Genetic hitchhiking

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Genetic hitchhiking, also called genetic draft or the hitchhiking effect, [1] is when an allele changes frequency not because it itself is under natural selection, but because it is near another gene that is undergoing a selective sweep and that is on the same DNA chain. When one gene goes through a selective sweep, any other nearby polymorphisms that are in linkage disequilibrium will tend to change their allele frequencies too. [2] Selective sweeps happen when newly appeared (and hence still rare) mutations are advantageous and increase in frequency. Neutral or even slightly deleterious alleles that happen to be close by on the chromosome 'hitchhike' along with the sweep. In contrast, effects on a neutral locus due to linkage disequilibrium with newly appeared deleterious mutations are called background selection. Both genetic hitchhiking and background selection are stochastic (random) evolutionary forces, like genetic drift. [3]

Contents

History

The term hitchhiking was coined in 1974 by Maynard Smith and John Haigh. [1] Subsequently the phenomenon was studied by John H. Gillespie and others. [4]

Outcomes

Hitchhiking occurs when a polymorphism is in linkage disequilibrium with a second locus that is undergoing a selective sweep. The allele that is linked to the adaptation will increase in frequency, in some cases until it becomes fixed in the population. The other allele, which is linked to the non-advantageous version, will decrease in frequency, in some cases until extinction. [5] [6] Overall, hitchhiking reduces the amount of genetic variation. A hitchhiker mutation (or passenger mutation in cancer biology) may itself be neutral, advantageous, or deleterious. [7]

Recombination can interrupt the process of genetic hitchhiking, ending it before the hitchhiking neutral or deleterious allele becomes fixed or goes extinct. [6] The closer a hitchhiking polymorphism is to the gene under selection, the less opportunity there is for recombination to occur. This leads to a reduction in genetic variation near a selective sweep that is closer to the selected site. [8] This pattern is useful for using population data to detect selective sweeps, and hence to detect which genes have been under very recent selection.

Draft versus drift

Both genetic drift and genetic draft are random evolutionary processes, i.e. they act stochastically and in a way that is not correlated with selection at the gene in question. Drift is the change in the frequency of an allele in a population due to random sampling in each generation. [9] Draft is the change in the frequency of an allele due to the randomness of what other non-neutral alleles it happens to be found in association with.

Assuming genetic drift is the only evolutionary force acting on an allele, after one generation in many replicated idealised populations each of size N, each starting with allele frequencies of p and q, the newly added variance in allele frequency across those populations (i.e. the degree of randomness of the outcome) is . [3] This equation shows that the effect of genetic drift is heavily dependent on population size, defined as the actual number of individuals in an idealised population. Genetic draft results in similar behavior to the equation above, but with an effective population size that may have no relationship to the actual number of individuals in the population. [3] Instead, the effective population size may depend on factors such as the recombination rate and the frequency and strength of beneficial mutations. The increase in variance between replicate populations due to drift is independent, whereas with draft it is autocorrelated, i.e. if an allele frequency goes up because of genetic drift, that contains no information about the next generation, whereas if it goes up because of genetic draft, it is more likely to go up than down in the next generation. [9] Genetic draft generates a different allele frequency spectrum to genetic drift. [10]

Applications

Sex chromosomes

The Y chromosome does not undergo recombination, making it particularly prone to the fixation of deleterious mutations via hitchhiking. This has been proposed as an explanation as to why there are so few functional genes on the Y chromosome. [11]

Mutator evolution

Hitchhiking is necessary for the evolution of higher mutation rates to be favored by natural selection on evolvability. A hypothetical mutator M increases the general mutation rate in the area around it. Due to the increased mutation rate, the nearby A allele may be mutated into a new, advantageous allele, A*

--M------A-- -> --M------A*--

The individual in which this chromosome lies will now have a selective advantage over other individuals of this species, so the allele A* will spread through the population by the normal processes of natural selection. M, due to its proximity to A*, will be dragged through into the general population. This process only works when M is very close to the allele it has mutated. A greater distance would increase the chance of recombination separating M from A*, leaving M alone with any deleterious mutations it may have caused. For this reason, evolution of mutators is generally expected to happen largely in asexual species where recombination cannot disrupt linkage disequilibrium. [12]

Neutral theory of molecular evolution

The neutral theory of molecular evolution assumes that most new mutations are either deleterious (and quickly purged by selection) or else neutral, with very few being adaptive. It also assumes that the behavior of neutral allele frequencies can be described by the mathematics of genetic drift. Genetic hitchhiking has therefore been viewed as a major challenge to neutral theory, and an explanation for why genome-wide versions of the McDonald–Kreitman test appear to indicate a high proportion of mutations becoming fixed for reasons connected to selection. [13]

Related Research Articles

<span class="mw-page-title-main">Mutation</span> Alteration in the nucleotide sequence of a genome

In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements.

<span class="mw-page-title-main">Genetic drift</span> Concept in genetics

Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance.

<span class="mw-page-title-main">Molecular evolution</span> Process of change in the sequence composition of cellular molecules across generations

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, the evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

<span class="mw-page-title-main">Neutral theory of molecular evolution</span>

The neutral theory of molecular evolution holds that most evolutionary changes occur at the molecular level, and most of the variation within and between species are due to random genetic drift of mutant alleles that are selectively neutral. The theory applies only for evolution at the molecular level, and is compatible with phenotypic evolution being shaped by natural selection as postulated by Charles Darwin. The neutral theory allows for the possibility that most mutations are deleterious, but holds that because these are rapidly removed by natural selection, they do not make significant contributions to variation within and between species at the molecular level. A neutral mutation is one that does not affect an organism's ability to survive and reproduce. The neutral theory assumes that most mutations that are not deleterious are neutral rather than beneficial. Because only a fraction of gametes are sampled in each generation of a species, the neutral theory suggests that a mutant allele can arise within a population and reach fixation by chance, rather than by selective advantage.

<span class="mw-page-title-main">Population genetics</span> Subfield of genetics

Population genetics is a subfield of genetics that deals with genetic differences within and among populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and population structure.

Allele frequency, or gene frequency, is the relative frequency of an allele at a particular locus in a population, expressed as a fraction or percentage. Specifically, it is the fraction of all chromosomes in the population that carry that allele over the total population or sample size. Microevolution is the change in allele frequencies that occurs over time within a population.

Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. In other words, the nearer two genes are on a chromosome, the lower the chance of recombination between them, and the more likely they are to be inherited together. Markers on different chromosomes are perfectly unlinked, although the penetrance of potentially deleterious alleles may be influenced by the presence of other alleles, and these other alleles may be located on other chromosomes than that on which a particular potentially deleterious allele is located.

<span class="mw-page-title-main">Chromosomal inversion</span> Chromosome rearrangement in which a segment of a chromosome is reversed

An inversion is a chromosome rearrangement in which a segment of a chromosome becomes inverted within its original position. An inversion occurs when a chromosome undergoes a two breaks within the chromosomal arm, and the segment between the two breaks inserts itself in the opposite direction in the same chromosome arm. The breakpoints of inversions often happen in regions of repetitive nucleotides, and the regions may be reused in other inversions. Chromosomal segments in inversions can be as small as 100 kilobases or as large as 100 megabases. The number of genes captured by an inversion can range from a handful of genes to hundreds of genes. Inversions can happen either through ectopic recombination, chromosomal breakage and repair, or non-homologous end joining.

Genetic load is the difference between the fitness of an average genotype in a population and the fitness of some reference genotype, which may be either the best present in a population, or may be the theoretically optimal genotype. The average individual taken from a population with a low genetic load will generally, when grown in the same conditions, have more surviving offspring than the average individual from a population with a high genetic load. Genetic load can also be seen as reduced fitness at the population level compared to what the population would have if all individuals had the reference high-fitness genotype. High genetic load may put a population in danger of extinction.

Coalescent theory is a model of how alleles sampled from a population may have originated from a common ancestor. In the simplest case, coalescent theory assumes no recombination, no natural selection, and no gene flow or population structure, meaning that each variant is equally likely to have been passed from one generation to the next. The model looks backward in time, merging alleles into a single ancestral copy according to a random process in coalescence events. Under this model, the expected time between successive coalescence events increases almost exponentially back in time. Variance in the model comes from both the random passing of alleles from one generation to the next, and the random occurrence of mutations in these alleles.

<i>The Neutral Theory of Molecular Evolution</i>

The Neutral Theory of Molecular Evolution is an influential monograph written in 1983 by Japanese evolutionary biologist Motoo Kimura. While the neutral theory of molecular evolution existed since his article in 1968, Kimura felt the need to write a monograph with up-to-date information and evidences showing the importance of his theory in evolution.

In genetics, a selective sweep is the process through which a new beneficial mutation that increases its frequency and becomes fixed in the population leads to the reduction or elimination of genetic variation among nucleotide sequences that are near the mutation. In selective sweep, positive selection causes the new mutation to reach fixation so quickly that linked alleles can "hitchhike" and also become fixed.

<span class="mw-page-title-main">Masatoshi Nei</span> Japanese-American geneticist (1931–2023)

Masatoshi Nei was a Japanese-born American evolutionary biologist who was affiliated with the Department of Biology at Temple University as an adjunct Laura H. Carnell Professor. He was previously an Evan Pugh Professor of Biology at Pennsylvania State University and Director of the Institute of Molecular Evolutionary Genetics; working there from 1990 to 2015.

Background selection describes the loss of genetic diversity at a non-deleterious locus due to negative selection against linked deleterious alleles. It is one form of linked selection, where the maintenance or removal of an allele from a population is dependent upon the alleles in its linkage group. The name emphasizes the fact that the genetic background, or genomic environment, of a neutral mutation has a significant impact on whether it will be preserved or purged from a population. In some cases, the term background selection is used broadly to refer to all forms of linked selection, but most often it is used only when neutral variation is reduced due to negative selection against deleterious mutations. Background selection and all forms of linked selection contradict the assumption of the neutral theory of molecular evolution that the fixation or loss of neutral alleles is entirely stochastic, the result of genetic drift. Instead, these models predict that neutral variation is correlated with the selective pressures acting on linked non-neutral genes, that neutral traits are not necessarily oblivious to selection. Because they segregate together, non-neutral mutations linked to neutral polymorphisms result in decreased levels of genetic variation relative to predictions of neutral evolution.

In natural selection, negative selection or purifying selection is the selective removal of alleles that are deleterious. This can result in stabilising selection through the purging of deleterious genetic polymorphisms that arise through random mutations.

In population genetics, the Hill–Robertson effect, or Hill–Robertson interference, is a phenomenon first identified by Bill Hill and Alan Robertson in 1966. It provides an explanation as to why there may be an evolutionary advantage to genetic recombination.

In population genetics, fixation is the change in a gene pool from a situation where there exists at least two variants of a particular gene (allele) in a given population to a situation where only one of the alleles remains. That is, the allele becomes fixed. In the absence of mutation or heterozygote advantage, any allele must eventually be lost completely from the population or fixed. Whether a gene will ultimately be lost or fixed is dependent on selection coefficients and chance fluctuations in allelic proportions. Fixation can refer to a gene in general or particular nucleotide position in the DNA chain (locus).

Fay and Wu's H is a statistical test created by and named after two researchers Justin Fay and Chung-I Wu. The purpose of the test is to distinguish between a DNA sequence evolving randomly ("neutrally") and one evolving under positive selection. This test is an advancement over Tajima's D, which is used to differentiate neutrally evolving sequences from those evolving non-randomly. Fay and Wu's H is frequently used to identify sequences which have experienced selective sweeps in their evolutionary history.

Allele age is the amount of time elapsed since an allele first appeared due to mutation. Estimating the time at which a certain allele appeared allows researchers to infer patterns of human migration, disease, and natural selection. Allele age can be estimated based on (1) the frequency of the allele in a population and (2) the genetic variation that occurs within different copies of the allele, also known as intra-allelic variation. While either of these methods can be used to estimate allele age, the use of both increases the accuracy of the estimation and can sometimes offer additional information regarding the presence of selection.

In genetics, when multiple copies of a beneficial mutation become established and fix together it is called soft sweep. Depending on the origin of these copies, linked variants might then be retained and emerge as haplotype structures in the population. There are two major forms of soft sweeps:

References

  1. 1 2 Smith, J. M.; Haigh, J. (1974). "The hitch-hiking effect of a favourable gene". Genetical Research. 23 (1): 23–35. doi: 10.1017/S0016672300014634 . PMID   4407212.
  2. ↑ Futuyma, Douglas J. 2013. Evolution: Third Edition. Sinauer Associates, Inc: Sunderland, MA.
  3. 1 2 3 Gillespie, John H (2001). "Is the population size of a species relevant to its evolution?". Evolution. 55 (11): 2161–2169. doi: 10.1111/j.0014-3820.2001.tb00732.x . PMID   11794777.
  4. ↑ Gillespie, John H. (2000). "Genetic Drift in an Infinite Population: The Pseudohitchhiking Model". Genetics. 155 (2): 909–919. doi:10.1093/genetics/155.2.909. PMC   1461093 . PMID   10835409.
  5. ↑ Kreitman, Marty (2001). "Hitchhiking Effect". Encyclopedia of Genetics. pp. 952–953. doi:10.1006/rwgn.2001.0619. ISBN   9780122270802.
  6. 1 2 Fay, Justin C.; Wu, Chung-I. (2000). "Hitchhiking Under Positive Darwinian Selection". Genetics. 155 (3): 1405–1413. doi:10.1093/genetics/155.3.1405. PMC   1461156 . PMID   10880498.
  7. ↑ Good, B. H.; Desai, M. M. (5 September 2014). "Deleterious Passengers in Adapting Populations". Genetics. 198 (3): 1183–1208. doi:10.1534/genetics.114.170233. PMC   4224160 . PMID   25194161.
  8. ↑ Braverman, John M.; Hudson, Richard R.; Kaplan, Norman L.; Langley, Charles H.; Barton, Wolfgang (1995). "The Hitchhiking Effect on the Site Frequency Spectrum of DNA Polymorphisms". Genetics. 140 (2): 783–797. doi:10.1093/genetics/140.2.783. PMC   1206652 . PMID   7498754.
  9. 1 2 Masel, J (2011). "Genetic drift". Current Biology. 21 (20): 837–838. doi: 10.1016/j.cub.2011.08.007 . PMID   22032182.
  10. ↑ Neher, R. A.; Shraiman, B. I. (30 May 2011). "Genetic Draft and Quasi-Neutrality in Large Facultatively Sexual Populations". Genetics. 188 (4): 975–996. doi:10.1534/genetics.111.128876. PMC   3176096 . PMID   21625002.
  11. ↑ Rice, WR (1987). "Genetic hitchhiking and the evolution of reduced genetic activity of the Y sex chromosome". Genetics. 116 (1): 161–167. doi:10.1093/genetics/116.1.161. PMC   1203114 . PMID   3596229.
  12. ↑ Andre, J.-B. (11 October 2005). "The Evolution of Mutation Rate in Finite Asexual Populations". Genetics. 172 (1): 611–626. doi:10.1534/genetics.105.046680. PMC   1456187 . PMID   16157667.
  13. ↑ Hahn, Matthew W. (February 2008). "Toward a selection theory of molecular evolution". Evolution. 62 (2): 255–265. doi: 10.1111/j.1558-5646.2007.00308.x . PMID   18302709.
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