimes an experiment leads to conclusions that favour a change in approach often, an experiment brings entirely new scientific questions to the puzzle. Many times, science does not operate in a linear fashion instead, scientists continually draw inferences and make generalizations, finding patterns as their research proceeds. Scientific reasoning is more complex than the scientific method alone suggests.

                                                        Watch a video about the progress of science.


                                                        Mendel&rsquos Law of Inheritance | Genetics

                                                        Gregor Johann Mendel conducted hybridisation experiments on garden pea (Pisum sativum) for seven years (1856-1863) and proposed the laws of inheritance in living organisms. He is also known as Father of Genetics.

                                                        Mendel Experimental Material:

                                                        He selected garden pea plant as a sample for following reasons:

                                                        (i) Pea is available in many varieties on a large scale to observe alternate traits.

                                                        (ii) Peas are self-pollinated and can be cross-pollinated also to prevent self-pollination.

                                                        (iii) These are annual plants with a short life cycle. So, several generations can be studied within a short period.

                                                        (iv) Pea plants could easily be raised, maintained and handled.

                                                        (v) Many varieties are available with distinct characteristics. Which plants provide many easily detectable contrasting characters.

                                                        Mendel conducted artificial pollination/cross-pollination experiments using several true-breeding pea lines. A true-breeding line refers to one that have undergone continuous self-pollination and showed stable trait inheritance and expression for several generations. Mendel selected 14 true-breeding pea plant varieties, as pair, which were similar except for one character with contrasting traits.

                                                        A List of Contrasting Traits studied by Mendel in Pea Plant

                                                        Mendel’s Procedure:

                                                        (i) Mendel observed one trait at a time. For example, he crossed tall and dwarf pea plants to study the inheritance of one gene.

                                                        (ii) He hybridised plants with alternate forms of a single trait (monohybrid cross). The seeds produced by this cross were grown to develop into plants of Fillial1 progeny or F1-generation (F1-plants).

                                                        (iii) He then self-pollinated the tall F1 -plants to produce plants of Fillial2 progeny or F1-generation.

                                                        (iv) In later experiments, Mendel also crossed pea plants with two contrasting characters known as dihybrid cross.

                                                        Mendel’s Observations:

                                                        (i) In F1generation, Mendel found that all pea plants were tall and none was dwarf.

                                                        (ii) He also observed other pair of traits and found that F1 always resembled either one of its parents and the traits of other parent was not found in this generation.

                                                        (iii) In F2-generation, he found that some of the offsprings were ‘dwarf, i.e., the character which were not seen in F1-generation was expressed in F2.

                                                        (iv) These contrasting traits (tall/dwarf) did not show any mixing either in F1 or in F2-generation.

                                                        (v) Similar results were obtained with the other traits that he studied. Only one of the parental traits was expressed in F1-generation, while at F2 stage, both the traits were expressed in the ratio of 3:1.

                                                        (vi) Mendel also found identical results in dihybrid cross as in monohybrid cross.

                                                        (vii) The trait that appeared in the F1 is called dominant trait, while the other trait is recessive trait.

                                                        (viii) In tall/dwarf traits, tallness is dominant over dwarfness that is recessive.

                                                        Mendel’s Inferences:

                                                        Following inferences were made by Mendel based on his observations:

                                                        (i) He proposed that some factors pass down from parent to offsprings through the gametes. Now-a-days these factors are known as genes.

                                                        (a) Genes are hence, the units of inheritance.

                                                        (b) Genes which code for a pair of contrasting traits are known as alleles, i.e., they are slightly different forms of the same gene.

                                                        (ii) Genes occur in pairs in which, one dominates the other called dominant factor and expresses itself, while the other remains hidden and is recessive.

                                                        (iii) Allele can be similar in case of homozygote TT or tt and dissimilar in case of heterozygote Tt.

                                                        (iv) In a true-breeding tall or dwarf pea variety, the allelic pair of genes for height are identical or homozygous.

                                                        (v) TT and tt are called genotype of the plant, while the term tall and dwarf are the phenotype.

                                                        (vi) When the tall and the dwarf plant produce gametes by the process of meiosis, the alleles of the parental pair segregate and only one of the allele gets transmitted to a gamete.

                                                        Thus, there is only a 50% chance of a gamete containing either allele, as the segregation is a random process.

                                                        (vii) During fertilisation, the two alleles, T from one parent and t from other parent are united to produce zygote, that has one T and one t allele or the hybrids have Tt.

                                                        (viii) Since, these hybrids contain alleles which express contrasting traits, the plants are heterozygous.

                                                        Punnett Square:

                                                        It is a graphical representation to calculate the probability of all possible genotypes of off springs in a genetic cross (Fig.5.2). The production of gametes by the parents, the formation of zygote, the F1 and F2 – germinations can be explained by Punnett square. It was developed by British geneticist RC Punnett.

                                                        Mendel’s Law:

                                                        Mendel’s laws of inheritance are based on his observations on monohybrid crosses.

                                                        He proposed the following laws of inheritance:

                                                        1. Law of Dominance (First Law):

                                                        The law of dominance states that when two alternative forms of a trait or character (genes) are present in an organism, only one factor expresses itself in F1-progeny and is called dominant, while the other that remains masked is called recessive.

                                                        This law is used to explain the expression of only one of the parental characters in a monohybrid cross in the F1 -generation and the expression of both in the F2-generation. It also explains the proportion of 3:1 obtained in theF2-generation.

                                                        2. Law of Segregation (Second Law):

                                                        This law states that the alleles do not show any blending and both the characters are recovered as such in the F2-generation, though one of these is not seen in the F1 -generation.

                                                        Due to this, the gametes are pure for a character. The parents contain two alleles during gamete formation.

                                                        The factors or alleles of a pair segregate from each other such that a gamete receives only one of the two factors.

                                                        3. Law of Independent Assortment (Third Law):

                                                        This law states that when two pairs of traits are combined in a hybrid, segregation of one pair of character is independent of the other pair of characters at the time of gamete formation.

                                                        It also get randomly rearranged in the offsprings producing both parental and new combinations of characters. The law was proposed by Mendel, based on the results of dihybrid crosses, where inheritance of two traits were considered simultaneously.


                                                        15.1 The Genetic Code

                                                        By the end of this section, you will be able to do the following:

                                                        • Explain the “central dogma” of DNA-protein synthesis
                                                        • Describe the genetic code and how the nucleotide sequence prescribes the amino acid and the protein sequence

                                                        The cellular process of transcription generates messenger RNA (mRNA), a mobile molecular copy of one or more genes with an alphabet of A, C, G, and uracil (U). Translation of the mRNA template on ribosomes converts nucleotide-based genetic information into a protein product. That is the central dogma of DNA-protein synthesis. Protein sequences consist of 20 commonly occurring amino acids therefore, it can be said that the protein alphabet consists of 20 “letters” (Figure 15.2). Different amino acids have different chemistries (such as acidic versus basic, or polar and nonpolar) and different structural constraints. Variation in amino acid sequence is responsible for the enormous variation in protein structure and function.

                                                        The Central Dogma: DNA Encodes RNA RNA Encodes Protein

                                                        The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma (Figure 15.3), which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis, while keeping the DNA itself intact and protected. The copying of DNA to RNA is relatively straightforward, with one nucleotide being added to the mRNA strand for every nucleotide read in the DNA strand. The translation to protein is a bit more complex because three mRNA nucleotides correspond to one amino acid in the polypeptide sequence. However, the translation to protein is still systematic and colinear , such that nucleotides 1 to 3 correspond to amino acid 1, nucleotides 4 to 6 correspond to amino acid 2, and so on.

                                                        The Genetic Code Is Degenerate and Universal

                                                        Each amino acid is defined by a three-nucleotide sequence called the triplet codon. Given the different numbers of “letters” in the mRNA and protein “alphabets,” scientists theorized that single amino acids must be represented by combinations of nucleotides. Nucleotide doublets would not be sufficient to specify every amino acid because there are only 16 possible two-nucleotide combinations (4 2 ). In contrast, there are 64 possible nucleotide triplets (4 3 ), which is far more than the number of amino acids. Scientists theorized that amino acids were encoded by nucleotide triplets and that the genetic code was “degenerate.” In other words, a given amino acid could be encoded by more than one nucleotide triplet. This was later confirmed experimentally: Francis Crick and Sydney Brenner used the chemical mutagen proflavin to insert one, two, or three nucleotides into the gene of a virus. When one or two nucleotides were inserted, the normal proteins were not produced. When three nucleotides were inserted, the protein was synthesized and functional. This demonstrated that the amino acids must be specified by groups of three nucleotides. These nucleotide triplets are called codons . The insertion of one or two nucleotides completely changed the triplet reading frame , thereby altering the message for every subsequent amino acid (Figure 15.5). Though insertion of three nucleotides caused an extra amino acid to be inserted during translation, the integrity of the rest of the protein was maintained.

                                                        Scientists painstakingly solved the genetic code by translating synthetic mRNAs in vitro and sequencing the proteins they specified (Figure 15.4).

                                                        In addition to codons that instruct the addition of a specific amino acid to a polypeptide chain, three of the 64 codons terminate protein synthesis and release the polypeptide from the translation machinery. These triplets are called nonsense codons , or stop codons. Another codon, AUG, also has a special function. In addition to specifying the amino acid methionine, it also serves as the start codon to initiate translation. The reading frame for translation is set by the AUG start codon near the 5' end of the mRNA. Following the start codon, the mRNA is read in groups of three until a stop codon is encountered.

                                                        The arrangement of the coding table reveals the structure of the code. There are sixteen "blocks" of codons, each specified by the first and second nucleotides of the codons within the block, e.g., the "AC*" block that corresponds to the amino acid threonine (Thr). Some blocks are divided into a pyrimidine half, in which the codon ends with U or C, and a purine half, in which the codon ends with A or G. Some amino acids get a whole block of four codons, like alanine (Ala), threonine (Thr) and proline (Pro). Some get the pyrimidine half of their block, like histidine (His) and asparagine (Asn). Others get the purine half of their block, like glutamate (Glu) and lysine (Lys). Note that some amino acids get a block and a half-block for a total of six codons.

                                                        The specification of a single amino acid by multiple similar codons is called "degeneracy." Degeneracy is believed to be a cellular mechanism to reduce the negative impact of random mutations. Codons that specify the same amino acid typically only differ by one nucleotide. In addition, amino acids with chemically similar side chains are encoded by similar codons. For example, aspartate (Asp) and glutamate (Glu), which occupy the GA* block, are both negatively charged. This nuance of the genetic code ensures that a single-nucleotide substitution mutation might specify the same amino acid but have no effect or specify a similar amino acid, preventing the protein from being rendered completely nonfunctional.

                                                        The genetic code is nearly universal. With a few minor exceptions, virtually all species use the same genetic code for protein synthesis. Conservation of codons means that a purified mRNA encoding the globin protein in horses could be transferred to a tulip cell, and the tulip would synthesize horse globin. That there is only one genetic code is powerful evidence that all of life on Earth shares a common origin, especially considering that there are about 10 84 possible combinations of 20 amino acids and 64 triplet codons.

                                                        Link to Learning

                                                        Transcribe a gene and translate it to protein using complementary pairing and the genetic code at this site.


                                                        Do your genes determine your entire life?

                                                        W henever you read stories about identical twins separated at birth, they tend to follow the template set by the most remarkable of them all: the “two Jims”. James Springer and James Lewis were separated as one-month-olds, adopted by different families and reunited at age 39. When University of Minnesota psychologist Thomas Bouchard met them in 1979, he found, as a Washington Post article put it, both had “married and divorced a woman named Linda and remarried a Betty. They shared interests in mechanical drawing and carpentry their favourite school subject had been maths, their least favourite, spelling. They smoked and drank the same amount and got headaches at the same time of day.” The similarities were uncanny. A great deal of who they would turn out to be appears to have been written in their genes.

                                                        Other studies at the world-leading Minnesota Center for Twin and Family Research suggest that many of our traits are more than 50% inherited, including obedience to authority, vulnerability to stress, and risk-seeking. Researchers have even suggested that when it comes to issues such as religion and politics, our choices are much more determined by our genes than we think.

                                                        Many find this disturbing. The idea that unconscious biological forces drive our beliefs and actions would seem to pose a real threat to our free will. We like to think that we make choices on the basis of our own conscious deliberations. But isn’t all that thinking things over irrelevant if our final decision was already written in our genetic code? And doesn’t the whole edifice of personal responsibility collapse if we accept that “my genes made me do it”? To address these concerns, we first need to look a bit more closely at what the experiences of identical twins really show.

                                                        Professor Tim Spector has been studying identical twins at King’s College London for more than 20 years. From the start of his research in the early 1990s, it became evident to Spector that identical twins were always more similar than brothers or sisters or non-identical twins. At the time, however, “social scientists hated the idea” that genes were an important determinant of who we were, “particularly in those rather controversial areas like IQ, personality and beliefs”. As “one of the many scientists who took the gene-centric view of the universe for granted”, Spector wanted “to prove them wrong, and to prove that there’s nothing that’s not genetic to some extent”. Today, he looks back on this as part of his “overzealous genetic phase”.

                                                        It is perhaps understandable that Spector got caught up in gene mania. The launch in 1990 of the Human Genome Project, which aimed to map the complete sequence of human DNA, came at the beginning of a decade that would mark the high point of optimism about how much our genes could tell us. Daniel Koshland, then editor of the prestigious journal Science, captured the mood when he wrote: “The benefits to science of the genome project are clear. Illnesses such as manic depression, Alzheimer’s, schizophrenia, and heart disease are probably all multigenic and even more difficult to unravel than cystic fibrosis. Yet these diseases are at the root of many current societal problems.” Genes would help us uncover the secrets of all kinds of ills, from the psychological to the physical.

                                                        Ten years later, Bill Clinton and Tony Blair were among the guests gathered to “celebrate the revelation of the first draft of the human book of life”, as Francis Collins, the director of the Human Genome Project, put it. “We try to be cautious on days like this,” said the ABC news anchor, “but this map marks the beginning of an era of discovery that will affect the lives of every human being, with implications for science, history, business, ethics, religion, and, of course, medicine.”

                                                        By that time, genes were no longer simply the key to understanding health: they had become the skeleton key for unlocking almost all the mysteries of human existence. For virtually every aspect of life – criminality, fidelity, political persuasion, religious belief – someone would claim to find a gene for it. In 2005 in Hall County, Georgia, Stephen Mobley tried to avoid execution by claiming that his murder of a Domino’s pizza store manager was the result of a mutation in the monoamine oxidase A (MAOA) gene. The judge turned down the appeal, saying that the law was not ready to accept such evidence. The basic idea, however, that the low-MAOA gene is a major contributing cause of violence has become widely accepted, and it is now commonly called the “warrior gene”.

                                                        In recent years, however, faith in the explanatory power of genes has waned. Today, few scientists believe that there is a simple “gene for” anything. Almost all inherited features or traits are the products of complex interactions of numerous genes. However, the fact that there is no one genetic trigger has not by itself undermined the claim that many of our deepest character traits, dispositions and even opinions are genetically determined. (This worry is only slightly tempered by what we are learning about epigenetics, which shows how many inherited traits only get “switched on” in certain environments. The reason this doesn’t remove all fears is that most of this switching on and off occurs very early in life – either in utero or in early childhood.)

                                                        What might reduce our alarm, however, is an understanding of what genetic studies really show. The key concept here is of heritability. We are often told that many traits are highly heritable: happiness, for instance, is around 50% heritable. Such figures sound very high. But they do not mean what they appear to mean to the statistically untrained eye.

                                                        The common mistake people make is to assume that if, for example, autism is 90% heritable, then 90% of autistic people got the condition from their parents. But heritability is not about “chance or risk of passing it on”, says Spector. “It simply means how much of the variation within a given population is down to genes. Crucially, this will be different according to the environment of that population.

                                                        Spector spells out what this means with something such as IQ, which has a heritability of 70% on average. “If you go to the US, around Harvard, it’s above 90%.” Why? Because people selected to go there tend to come from middle-class families who have offered their children excellent educational opportunities. Having all been given very similar upbringings, almost all the remaining variation is down to genes. In contrast, if you go to the Detroit suburbs, where deprivation and drug addiction are common, the IQ heritability is “close to 0%”, because the environment is having such a strong effect. In general, Spector believes, “Any change in environment has a much greater effect on IQ than genes,” as it does on almost every human characteristic. That’s why if you want to predict whether someone believes in God, it’s more useful to know that they live in Texas than what their genes are.

                                                        Statistical illiteracy is not the only reason why the importance of environmental factors is so often drowned out. We tend to be mesmerised by the similarities between identical twins and notice the differences much less. “When you look at twins,” says Spector, “the one thing that always seems to come out are the subconscious tics, mannerisms, postures, the way they laugh. They sit the same, cross their legs the same, pick up cups of coffee the same, even if they hate each other or they’ve been separated all their lives.” It’s as though we cannot help thinking that such things reflect deeper similarities even though they are actually the most superficial features to compare. If you can stop yourself staring at the similarities between twins, literally and metaphorically, and listen properly to their stories, you can see how their differences are at least as telling as their similarities. Far from proving that our genes determine our lives, these stories show just the opposite.

                                                        When Ann and Judy from Powys, mid-Wales were born in the 1940s, they were the last thing their working-class family with five children needed. So, identical or not, Ann and Judy were packed off to live with different aunts. After three months, Judy returned to her biological mother, as her aunt could not manage raising another child. But for the childless 50-year-old couple who took on Ann (without ever formally adopting her), the late opportunity for parenthood was a blessing and she stayed.

                                                        Ann and Judy, who are now well into retirement, told me their story in Ann’s home in Crickhowell on the edge of the Brecon Beacons, over coffee and home-made Welsh cakes. Their experience is a valuable corrective for anyone who has been impressed by tales of how identical twins show that we are basically nothing but the products of our genes.

                                                        Although the girls grew up in the same town, they ended up living in different areas and went to different schools. The two households in which Ann and Judy grew up were very different. Judy’s father drove trains inside the steelworks, and her mother, like most women at the time, did not have a job. The family lived in a basic two-up, two-down house with a toilet at the bottom of the garden. Judy’s four older brothers were all out working by the time she was five and she was left with her older sister Yvonne.

                                                        Ann was brought up in a newly built, semi-detached house, with a toilet indoors. Her father was also a manual labourer in the steelworks, but they were relatively well off, partly because they hadn’t had children but also because they were “very careful with money”. Ann recalled that “the sugar bowl was never filled so as not to encourage people to take too much”.

                                                        Where Judy told me she “was a street kid, always out”, Ann said she always had her “nose in a book because I was on my own”. And while Ann passed the 11-plus exam and got into the grammar school, Judy didn’t, and ended up at the secondary modern. Although, aged 15, Judy was offered a place at a grammar school, when she got there she found herself suddenly studying algebra and geometry in a class where everyone else had already being doing it for three years. Unsurprisingly she struggled. After four months, Judy quit and went to work in a furniture shop.

                                                        Ann, meanwhile, breezed through school, although she, too, left early because her now 66-year-old father was retiring. “I just felt that it wasn’t fair for me to stay on at school when they were on a pension,” she said. At 16, Ann began her white-collar job in the local council offices, not long after Judy had started working on the shop floor.

                                                        Although the twins’ paths had diverged up to this point, the next stage in the story is the moment where their stories converge in an uncanny way. Less than six months into her job, Ann got pregnant and quit. Two months later, Judy also got pregnant and quit the nursing course she was enrolled in. Not only that, but both fathers, soon husbands, turned out to be very violent.

                                                        However, the differences in what happened next are instructive. Ann didn’t stay married for long. “I left and went back home, and they were very supportive when they found out what was going on.” Judy, in contrast, stayed with her husband for 17 years. “I did leave him, mind, but I kept going back. I didn’t have the support. I had three children by the time I was 21.” Her mother was no help. “My mother’s attitude was, you made your bed, you lie on it,” Judy explained. Ann understands Judy’s acquiescence perfectly. “Imagine being at home, with three children, no qualifications, nothing on the horizon to see your life was going to get better, which I did have.”

                                                        The two only really started a proper sibling relationship after Ann read about the Minnesota University research in the paper and wrote to the university about her and her sister. When they were 48, they travelled together to Minnesota to meet scientists there. Now the twins are both retired. Judy says, “I think from where we started we’ve travelled the same distance.”

                                                        But there were important differences in how their lives went, and so too in the people they became. Most obviously, Ann has always had more money, but you can also see the effects of their different backgrounds on their health. “Judy’s had a hysterectomy, I haven’t,” says Ann. “Judy’s got a problem with her kidneys. I don’t. Judy’s got blood pressure, I haven’t. But she’s stronger than me.”

                                                        There are also differences in how they think and behave socially. Although their political views are very similar, Judy says, “I’m a Christian, well, probably agnostic, I think,” whereas Ann is “a confirmed atheist”. Ann also thinks she’s “much more diplomatic. Judy is just rude. That’s probably the educational background coming through. ‘Interfering’ is too strong a word, but Judy is more involved with her children and grandchildren in an advisory capacity, whereas I wouldn’t do that.” Much of this, they agree, is surely down to culture, with Ann being encouraged to adopt more genteel middle-class ways.

                                                        Ann and Judy’s story illustrates that our genes only set down what might be described as a field of possibilities. These set limits on what we are to become – so whatever our upbringings, most of us will tend towards introversion or extroversion, jollity or sobriety, facility with words or numbers. But this is far from the claim that we become is essentially written in our genes. Rather, various options are pencilled in, and our life experiences determine which get inked.

                                                        Tim Spector’s view that environment is almost always more influential than genes is clear in the case of Ann and Judy. The sisters shared the same genes but with a middle-class background Ann did better at school, earned more money and has enjoyed better health. Too much attention to genes blinds us to the obvious truth that access to financial and educational resources remains the most important determinant of how we fare in life.

                                                        Although being more middle class might improve your odds of success in life, other non-genetic factors play a huge role. Take the war babies Margaret and Eileen from Preston, Lancashire, another set of identical twins who were brought up in different families. Margaret’s adoptive parents owned their own house. Eileen’s toilet was at the bottom of the garden. And yet it was Margaret who flunked her 11-plus, simply out of nerves, while Eileen passed hers. Margaret’s adoptive mother was “hard”, and when her daughter passed her 11-plus on the second attempt she said she couldn’t go to the grammar school anyway because she had already bought the uniform for the other school. As Margaret says to Eileen now, “Your mum told you you were loved and you had to be adopted. My mum never said that. I remember waking up when I was eight years old and thinking, somebody had me and they didn’t want me. It’s horrifying, really traumatic for an eight-year-old.”

                                                        Eileen agrees that she came out better when it came to love and affection. “My mother always said Ellen [the twins’ birth mother] was very good to give me to her. She always pointed that out, and they picked me because they wanted me. I was secure despite the fact that I had to go and live in this tatty bungalow.”

                                                        Professor Tim Spector Photograph: Orion Books

                                                        Another difference in how their lives have progressed has been their choice of husbands. “You’ve been further afield than I have,” says Eileen to Margaret, turning to me and adding, “I think she’s more or less finished her bucket list. My husband won’t go. He’s not interested in travel. I’ve had to drag him out of the country.”

                                                        Identical twins show us that in the nature-versus-nurture debate, there is no winner. Both have their role to play in shaping who we are. But although we have reason to doubt that our genes determine our lives in some absolute way, this does not solve a bigger worry about whether or not we have free will.

                                                        Who we are appears to be a product of both nature and nurture, in whatever proportion they contribute, and nothing else. You are shaped by forces beyond yourself, and do not choose what you become. And so when you go on to make the choices in life that really matter, you do so on the basis of beliefs, values and dispositions that you did not choose.

                                                        Although this may appear troubling, it is hard to see how it could be any other way. For example, say you support a more redistributive tax system, because you think that is fair. Where did that sense of fairness come from? You may well have thought it through and come to a conclusion. But what did you bring to that process? A combination of abilities and dispositions that you were born with, and information and thinking skills that you acquired. In other words, a combination of hereditary factors and environment. There is no third place for anything else to come from. You are not responsible for how you emerged from the womb, nor for the world you found yourself in. Once you became old enough and sufficiently self-aware to think for yourself, the key determinants in your personality and outlook were already set. Yes, your views might be changed later in life by powerful experiences or persuasive books. But again, you do not choose for these things to change you. The very way we speak about such experiences suggests this. “This book changed my life,” we say, not “I changed my life with this book”, acknowledging that having read it, we did not choose to be different we simply could never be the same again.

                                                        The literature on free will tends to focus on moments of choice: was I free at that point to do other than what I did? When we ask this, it often seems to us that only one option was viable. Sometimes this is because we think circumstances constrain us. But perhaps a more fundamental reason why at the moment of choice we cannot do otherwise is that we cannot be other than who we are. The nature of the chooser is the key determinant at the moment of choice: who we are comes first and what we do follows.

                                                        To be considered truly free, then, it would seem to be necessary for us to be in some sense responsible for being the people we are, and that responsibility needs to go “all the way down”: it has to be up to you and you alone what values and beliefs you hold dear and act upon. If we are not responsible for who we are, how can we be held responsible for what we do? But when we consider the dual roles of nature and nurture, the values we hold and beliefs we assert do not appear to be a matter of choice. We are formed by forces ultimately beyond our control. This thought, once made explicit, leads many to the conclusion that free will and responsibility are impossible. If you dig deep enough into what made us who we are, eventually you come across some key formative factors that we did not control. And if they are beyond our control, how can we be responsible for them?

                                                        On reflection, though, we ought to be more sanguine about not having complete control. The first step towards acceptance is to realise that it would be a very odd person whose actions did not in some sense flow from her values and beliefs. And yet the more strongly we hold these, the less we really feel free to choose other than the way we do. In 1521, the Reformation priest Martin Luther, for example, is reported to have told those who accused him of heresy at the Diet of Worms, “Here I stand. I can do no other.” This is not a denial of his freedom but an assertion of his freedom to act according to his values.

                                                        We cannot change our characters on a whim, and we would probably not want it any other way. A committed Christian does not want the freedom to wake up one day and become a Muslim. A family man does not want to find it as easy to run off with the au pair as to stick with his children and their mother. A fan of Shostakovich does not, usually at least, wish she could just decide to prefer Andrew Lloyd Webber. The critical point is that these key commitments don’t strike us primarily as choices. You don’t choose what you think is great, who you should love, or what is just. To think of these fundamental life commitments as choices is rather peculiar, perhaps a distortion created by the contemporary emphasis on choice as being at the heart of freedom.

                                                        What’s more, the idea that any kind of rational creature could choose its own basic dispositions and values is incoherent. For on what basis could such a choice be made? Without any values or dispositions, one would have no reason to prefer some over others. Imagine the anteroom in heaven, where people wait to be prepared for life on Earth. Some angel asks you, would you like to be a Republican or a Democrat? How could you answer if you did not already have some commitments and values that would tip the balance either way? It would be impossible.

                                                        Throughout human history, people have had no problem with the idea that their basic personality types were there from birth. The idea of taking after your parents is an almost universal cultural constant. Discovering just how much nature and nurture contribute to who we are is interesting, but doesn’t change the fact that traits are not chosen, and that no one ever thought they were.

                                                        Accepting this is ultimately more honest and liberating than denying it. Recognising how much our beliefs and commitments are shaped by factors beyond our control actually helps us to gain more control of them. It allows us to question our sense that something is obviously true by provoking us to ask whether it would appear so obvious if our upbringing or character had been different. It is only by recognising how much is not in our power that we can seize control of that which is. Perhaps most importantly, accepting how much belief is the product of an unchosen past should help us to be less dogmatic and more understanding of others. It doesn’t mean anything goes, of course, or that no view is right or wrong. But it does mean that no one is able to be perfectly objective, and so we should humbly accept that although objective truth is worth striving for, none of us could claim to have fully attained it.

                                                        Some may not be convinced yet that we should be so relaxed about our debt to nature and nurture. Unless we are fully responsible, it might seem unjust to blame people for their actions. If this seems persuasive, it is only because it rests on the false assumption that the only possible form of real responsibility is ultimate responsibility: that everything about who you are, what you believe and how you act is the result of your free choices alone. But our everyday notion of responsibility certainly does not and could not entail being ultimately responsible in this way. This is most evident in cases of negligence. Imagine you postpone maintaining a roof properly and it collapses during an exceptionally fierce storm, killing or injuring people below. The roof would not have collapsed if there had not been a storm, and the weather is clearly not in your control. But that does not mean you should not be held responsible for failing to maintain the building properly.

                                                        If the only real responsibility were ultimate responsibility, then there could never be any responsibility at all, because everything that happens involves factors both within and outside of our control. As the philosopher John Martin Fischer succinctly and accurately puts it, “Total control is a total fantasy – metaphysical megalomania.”

                                                        Many arguments that purport to debunk free will are powerful only if you buy into the premise that real responsibility is ultimate responsibility. Almost all those who deny free will define responsibility as though it must be total and absolute, or it is nothing at all. The Dutch neuroscientist Dick Swaab, who calls free will “an illusion”, does so by endorsing the definition of free will by Joseph L Price (a scientist, not a philosopher) as “the ability to choose to act or refrain from action without extrinsic or intrinsic constraints”. No wonder he is forced to conclude that, “Our current knowledge of neurobiology makes it clear that there is no such thing as absolute freedom.” Similarly, he claims that the existence of unconscious decision-making in the brain leaves “no room for a purely conscious, free will”. That’s true. The only question is why one would believe such absolute or pure freedom is possible or necessary.

                                                        The answer would appear to be to justify eternal damnation. As Augustine put it in the fourth century, “The very fact that anyone who uses free will to sin is divinely punished shows that free will was given to enable human beings to live rightly, for such punishment would be unjust if free will had been given both for living rightly and for sinning.” If the buck doesn’t stop with us, then it can only stop with the one who created us, making God ultimately responsible for our wickedness. Hence, as Erasmus put it, free will is theologically necessary “to allow the ungodly, who have deliberately fallen short of the grace of God, to be deservedly condemned to clear God of the false accusation of cruelty and injustice to free us from despair, protect us from complacency, and spur us on to moral endeavour.”

                                                        The ultimate punishment requires an ultimate responsibility which cannot exist. That is why we should not be worried to discover that factors outside our control, such as our genetic makeup, are critical to making us the people we have become. The only forms of freedom and responsibility that are both possible and worth having are those that are partial, not absolute. There is nothing science tells us that rules out this kind of free will. We know people are responsive to reasons. We know we have varying capacities of self-control which can be strengthened or weakened. We know there is a difference between doing something under coercion or because you decide yourself you want to. Real free will, not a philosopher’s fantasy, requires no more than these kinds of abilities to direct our own actions. It does not require the impossible feat of having written our own genetic code before we were even born.

                                                        If we become accustomed to thinking of freedom as completely unfettered, anything more limited will at first sight look like an emaciated form of liberty. You might even dismiss it as mere wiggle room: the ability to make limited choices within a framework of great restraint. But that would be a mistake. Unfettered freedom is not only an illusion it makes no sense. It would not be desirable even if we could have it. Quite simply, the commonplace idea of free will we must ditch was always wrong. Good riddance to it.


                                                        Advances in whole genome methylomic sequencing

                                                        Jessica Nordlund , in Epigenetics Methods , 2020

                                                        Abstract

                                                        The remarkable advances in high throughput sequencing have brought unprecedented progression to the field of epigenomic research, particularly in the area of genome-wide DNA methylation analysis. The variety of approaches available have enabled genome-wide profiling of countless cell types and states, resulting in findings that have proved instrumental for advancing our understanding of cellular identity in development, health, and disease. The methylome-wide approaches that are available today vary in many aspects, such as required DNA input, degree of genomic resolution and coverage, and ability of quantification. This chapter discusses the historical development, proven modifications, and the many applications for analysis of DNA methylation and other base modifications on a global scale, as well as their translational potential.