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Amongst silent, nonsense and missense genetic mutations, is the latter the only one that leads to the creation of new alleles?
If we define alleles as a specific form of a gene, and a gene as a heritable factor consisting of a length of DNA that influences a certain characteristic, since the missense mutation is the only one that leads to the physical creation of a new protein, is it not the only one that would lead to the creation of new alleles?
Or would nonsense also lead to new alleles as the lack of the protein may lead to the expression of a different characteristic?
So the term allele is a broad one, and simply refers to the different versions of any piece of DNA in circulation in the gene pool - it doesn't need to refer to a gene. I can talk about the alleles at a random place in the genome.
But if we proceed with your question and ask - 'do nonsense mutations within coding genes also lead to the creation of different proteins' - the answer is 'sometimes'. A nonsense mutation is just one that introduces a stop codon. The result is an mRNA that codes for a shortened protein. Sometimes, the mRNA will be recognized as faulty and degraded, and so little to no protein gets made. Sometimes, if made, that protein will be unstable, or the result will be as if no protein had been made. Sometimes though, the protein will be stable, and could hang around uselessly, or even do damage.
Allele is just a variant form of gene: independent of the final product of protein, so nonsense will also lead to new allele. I will quote Nature Scitable here:
Alleles can also refer to minor DNA sequence variations between alleles that do not necessarily influence the gene's phenotype.
INS-gene mutations: from genetics and beta cell biology to clinical disease
A growing list of insulin gene mutations causing a new form of monogenic diabetes has drawn increasing attention over the past seven years. The mutations have been identified in the untranslated regions of the insulin gene as well as the coding sequence of preproinsulin including within the signal peptide, insulin B-chain, C-peptide, insulin A-chain, and the proteolytic cleavage sites both for signal peptidase and the prohormone convertases. These mutations affect a variety of different steps of insulin biosynthesis in pancreatic beta cells. Importantly, although many of these mutations cause proinsulin misfolding with early onset autosomal dominant diabetes, some of the mutant alleles appear to engage different cellular and molecular mechanisms that underlie beta cell failure and diabetes. In this article, we review the most recent advances in the field and discuss challenges as well as potential strategies to prevent/delay the development and progression of autosomal dominant diabetes caused by INS-gene mutations. It is worth noting that although diabetes caused by INS gene mutations is rare, increasing evidence suggests that defects in the pathway of insulin biosynthesis may also be involved in the progression of more common types of diabetes. Collectively, the (pre)proinsulin mutants provide insightful molecular models to better understand the pathogenesis of all forms of diabetes in which preproinsulin processing defects, proinsulin misfolding, and ER stress are involved.
Keywords: Diabetes Endoplasmic reticulum stress Insulin biosynthesis Insulin gene mutation Pancreatic beta cell Proinsulin misfolding.
Copyright © 2014 Elsevier Ltd. All rights reserved.
The effects of INS -gene…
The effects of INS -gene mutations on the major steps of insulin biosynthesis.…
Three functional regions of preproinsulin…
Three functional regions of preproinsulin signal peptide and the mutations associated with diabetes.…
Solution structures of insulin analogs.…
Solution structures of insulin analogs. A. Ensemble of NMR-derived structures DKP-insulin wild-type (WT).…
Two preproinsulin signal peptide mutations…
Two preproinsulin signal peptide mutations cause distinct cellular defects in beta cells. A.…
A proposed model of beta cell failure and diabetes caused by the defects…
Genetics is the study of how traits are encoded in DNA and passed from generation to generation.
The foundations for this scientific field were established by Gregor Mendel, a mid-nineteenth century monk whose experiments in breeding peas revealed the inheritance patterns of certain traits, such as pod colour or wrinkly seeds. Through these experiments, he was able to determine that some traits are dominant, and others recessive.
Today, we know that such traits are caused by different variants of the same gene, known as alleles. Genes are the regions of DNA that code for proteins, but their specific code can vary. Humans and various other – but not all – organisms have two copies of almost every gene, one from each of their biological parents.
These alleles can cause disease. For example, Huntington’s chorea is a dominant disorder, meaning people only need to inherit one copy of the Huntington’s allele to develop the condition. Cystic fibrosis, however, is a recessive disorder – a person must inherit two cystic fibrosis alleles to have the condition.
It took a while for Mendel’s work to gain the recognition it deserved. One proponent of his findings was the biologist William Bateson, who introduced the word “genetics” in 1905.
In the mid-twentieth century, biologists and mathematicians combined Mendel’s conclusions on inheritance with Charles Darwin’s theory of natural selection, in a movement known as the modern synthesis. This school of thought revolutionised our understanding of biology, transforming it from a discipline defined by observations and specimen collecting to a field underpinned by unifying principles and a mathematical framework.
In the decades that followed, the structure and function of DNA was determined, and we now understand how genes work, how they are passed down the generations, and how they mutate and evolve.
We now know that, in addition to single-gene traits like cystic fibrosis in people or wrinkly seeds in peas, a large number of traits are governed by multiple genes. One human example is height.
In addition to this, many traits are even more complex, being governed not only by many different genes that each have a tiny effect, but also being influenced by the environment that we live in. Intelligence and obesity are two examples of these.
To unpick the role of genes, geneticists use sophisticated statistical methods. Calculating the heritability of a trait, by tracking it in a population, gives an idea of the degree to which variation in that trait is attributable to genetics, rather than environmental conditions. Twin studies enable researchers to further determine the extent to which genes might be responsible for certain traits. Genome-wide association studies can be used to sift through data to pinpoint genes that seem to be associated with certain characteristics.
As our understanding of genetics has advanced, we’ve been able to develop new scientific techniques based on genes. Genetic modification involves inserting new genes into an organism, to give it additional traits or abilities, such as pesticide resistance. Gene therapy has been developed as a treatment for some single-gene disorders, and works by administering functional copies of particular genes to people who have faulty alleles.
Until recently, modifying the DNA of humans and other organisms has been a difficult and laborious task, but new gene editing techniques such as CRISPR mean that we can now change genes much more easily. If these techniques can be made safe enough for use in people, they could lead to significant new medical treatments, but also open the door to human enhancement – genetic changes designed not to treat disease, but to improve our appearance or abilities. Penny Sarchet
Our research focuses on understanding how genetic variation is generated and maintained in natural populations. By identifying genes contributing to adaptive phenotypic variation, we can use population and ecological genetics to gain insight into the evolutionary process.
For example, we use population genetics to:
(1) estimate the age of adaptive alleles
(2) to estimate the strength of selection using patterns of nucleotide variation
(3) predict the order in which alleles were selected
(4) determine if adaptive alleles were derived from standing genetic variation or new mutations.
We also use an ecological genetic approach by studying the spatial and temporal distribution of alleles. Thus, in addition to genetic crosses done in the laboratory, we study natural populations in the field. We have complementary projects focusing on:
(1) ecological genetics of clinal variation in pigmentation and skeletal morphology using museum skins collected in the 1920's
(2) population genetics and phylogeography of Peromyscus polionotus populations in the southwestern U.S.
(3) conservation genetics of endangered beach mouse subspecies.
Our lab takes advantage of phenotypic variation in natural populations of Peromyscus. Our lab has several field sites including in Florida, Nebraska, Bulgaria, South Carolina and New Mexico. We have recently begun collaborative work with researchers in Brazil. By examining populations occupying similar environments in diverse locales, we can ask if similar or different genetic mechanisms underlie convergent phenotypes.
Natural history collections
We are part of the Museum of Comparative Zoology (MCZ) at Harvard University. Our collections are accessioned in the Mammal Department and are available to researchers throughout the world. The MCZ Mammal Collection is one of the largest historic, geographic, and taxonomically diverse university systematic collections in the world.
Natural history museums are repositories of morphological and distributional information. Museum specimens of Peromyscus polionotus date back to the late 1800's, but the most extensive collections belong to Francis Sumner from his surveys of Peromyscus populations in the 1920's. His classic studies on intraspecific variation laid the groundwork for our own research.
Museum specimens provide us with phenotypic data from known locations. In addition, we are able to extract DNA from these specimens using ancient DNA techniques. Thus, we can take advantage of hundreds of specimens from extant species as well as species that have gone extinct in historical time. These collections also allow us to incorporate a temporal component to our research, enabling us to document changes in both genetic and phenotypic variation over time.
Gene mutation: a change to the base sequence of a gene.
Sickle cell anaemia is a genetic disease that affects red blood cells in the body. It is due to a mutation on the Hb gene which codes for a polypeptide of 146 amino acids which is part of haemoglobin (haemoglobin is an important protein component in red blood cells). In sickle cell anaemia the codon GAG found in the normal Hb gene is mutated to GTG. This is called a base substitution mutation as adenine (A) is replaced by thymine (T). This means that when the mutated gene is transcribed, a codon in the messenger RNA will be different. Instead of the normal codon GAG, the messenger RNA will contain the codon GUG. This in turn will result in a mistake during translation. In a healthy individual the codon GAG on the messenger RNA matches with the anticodon CUC on the transfer RNA carrying the amino acid glutamic acid. However, if the mutated gene is present then GUG on the messenger RNA matches with the anticodon CAC on the transfer RNA which carries the amino acid valine. So the base substitution mutation has caused glutamic acid to be replaced by valine on the sixth position on the polypeptide. This results in haemoglobin S being present in red blood cells instead of the normal haemoglobin A. This has an effect on the phenotype as instead of normal donut shaped red blood cells being produced some of the red blood cells will be sickle shaped. As a result these sickle shaped red blood cells cannot carry oxygen as efficiently as normal red blood cells would. However, there is an advantage to sickle cell anemia. The sickle cell red blood cells give resistance to malaria and so the allele Hb s on the Hb gene which causes sickle cell anemia is quite common in parts of the world where malaria is found as it provides an advantage over the disease.
Genetics: The Study of Heredity
Genetics is the study of how heritable traits are transmitted from parents to offspring. Humans have long observed that traits tend to be similar in families. It wasn’t until the mid-nineteenth century that larger implications of genetic inheritance began to be studied scientifically.
In 1858, Charles Darwin and Alfred Russell Wallace jointly announced their theory of natural selection. According to Darwin’s observations, in nearly all populations individuals tend to produce far more offspring than are needed to replace the parents. If every individual born were to live and reproduce still more offspring, the population would collapse. Overpopulation leads to competition for resources.
Darwin observed that it is very rare for any two individuals to be exactly alike. He reasoned that these natural variations among individuals lead to natural selection. Individuals born with variations that confer an advantage in obtaining resources or mates have greater chances of reproducing offspring who would inherit the favorable variations. Individuals with different variations might be less likely to reproduce.
Darwin was convinced that natural selection explained how natural variations could lead to new traits in a population, or even new species. While he had observed the variations existent in every population, he was unable to explain how those variations came about. Darwin was unaware of the work being done by a quiet monk named Gregor Mendel.
Inheritance of traits
In 1866, Gregor Mendel published the results of years of experimentation in breeding pea plants. He showed that both parents must pass discrete physical factors which transmit information about their traits to their offspring at conception. An individual inherits one such unit for a trait from each parent. Mendel's principle of dominance explained that most traits are not a blend of the father’s traits and those of the mother as was commonly thought. Instead, when an offspring inherits a factor for opposing forms of the same trait, the dominant form of that trait will be apparent in that individual. The factor for the recessive trait, while not apparent, is still part of the individual’s genetic makeup and may be passed to offspring.
Mendel’s experiments demonstrated that when sex cells are formed, the factors for each trait that an individual inherits from its parents are separated into different sex cells. When the sex cells unite at conception the resulting offspring will have at least two factors (alleles) for each trait. One inherited factor from the mother and one from the father. Mendel used the laws of probability to demonstrate that when the sex cells are formed, it is a matter of chance as to which factor for a given trait is incorporated into a particular sperm or egg.
We now know that simple dominance does not explain all traits. In cases of co-dominance, both forms of the trait are equally expressed. Incomplete dominance results in a blending of traits. In cases of multiple alleles, there are more than just two possible ways a given gene can be expressed. We also now know that most expressed traits, such as the many variations in human skin color, are influenced by many genes all acting on the same apparent trait. In addition, each gene that acts on the trait may have multiple alleles. Environmental factors can also interact with genetic information to supply even more variation. Thus sexual reproduction is the biggest contributor to genetic variation among individuals of a species.
Twentieth-century scientists came to understand that combining the ideas of genetics and natural selection could lead to enormous strides in understanding the variety of organisms that inhabit our earth.
Scientists realized that the molecular makeup of genes must include a way for genetic information to be copied efficiently. Each cell of a living organism requires instructions on how and when to build the proteins that are the basic building blocks of body structures and the &ldquoworkhorses&rdquo responsible for every chemical reaction necessary for life. In 1958, when James Watson and Francis Crick described the structure of the DNA molecule, this chemical structure explained how cells use the information from the DNA stored in the cell’s nucleus to build proteins. Each time cells divide to form new cells, this vast chemical library must be copied so that the daughter cells have the information required to function. Inevitably, each time the DNA is copied, there are minute changes. Most such changes are caught and repaired immediately. However, if the alteration is not repaired the change may result in an altered protein. Altered proteins may not function normally. Genetic disorders are conditions that result when malfunctioning proteins adversely affect the organism. [Gallery: Images of DNA Structures]
In very rare cases the altered protein may function better than the original or result in a trait that confers a survival advantage. Such beneficial mutations are one source of genetic variation.
Another source of genetic variation is gene flow, the introduction of new alleles to a population. Commonly, this is due to simple migration. New individuals of the same species enter a population. Environmental conditions in their previous home may have favored different forms of traits, for example, lighter colored fur. Alleles for these traits would be different from the alleles present in the host population. When the newcomers interbreed with the host population, they introduce new forms of the genes responsible for traits. Favorable alleles may spread through the population. [Countdown: Genetics by the Numbers &mdash 10 Tantalizing Tales]
Genetic drift is a change in allele frequency that is random rather than being driven by selection pressures. Remember from Mendel that alleles are sorted randomly into sex cells. It could just happen that both parents contribute the same allele for a given trait to all of their offspring. When the offspring reproduce they can only transmit the one form of the trait that they inherited from their parents. Genetic drift can cause large changes in a population in only a few generations especially if the population is very small. Genetic drift tends to reduce genetic variation in a population. In a population without genetic diversity there is a greater chance that environmental change may decimate the population or drive it to extinction.
Rare Genetic Mutation Links Two Neurological Diseases
A man with ALS uses a head-mounted laser pointer to communicate with his wife by pointing to letters and words on a communication board. In 2011, an IRP-led study identified a genetic mutation responsible for many cases of ALS and frontotemporal dementia. Image credit: Fezcat via Wikimedia Commons
June was an important month in the life of baseball great Lou Gehrig. It was the month he was born and the month he was first picked for the Yankees’ starting lineup. Sadly, it was also the month in 1939 when he was diagnosed with the neurological disease that bears his name — Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS) — and the month he died of that disease two years later. It is appropriate then that ALS Awareness Day is observed on June 21 as a day of hope for those searching for effective treatments and, ultimately, a cure.
IRP senior investigator Bryan J. Traynor, M.D., Ph.D., a neurologist at the National Institute on Aging (NIA), is one of the people leading that search. Best known for his work unraveling the genetic causes of ALS and frontotemporal dementia (FTD), he led an international consortium of researchers that uncovered a mutation on chromosome 9 that is the most common ‘familial’ cause of both ALS and FTD. In fact, this mutation, which disrupts the function of the C90RF72 gene, is responsible for 40 percent of all familial cases of ALS and FTD in European and North American populations, meaning cases in which a family member also has the disease. The discovery, published in 2011, revolutionized the scientific understanding of neurodegenerative diseases and the relationships between them. It also suggested a potential target for future gene therapies.
“The most common gene prior to this finding accounted for about 12 percent of familial cases and here was a gene that explained nearly half of all the familial cases,” Dr. Traynor says. “I think seeing that number was really the moment when it dawned on me just how big of a finding this was.”
American baseball player Lou Gehrig was diagnosed with ALS on his 36th birthday. The disease subsequently became commonly known as Lou Gehrig’s disease.
ALS is a devastating neurodegenerative disease that results from the death of nerve cells in the brain and spinal cord. This causes muscles to shrink and weaken, leading to difficulty moving, swallowing, and, eventually, breathing. It exists in two forms. ‘Sporadic’ ALS is the most common form, affecting about 90 to 95 percent of all patients, and occurs when someone has the bad luck of being born with a random, disease-causing mutation. Familial ALS, which affects the remaining 5 to 10 percent of patients, occurs when a mutation is passed down through generations.
Previous studies had shown that families with a history of ALS also had a history of FTD, which occurs when nerve cells in the frontal and temporal lobes of the brain are lost, causing changes in behavior and personality. In addition, genetic mapping had linked both conditions to the same stretch of DNA on chromosome 9, which was made up of about 7 million base pairs.
“We were just beginning to get an inkling that those two diseases were related to each other,” Dr. Traynor says. “It was pretty rare, but nonetheless, it was proof-of-concept that you could actually have a gene that caused both FTD and ALS.”
In 2009, Dr. Traynor’s NIH team began a genetic study of ALS in Finland, a country with below-average genetic diversity for historical reasons and an unusually high incidence of ALS. After testing samples from about 300 Finnish ALS and FTD patients and 300 people with neither condition, the IRP scientists noticed a common genetic haplotype that exists in the Finnish population. A haplotype is a set of genetic information that is inherited together as a set from a single parent, rather than having a mix of DNA from both parents. It turned out that the vast majority of ALS and FTD patients across Europe and North America had this Finnish haplotype, which included specific variations of three genes: MOBKL2b, IFNK, and C9ORF72.
ALS destroys motor neurons like this one that connect to muscle fibers. Without them, movement and vital functions like swallowing and breathing become difficult.
“One of the things about genetics is you can use it as a kind of time machine,” Dr. Traynor says. “What this finding indicates to us is there was probably a one-off genetic event that occurred about 1500 years ago, around the time of the fall of the Roman Empire. We think it was actually the Vikings on their summer holidays who spread this version of the C9ORF72 gene around the rest of Europe.”
Still, even though they had identified the genetic site where a disease-causing mutation must exist and a common set of variations in the genetic profile, researchers had yet to identify the specific gene that was causing all the problems. With a relatively rare disease like ALS, even after narrowing the search to a particular location on a single chromosome, finding a mutation among 7 million base pairs is difficult.
Other research groups all around the world were searching, unsuccessfully, for the mutation, but NIH’s collaborative infrastructure and resources gave Dr. Traynor’s team a competitive edge. They reached out to these other scientists and invited them to send their DNA samples to him for sequencing. He ultimately shared the resulting data for everyone to analyze at the same time, and eventually the globe-spanning team of scientists narrowed the area down to about 200,000 base pairs — “a blink of the eye in genetic terms,” according to Dr. Traynor.
In 2011, Dr. Traynor began searching the DNA samples his team had gathered for variations that didn’t show up in unaffected individuals. This narrowed it down to eight suspects.
“I noticed that six of these eight variations were all very close together — within 30 base pairs — which they shouldn’t have been,” Dr. Traynor recalls. “They should have been distributed randomly across the 200,000 base pairs we were looking at.”
He compared the samples to a normal ‘reference’ genome and saw that the C9ORF72 gene located in this genetic segment contained multiple repeats of a specific set of base pairs in the patient samples. The reference genome had three repetitions of this genetic sequence within the C9ORF72 gene, but in the DNA from ALS and FTD patients, there were many more. The genetic information was repeated like a bit of song on a skipping record.
“I remember sitting in front of the computer looking at this and that’s when the penny dropped,” Dr. Traynor says. “It was an expansion of six base pairs that were being repeated again and again and again.”
Of course, Dr. Traynor wasn’t the only one hot on the trail of this mutation. The scientific paper announcing his lab’s discovery was published in the journal Neuron alongside a study, led by Mayo Clinic neurogeneticist Rosa Rademakers, Ph.D., that independently linked the same mutation to ALS and FTD, leaving little doubt that the connection was real.
"We’re now beginning to see a grand unified theory of everything coming together from the genomics,” says Dr. Traynor.
IRP senior investigator Bryan Traynor
Since then, Dr. Traynor has continued to make important discoveries about the genetic causes of ALS. For instance, he and his collaborator John Landers at the University of Massachusetts Medical School have identified another gene, called KIF5A, which appears to be involved in damage to the cytoskeleton that provides structure to long neural cells. This type of damage appears to be a significant feature of ALS.
As a practicing neurologist, Dr. Traynor is now focusing his efforts on directing this genetic understanding toward identifying therapies for ALS and FTD. While fixing the C9ORF72, KIF5A, or other mutations through gene editing or CRISPR may be possible one day, Dr. Traynor believes that manipulating the responsible genes’ activity is the most likely direction for therapy right now. He’s excited that such a breakthrough could come in just a few years.
“It's what gets me out of the bed in the morning: just trying to get this done,” Dr. Traynor says. “It's why we're doing what we're doing, why we work at the NIH. We're here to pursue the big ideas.”
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The molecular biology of galactosemia
Classic galactosemia is an autosomal recessive disorder caused by the deficiency of galactose 1-phosphate uridyltransferase (GALT). Although the potentially lethal, neonatal hepatotoxic syndrome is prevented by new-born screening and galactose restriction, long-term outcome for older patients with galactosemia remains problematic. After the cloning and sequencing of the GALT gene, more than 130 mutations in the GALT gene have been associated with GALT deficiency this review relates them to function and clinical outcome. Two common mutations, Q188R and K285N, account for more than 70% of G alleles in the white population and are associated with classic galactosemia and impaired GALT function. In the black population, S135L accounts for 62% of the alleles causing galactosemia and is associated with good outcomes. A large 5 kb deletion in the GALT gene is found in Ashkenazim Jews. The Duarte galactosemia variant is caused by N314D. Homozygosity for N314D reduces GALT activity to 50%. When either E203K or a 1721C→T transition (Los Angeles variant) are present in cis with N314D, GALT activity reverts to normal. In this review, we discuss the structural biology of these mutations as they affect both the GALT enzyme and patient outcome.
Genetic mutations and new alleles - Biology
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In addition to natural selection, allelic frequencies in a population can change over time by mutations, gene flow, and genetic drift.
Genetic variation can be generated in a population, for instance, these beetles, simply by random mutations. Harmful mutations in the DNA of organisms are quickly eliminated from the population by natural selection, while beneficial ones spread.
Additionally, genes from outside the population can contribute to the genetic variation through the immigration of new individuals. When beetles from two populations regularly exchange individuals, the two gene pools will eventually become more similar.
Last, if the population size decreases due to some random event, such as a storm, the allelic frequencies will likely change dramatically, simply due to the smaller number of remaining alleles in the population. This change is referred to as genetic drift.
32.3: Mutation, Gene Flow, and Genetic Drift
In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
Mechanisms of Genetic Variation
The original sources of genetic variation are mutations, which are changes in the nucleotide sequence of DNA. Mutations create new alleles and increase genetic variability. Most mutations do not cause significant changes to the health or functioning of an organism. However, if a mutation reduces the chances of survival, the organism may die before reproducing. Therefore, such harmful mutations are likely to be eliminated by natural selection.
Individuals in natural populations may also select their mates based on certain characteristics, and thus do not reproduce randomly. In this case, alleles for the traits that are selected against will become less frequent in the population.
Furthermore, populations can experience gene flow, the transfer of alleles into and out of gene pools, due to migration. A classic example of gene flow is observed in most baboon species. Female baboons mate most frequently with dominant males in a troop. Juvenile male baboons almost always leave their birth troops, likely to avoid inbreeding, and join a new troop, where they may pass their genes to offspring.
In genetic drift, chance events alter the allele frequencies of a population. A major disturbance, such as a natural disaster, may drastically reduce population size and thereby diminish genetic variation. The resulting composition of the gene pool was selected randomly (i.e., surviving the disturbance was not determined by the genetic make-up of the individual). Such a reduction of genetic diversity is called a genetic bottleneck.
Sometimes, a population may become fragmented into smaller populations due to urban development or other events. A new population is started by a small group of members of the original population and by chance, a previously rare allele may be relatively frequent. This effect on gene frequencies is known as the founder effect.
Importance of Genetic Variability
Genetic variation is the basis for evolution. Natural selection can occur only if multiple forms of genes (alleles) are present in the population&mdashfavoring alleles that confer a fitness advantage under current conditions. On the other hand, loss of genetic variation can have detrimental effects on populations. If the gene pool does not contain gene variants that promote survival and reproduction when the environment changes, the population cannot adapt and may vanish. These negative effects are more pronounced in smaller populations, as the gene pool is smaller to begin with. Smaller populations are hence more vulnerable to stochastic events. Conservation efforts often focus on increasing genetic variability via selective breeding of individuals in small and endangered populations.
Serieys, Laurel E. K., Amanda Lea, John P. Pollinger, Seth P. D. Riley, and Robert K. Wayne. &ldquoDisease and Freeways Drive Genetic Change in Urban Bobcat Populations.&rdquo Evolutionary Applications 8, no. 1 (2015): 75&ndash92. [Source]
Miller, Webb, Vanessa M. Hayes, Aakrosh Ratan, Desiree C. Petersen, Nicola E. Wittekindt, Jason Miller, Brian Walenz, et al. &ldquoGenetic Diversity and Population Structure of the Endangered Marsupial Sarcophilus harrisii (Tasmanian Devil).&rdquo Proceedings of the National Academy of Sciences 108, no. 30 (July 26, 2011): 12348&ndash53. [Source]