View source for Population genetics

{{Short description|Subfield of genetics}}
{{Evolutionary biology}}
{{genetic genealogy}}
'''Population genetics''' is a subfield of [[genetics]] that deals with genetic differences within and among [[population]]s, and is a part of [[evolutionary biology]]. Studies in this branch of [[biology]] examine such phenomena as [[Adaptation (biology)|adaptation]], [[speciation]], and [[population stratification|population structure]].<ref>{{Cite web |url=https://www.nature.com/subjects/population-genetics |title=Population genetics - Latest research and news |website=www.nature.com |access-date=2018-01-29}}</ref>

Population genetics was a vital ingredient in the [[emergence]] of the [[Modern synthesis (20th century)|modern evolutionary synthesis]]. Its primary founders were [[Sewall Wright]], [[J. B. S. Haldane]] and [[Ronald Fisher]], who also laid the foundations for the related discipline of [[quantitative genetics]]. Traditionally a highly mathematical discipline, modern population genetics encompasses theoretical, laboratory, and field work. Population genetic models are used both for [[statistical inference]] from DNA sequence data and for proof/disproof of concept.<ref>{{cite journal |last1=Servedio |first1=Maria R. |author-link1=Maria Servedio |last2=Brandvain |first2=Yaniv |last3=Dhole |first3=Sumit |last4=Fitzpatrick |first4=Courtney L. |last5=Goldberg |first5=Emma E. |last6=Stern |first6=Caitlin A. |last7=Van Cleve |first7=Jeremy |last8=Yeh |first8=D. Justin |title=Not Just a Theory—The Utility of Mathematical Models in Evolutionary Biology |journal=PLOS Biology |date=9 December 2014 |volume=12 |issue=12 |pages=e1002017 |doi=10.1371/journal.pbio.1002017 |pmid=25489940 |pmc=4260780 |doi-access=free }}</ref>

What sets population genetics apart from newer, more phenotypic approaches to modelling evolution, such as [[evolutionary game theory]] and [[evolutionary invasion analysis|adaptive dynamics]], is its emphasis on such genetic phenomena as [[dominance (genetics)|dominance]], [[epistasis]], the degree to which [[genetic recombination]] breaks [[linkage disequilibrium]], and the random phenomena of [[mutation]] and [[genetic drift]]. This makes it appropriate for comparison to [[population genomics]] data.

==History==

Population genetics began as a reconciliation of [[Mendelian inheritance]] and [[biostatistics]] models. [[Natural selection]] will only cause evolution if there is enough [[genetic variation]] in a population. Before the discovery of [[Mendelian genetics]], one common hypothesis was [[blending inheritance]]. But with blending inheritance, genetic variance would be rapidly lost, making evolution by natural or sexual selection implausible. The [[Hardy–Weinberg principle]] provides the solution to how variation is maintained in a population with Mendelian inheritance. According to this principle, the frequencies of alleles (variations in a gene) will remain constant in the absence of selection, mutation, migration and genetic drift.<ref name="Ewens W.J. 2004">{{cite book |last=Ewens |first=W.J. |year=2004 |title=Mathematical Population Genetics |publisher=Springer |location=New York |isbn=978-0-387-20191-7 |edition=2nd }}</ref>

{{Multiple image |direction=vertical |align=right |image1=Biston.betularia.7200.jpg |image2=Biston.betularia.f.carbonaria.7209.jpg |width=200 |caption1=The typical white-bodied form of the [[peppered moth]] |caption2=[[Industrial melanism]]: the black-bodied form of the peppered moth appeared in polluted areas.}}

The next key step was the work of the British biologist and statistician [[Ronald Fisher]]. In a series of papers starting in 1918 and culminating in his 1930 book ''[[The Genetical Theory of Natural Selection]]'', Fisher showed that the continuous variation measured by the biometricians could be produced by the combined action of many discrete genes, and that natural selection could change allele frequencies in a population, resulting in evolution. In a series of papers beginning in 1924, another British geneticist, [[J. B. S. Haldane]], worked out the mathematics of allele frequency change at a single gene [[Locus (genetics)|locus]] under a broad range of conditions. Haldane also applied statistical analysis to real-world examples of natural selection, such as [[peppered moth evolution]] and [[industrial melanism]], and showed that [[selection coefficient]]s could be larger than Fisher assumed, leading to more rapid adaptive evolution as a camouflage strategy following increased pollution.<ref name="Bowler325-339">{{cite book |last=Bowler |first=Peter J. |author-link=Peter J. Bowler |title=Evolution : the history of an idea |year=2003 |publisher=University of California Press |location=Berkeley |isbn=978-0-520-23693-6 |edition=3rd |pages=[https://archive.org/details/evolutionhistory0000bowl_n7y8/page/325 325–339] |url=https://archive.org/details/evolutionhistory0000bowl_n7y8/page/325 }}</ref><ref name="Larson221-243">{{cite book |last=Larson |first=Edward J. |title=Evolution : the remarkable history of a scientific theory |year=2004 |publisher=Modern Library |location=New York |isbn=978-0-679-64288-6 |edition=Modern Library |pages=[https://archive.org/details/evolutionremarka00lars/page/221 221–243] |url=https://archive.org/details/evolutionremarka00lars/page/221 }}</ref>

The American biologist [[Sewall Wright]], who had a background in [[animal breeding]] experiments, focused on combinations of interacting genes, and the effects of [[inbreeding]] on small, relatively isolated populations that exhibited genetic drift. In 1932 Wright introduced the concept of an [[Fitness landscape|adaptive landscape]] and argued that genetic drift and inbreeding could drive a small, isolated sub-population away from an adaptive peak, allowing natural selection to drive it towards different adaptive peaks.{{citation needed|date=January 2020}}

The work of Fisher, Haldane and Wright founded the discipline of population genetics. This integrated natural selection with Mendelian genetics, which was the critical first step in developing a unified theory of how evolution worked.<ref name="Bowler325-339"/><ref name="Larson221-243"/> [[John Maynard Smith]] was Haldane's pupil, whilst [[W. D. Hamilton]] was influenced by the writings of Fisher. The American [[George R. Price]] worked with both Hamilton and Maynard Smith. American [[Richard Lewontin]] and Japanese [[Motoo Kimura]] were influenced by Wright and Haldane.{{citation needed|date=January 2020}}

===Modern synthesis===
{{main |Modern synthesis (20th century)}}

The mathematics of population genetics were originally developed as the beginning of the [[Modern synthesis (20th century)|modern synthesis]]. Authors such as Beatty<ref>{{cite book |last=Beatty |first=John |title=Integrating Scientific Disciplines |volume=2 |publisher=Springer Netherlands |isbn=9789024733422 |pages=125–135 |chapter=The Synthesis and the Synthetic Theory|doi=10.1007/978-94-010-9435-1_7 |series=Science and Philosophy |year=1986 }}</ref> have asserted that population genetics defines the core of the modern synthesis. For the first few decades of the 20th century, most field naturalists continued to believe that [[Lamarckism]] and [[orthogenesis]] provided the best explanation for the complexity they observed in the living world.<ref>{{cite book |editor1-last=Mayr |editor1-first=Ernst |editor-link=Ernst Mayr |editor2-first=William B. |editor2-last=Provine |title=The Evolutionary synthesis : perspectives on the unification of biology |date=1998 |publisher=Harvard University Press |location=Cambridge, Massachusetts |isbn=9780674272262 |pages=295–298 |edition=[New ed].}}</ref> During the modern synthesis, these ideas were purged, and only evolutionary causes that could be expressed in the mathematical framework of population genetics were retained.<ref name="Provine88">{{cite book |last=Provine |first=W. B. |year=1988 |title=Evolutionary progress |chapter= Progress in evolution and meaning in life |pages=49–79 |publisher=University of Chicago Press}}</ref> Consensus was reached as to which evolutionary factors might influence evolution, but not as to the relative importance of the various factors.<ref name="Provine88" />

[[Theodosius Dobzhansky]], a postdoctoral worker in [[T. H. Morgan]]'s lab, had been influenced by the work on [[genetic diversity]] by Russian geneticists such as [[Sergei Chetverikov]]. He helped to bridge the divide between the foundations of [[microevolution]] developed by the population geneticists and the patterns of [[macroevolution]] observed by field biologists, with his 1937 book ''[[Genetics and the Origin of Species]]''. Dobzhansky examined the genetic diversity of wild populations and showed that, contrary to the assumptions of the population geneticists, these populations had large amounts of genetic diversity, with marked differences between sub-populations. The book also took the highly mathematical work of the population geneticists and put it into a more accessible form. Many more biologists were influenced by population genetics via Dobzhansky than were able to read the highly mathematical works in the original.<ref name="Provine78">{{cite journal |last=Provine |first=William B. |year=1978 |title=The role of mathematical population geneticists in the evolutionary synthesis of the 1930s and 1940s |journal=Studies of the History of Biology |volume=2 |pages=167–192|pmid=11610409 }}</ref>

In Great Britain [[E. B. Ford]], the pioneer of [[ecological genetics]],<ref>{{cite book |last=Ford |first=E. B. |author-link=E.B. Ford |orig-year=1964 |edition=4th |year=1975 |title=Ecological genetics |publisher=Chapman and Hall |location=London |pages=1ff}}</ref> continued throughout the 1930s and 1940s to empirically demonstrate the power of selection due to ecological factors including the ability to maintain genetic diversity through genetic [[polymorphism (biology)|polymorphisms]] such as human [[blood type]]s. Ford's work, in collaboration with Fisher, contributed to a shift in emphasis during the modern synthesis towards natural selection as the dominant force.<ref name="Bowler325-339"/><ref name="Larson221-243"/><ref>{{cite book |last=Mayr |first=Ernst |author-link=Ernst Mayr |year=1988 |title= Toward a New Philosophy of Biology: Observations of an Evolutionist |location=Cambridge, Massachusetts |publisher=[[Harvard University Press|Belknap Press of Harvard University Press]] |page=402 |isbn=978-0-674-89665-9 |title-link=Toward a New Philosophy of Biology }}</ref><ref>{{cite book |editor-last=Mayr |editor-first=Ernst |editor-link=Ernst Mayr |editor2-last=Provine |editor2-first=William B. |title=The Evolutionary Synthesis : perspectives on the unification of biology |date=1998 |publisher=Harvard University Press |location=Cambridge, Massachusetts |isbn=9780674272262 |pages=338–341 |edition=[New ed].}}</ref><!--ref name="Provine88"/-->

===Neutral theory and origin-fixation dynamics===

The original, modern synthesis view of population genetics assumes that mutations provide ample raw material, and focuses only on the change in [[allele frequency|frequency of alleles]] within [[population]]s.<ref name="McCandlish-2014">{{cite journal |last1=McCandlish |first1=David M. |last2=Stoltzfus |first2=Arlin |title=Modeling Evolution Using the Probability of Fixation: History and Implications |journal=The Quarterly Review of Biology |date=September 2014 |volume=89 |issue=3 |pages=225–252 |doi=10.1086/677571|pmid=25195318 |s2cid=19619966 }}</ref> The main processes influencing allele frequencies are [[natural selection]], [[genetic drift]], [[gene flow]] and recurrent [[mutation]]. Fisher and Wright had some fundamental disagreements about the relative roles of selection and drift.<ref name="Crow 2010">{{cite journal |last=Crow |first=James F. |title=Wright and Fisher on Inbreeding and Random Drift |journal=Genetics |volume=184 |issue=3 |year=2010 |pages=609–611 |issn=0016-6731 |doi=10.1534/genetics.109.110023|pmid=20332416 |pmc=2845331 |doi-access=free }}</ref>
The availability of molecular data on all genetic differences led to the [[neutral theory of molecular evolution]]. In this view, many mutations are deleterious and so never observed, and most of the remainder are neutral, i.e. are not under selection. With the fate of each neutral mutation left to chance (genetic drift), the direction of evolutionary change is driven by which mutations occur, and so cannot be captured by models of change in the frequency of (existing) alleles alone.<ref name="McCandlish-2014" /><ref name="CasillasBarbadilla2017">{{cite journal |last1=Casillas |first1=Sònia |last2=Barbadilla |first2=Antonio |title=Molecular Population Genetics |journal=Genetics |date=2017 |volume=205 |issue=3 |pages=1003–1035 |doi=10.1534/genetics.116.196493|pmid=28270526 |pmc=5340319 }}</ref>

The origin-fixation view of population genetics generalizes this approach beyond strictly neutral mutations, and sees the rate at which a particular change happens as the product of the mutation rate and the [[Fixation (population genetics)|fixation probability]].<ref name="McCandlish-2014" />

==Four processes==

===Selection===
[[Natural selection]], which includes [[sexual selection]], is the fact that some [[trait (biology)|traits]] make it more likely for an [[organism]] to survive and [[reproduction|reproduce]]. Population genetics describes natural selection by defining [[fitness (biology)|fitness]] as a [[propensity probability|propensity or probability]] of survival and reproduction in a particular environment. The fitness is normally given by the symbol '''w'''=1-'''s''' where '''s''' is the [[selection coefficient]]. Natural selection acts on [[phenotype]]s, so population genetic models assume relatively simple relationships to predict the phenotype and hence fitness from the [[allele]] at one or a small number of loci. In this way, natural selection converts differences in the fitness of individuals with different phenotypes into changes in allele frequency in a population over successive generations.{{citation needed|date=January 2021}}

Before the advent of population genetics, many biologists doubted that small differences in fitness were sufficient to make a large difference to evolution.<ref name="Provine78"/> Population geneticists addressed this concern in part by comparing selection to [[genetic drift]]. Selection can overcome genetic drift when '''s''' is greater than 1 divided by the [[effective population size]]. When this criterion is met, the probability that a new advantageous mutant becomes [[fixation (population genetics)|fixed]] is approximately equal to '''2s'''.<ref>{{cite journal |last=Haldane |first=J. B. S. |author-link=J. B. S. Haldane |title=A Mathematical Theory of Natural and Artificial Selection, Part V: Selection and Mutation |journal=[[Mathematical Proceedings of the Cambridge Philosophical Society]] |year=1927 |volume=23 |pages=838–844 |bibcode=1927PCPS...23..838H |doi=10.1017/S0305004100015644 |issue=7|s2cid=86716613 }}</ref><ref>{{Cite journal |last1=Orr |first1=H. A. |title=The population genetics of beneficial mutations |doi=10.1098/rstb.2009.0282 |journal=Philosophical Transactions of the Royal Society B: Biological Sciences |volume=365 |issue=1544 |pages=1195–1201 |year=2010 |pmid=20308094|pmc=2871816}}</ref> The time until fixation of such an allele  is approximately <math>(2 log(sN)+\gamma)/s</math>.<ref>{{cite journal |last1=Hermisson |first1=J. |last2=Pennings |first2=P. S. |title=Soft sweeps: molecular population genetics of adaptation from standing genetic variation |journal=Genetics |year=2005 |volume=169 |pages=2335–2352 |doi=10.1534/genetics.104.036947 |pmid=15716498 |issue=4 |pmc=1449620 }}</ref>

====Dominance====

[[Dominance (genetics)|Dominance]] means that the phenotypic and/or fitness effect of one allele at a locus depends on which allele is present in the second copy for that locus. Consider three genotypes at one locus, with the following fitness values<ref>{{cite book |last=Gillespie |first=John |author-link=John H. Gillespie |title=Population Genetics: A Concise Guide |edition=2nd |publisher=Johns Hopkins University Press |year=2004 |isbn=978-0-8018-8008-7}}</ref>

{|class="wikitable"
 |-
 |Genotype:
 |A<sub>1</sub>A<sub>1</sub>
 |A<sub>1</sub>A<sub>2</sub>
 |A<sub>2</sub>A<sub>2</sub>
 |-
 |Relative fitness:
 |1
 |1-hs
 |1-s
 |}
{{Glossary infobox
| align         = right
| width         = 452px
| collapse      = 
| header        = Population genetics glossary
| definitions   = 
* '''[[species]]''' – a group of closely related organisms which, if sexual, are capable of interbreeding and producing fertile offspring
* '''[[population]]''' – the set of individuals of a particular species in a given area 
* '''[[gene pool]]''' – the collective genetic information contained within a population of sexually reproducing organisms; ignores [[linkage disequilibrium]]
* '''[[allele frequency]]''' – the frequency or proportion of a particular allele of a gene within a population
}}
s is the [[selection coefficient]] and h is the dominance coefficient. The value of h yields the following information:

{|class="wikitable"
 |-
 |h=0
 |A<sub>1</sub> dominant, A<sub>2</sub> recessive
 |-
 |h=1
 |A<sub>2</sub> dominant, A<sub>1</sub> recessive
 |-
 |0<h<1
 |incomplete dominance
 |-
 |h<0
 |[[overdominance]]
 |-
 |h>1
 |[[Underdominance]]
 |}

====Epistasis====
[[File:Synergistic versus antagonistic epistasis.svg|thumb |200px |The [[logarithm]] of fitness as a function of the number of deleterious mutations. Synergistic epistasis is represented by the red line - each subsequent deleterious mutation has a larger proportionate effect on the organism's fitness. Antagonistic epistasis is in blue. The black line shows the non-epistatic case, where fitness is the [[Product (mathematics)|product]] of the contributions from each of its loci.]]

[[Epistasis]] means that the phenotypic and/or fitness effect of an allele at one locus depends on which alleles are present at other loci. Selection does not act on a single locus, but on a phenotype that arises through development from a complete genotype.<ref>{{cite journal |last=Miko |first=I. |date=2008 |title=Epistasis: Gene interaction and phenotype effects |journal=Nature Education |volume=1 |issue=1 |page=197 |url=http://www.nature.com/scitable/topicpage/epistasis-gene-interaction-and-phenotype-effects-460}}</ref> However, many population genetics models of sexual species are "single locus" models, where the fitness of an individual is calculated as the [[product (mathematics)|product]] of the contributions from each of its loci—effectively assuming no epistasis.

In fact, the [[fitness landscape|genotype to fitness landscape]] is more complex. Population genetics must either model this complexity in detail, or capture it by some simpler average rule. Empirically, beneficial mutations tend to have a smaller fitness benefit when added to a genetic background that already has high fitness: this is known as diminishing returns epistasis.<ref>{{cite journal |last1=Berger |first1=D. |last2=Postma |first2=E. |title=Biased Estimates of Diminishing-Returns Epistasis? Empirical Evidence Revisited |journal=Genetics |date=13 October 2014 |volume=198 |issue=4 |pages=1417–1420 |doi=10.1534/genetics.114.169870 |pmid=25313131 |pmc=4256761}}</ref> When deleterious mutations also have a smaller fitness effect on high fitness backgrounds, this is known as "synergistic epistasis". However, the effect of deleterious mutations tends on average to be very close to multiplicative, or can even show the opposite pattern, known as "antagonistic epistasis".<ref>{{cite journal |last1=Kouyos |first1=Roger D. |last2=Silander |first2=Olin K. |last3=Bonhoeffer |first3=Sebastian |title=Epistasis between deleterious mutations and the evolution of recombination |journal=Trends in Ecology & Evolution |date=June 2007 |volume=22 |issue=6 |pages=308–315 |doi=10.1016/j.tree.2007.02.014|pmid=17337087 |bibcode=2007TEcoE..22..308K }}</ref>

Synergistic epistasis is central to some theories of the purging of [[genetic load|mutation load]]<ref>{{cite journal |last1=Crow |first1=J. F. |title=The high spontaneous mutation rate: is it a health risk? |journal=Proceedings of the National Academy of Sciences of the United States of America |date=5 August 1997 |volume=94 |issue=16 |pages=8380–8386 |pmid=9237985 |doi=10.1073/pnas.94.16.8380 |pmc=33757|bibcode=1997PNAS...94.8380C |doi-access=free }}</ref> and to the [[evolution of sexual reproduction]].

===Mutation===
{{Main |Mutation}}
[[File:Drosophila melanogaster - side (aka).jpg|thumb|right |240px |''Drosophila melanogaster'']]

The genetic process of [[mutation]] takes place within an individual, resulting in heritable changes to the genetic material. This process is often characterized by a description of the starting and ending states, or the kind of change that has happened at the level of DNA (e.g,. a T-to-C mutation, a 1-bp deletion), of genes or proteins (e.g., a null mutation, a loss-of-function mutation), or at a higher phenotypic level (e.g., red-eye mutation). Single-nucleotide changes are frequently the most common type of mutation, but many other types of [[mutation]] are possible, and they occur at widely varying rates that may show systematic asymmetries or biases ([[mutation bias]]).

<!-- preserved from previous version--> 
Mutations can involve large sections of DNA becoming [[gene duplication|duplicated]], usually through [[genetic recombination]].<ref>{{Cite journal |doi=10.1038/nrg2593 |pmid=19597530 |volume=10 |issue=8 |pages=551–564 |last1=Hastings |first1=P. J. |title=Mechanisms of change in gene copy number |journal=Nature Reviews Genetics |year=2009 |last2=Lupski |first2=J. R. |last3=Rosenberg |first3=S. M. |last4=Ira |first4=G. |pmc=2864001 }}</ref> This leads to [[copy-number variation]] within a population. Duplications are a major source of raw material for evolving new genes.<ref>{{cite journal |first1=Long |last1=M. |last2=Betrán |first2=E. |last3=Thornton |first3=K. |last4=Wang |first4=W. |title=The origin of new genes: glimpses from the young and old |journal=Nat. Rev. Genet. |volume=4 |issue=11 |pages=865–75 |date=November 2003 |pmid=14634634 |doi=10.1038/nrg1204 |s2cid=33999892 }}</ref> Other types of mutation occasionally create new genes from previously noncoding DNA.<ref>{{cite journal |last1=Liu |first1=N. |last2=Okamura |first2=K. |last3=Tyler |first3=D. M. |last4=Phillips |last5=Chung |last6=Lai |title=The evolution and functional diversification of animal microRNA genes |journal=Cell Research |year=2008 |volume=18 |pages=985–996 |doi=10.1038/cr.2008.278 |pmid=18711447 |issue=10 |pmc=2712117 }}</ref><ref>{{cite journal |last1=McLysaght |first1=Aoife |last2=Hurst |first2=Laurence D. |title=Open questions in the study of de novo genes: what, how and why |journal=Nature Reviews Genetics |date=25 July 2016 |volume=17 |issue=9 |pages=567–578 |doi=10.1038/nrg.2016.78 |pmid=27452112 |s2cid=6033249 |url=https://zenodo.org/record/3451105 }}{{Dead link|date=December 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

In the [[Mutation#Distribution_of_fitness_effects_(DFE)|distribution of fitness effects (DFE)]] for new mutations, only a minority of mutations are beneficial. Mutations with gross effects are typically deleterious. Studies in the fly ''[[Drosophila melanogaster]]'' suggest that if a mutation changes a protein produced by a gene, this will probably be harmful, with about 70 percent of these mutations having damaging effects, and the remainder being either neutral or weakly beneficial.<ref name="SawyerParsch2007">{{cite journal |last1=Sawyer |first1=S. A. |last2=Parsch |first2=J. |last3=Zhang |first3=Z.|last4=Hartl |first4=D. L. |title=Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila |journal=Proceedings of the National Academy of Sciences |volume=104 |issue=16 |year=2007 |pages=6504–6510 |issn=0027-8424 |doi=10.1073/pnas.0701572104|pmid=17409186 |pmc=1871816 |bibcode=2007PNAS..104.6504S |doi-access=free }}</ref> 

<!-- explain the two roles, starting with mutation pressure --> 
This biological process of mutation is represented in population-genetic models in one of two ways, either as a deterministic pressure of recurrent mutation on allele frequencies, or a source of variation. In deterministic theory, evolution begins with a predetermined set of alleles and proceeds by shifts in continuous frequencies, as if the population is infinite. The occurrence of mutations in individuals is represented by a population-level "force" or "pressure" of mutation, i.e., the force of innumerable events of mutation with a scaled magnitude u applied to shifting frequencies f(A1) to f(A2). For instance, in the classic [[mutation–selection balance]] model,<ref name="CrowKimura1970">{{cite book|first1=James F.|last1=Crow|first2=Motoo|last2=Kimura|title=An Introduction to Population Genetics Theory|date=1970|publisher=Blackburn Press|location=New Jersey|isbn=9781932846126|edition=[Reprint]}}</ref> the force of mutation pressure pushes the frequency of an allele upward, and selection against its deleterious effects pushes the frequency downward, so that a balance is reached at equilibrium, given (in the simplest case) by f = u/s.

This concept of mutation pressure is mostly useful for considering the implications of deleterious mutation, such as the mutation load and its implications for the evolution of the mutation rate.<ref name=Lynch2010>{{cite journal|last1=Lynch|first1=Michael|title=Evolution of the mutation rate|journal=Trends in Genetics|date=August 2010|volume=26|issue=8|pages=345–352|doi=10.1016/j.tig.2010.05.003|pmid=20594608|pmc=2910838}}</ref> Transformation of populations by mutation pressure is unlikely. Haldane<ref name=Haldane1932>{{cite book | author=J. B. S. Haldane | year=1932 | title=The Causes of Evolution | publisher=Longmans, Green and Co., New York }}</ref> argued that it would require high mutation rates unopposed by selection, and Kimura<ref name=Kimura1980>{{cite journal | author=M. Kimura | year=1980 | title=Average time until fixation of a mutant allele in a finite population under continued mutation pressure: Studies by analytical, numerical, and pseudo-sampling methods | journal=Proc Natl Acad Sci U S A | volume=77 | issue=1 | pages=522–526 | doi=10.1073/pnas.77.1.522 | pmid=16592764 | pmc=348304 | bibcode=1980PNAS...77..522K | doi-access=free }}</ref> concluded even more pessimistically that even this was unlikely, as the process would take too long (see [[Bias_in_the_introduction_of_variation#Evolution_by_mutation_pressure | evolution by mutation pressure]]).

<!-- cover the issue of mutational loss of unused organs --> 
However, [[Bias_in_the_introduction_of_variation#Evolution_by_mutation_pressure | evolution by mutation pressure]] is possible under some circumstances and has long been suggested as a possible cause for the loss of unused traits.<ref name=Haldane1933>{{cite journal |last=Haldane |first=J. B. S. |author-link=J. B. S. Haldane |year=1933 |title=The Part Played by Recurrent Mutation in Evolution |journal=American Naturalist |volume=67 |pages=5–19 |jstor=2457127 |doi=10.1086/280465 |issue=708|bibcode=1933ANat...67....5H |s2cid=84059440 }}</ref> 
For example, [[pigment]]s are no longer useful when animals live in the darkness of caves, and tend to be lost.<ref>{{Cite journal |doi=10.1016/j.cub.2007.01.051 |pmid=17306543 |volume=17 |issue=5 |pages=452–454 |last1=Protas |first1=Meredith |title=Regressive evolution in the Mexican cave tetra, Astyanax mexicanus |journal=Current Biology |year=2007 |last2=Conrad |first2=M. |last3=Gross |first3=J. B. |last4=Tabin |first4=C. |last5=Borowsky |first5=R |pmc=2570642 |bibcode=2007CBio...17..452P }}</ref> An experimental example involves the loss of sporulation in experimental populations of ''B. subtilis''. Sporulation is a complex trait encoded by many loci, such that the mutation rate for loss of the trait was estimated as an unusually high value, <math>\mu = 0.003</math>.<ref name=Maughan2007>{{cite journal | author=H. Maughan, J. Masel, C. W. Birky, Jr. and W. L. Nicholson | year=2007 | title=The roles of mutation accumulation and selection in loss of sporulation in experimental populations of Bacillus subtilis | journal=Genetics | volume=177 | issue=2 | pages=937–48 | doi=10.1534/genetics.107.075663| pmid=17720926 | pmc=2034656 }}</ref> Loss of sporulation in this case can occur by recurrent mutation, without requiring selection for the loss of sporulation ability. When there is no selection for loss of function, the speed at which loss evolves depends more on the mutation rate than it does on the [[effective population size]],<ref>{{cite journal |last1=Masel |first1=J. |author-link=Joanna Masel |last2=King |first2=O. D. |last3=Maughan |first3=H. |title=The loss of adaptive plasticity during long periods of environmental stasis |doi= 10.1086/510212 |journal=American Naturalist |volume=169 |issue=1 |pages=38–46 |year=2007 |pmid=17206583 |pmc=1766558 |bibcode=2007ANat..169...38M }}</ref> indicating that it is driven more by mutation than by genetic drift.

<!-- generalize and introduce the introduction process --> 
The role of mutation as a source of novelty is different from these classical models of mutation pressure. 
When population-genetic models include a rate-dependent process of mutational introduction or origination, i.e., a process that introduces new alleles including neutral and beneficial ones, then the properties of mutation may have a more direct impact on the rate and direction of evolution, even if the rate of mutation is very low.<ref name=Gomez2020>{{cite journal | author=K. Gomez, J. Bertram and J. Masel | year=2020 | title=Mutation bias can shape adaptation in large asexual populations experiencing clonal interference | journal=Proc. R. Soc. B | volume=287 | issue=1937 | pages=20201503 | doi=10.1098/rspb.2020.1503| pmid=33081612 | pmc=7661309 }}</ref><ref name=Cano2022>{{cite journal | author=A. V. Cano, H. Rozhonova, A. Stoltzfus, D. M. McCandlish and J. L. Payne | date=2022-02-10 | title=Mutation bias shapes the spectrum of adaptive substitutions | journal=Proc Natl Acad Sci U S A | volume=119 | issue=7 | doi=10.1073/pnas.2119720119| doi-access=free | pmid=35145034 | pmc=8851560 | bibcode=2022PNAS..11919720C }}</ref> That is, the spectrum of mutation may become very important, particularly [[mutation bias|mutation biases]], predictable differences in the rates of occurrence for different types of mutations, because [[bias in the introduction of variation]] can impose biases on the course of evolution.<ref>{{cite journal |last1=Stoltzfus |first1=A. |last2=Yampolsky |first2=L. Y. |year=2009 |title=Climbing Mount Probable: Mutation as a Cause of Nonrandomness in Evolution |journal=Journal of Heredity |volume=100 |pages=637–647 |doi=10.1093/jhered/esp048 |pmid=19625453 |issue=5 |doi-access=free }}</ref>

Mutation plays a key role in other classical and recent theories including [[Muller%27s ratchet]], [[subfunctionalization]], Eigen's concept of an [[error catastrophe]] and Lynch's [[Evolution_of_biological_complexity#Mutational_hazard_hypothesis|mutational hazard hypothesis]].

===Genetic drift===
{{Main |Genetic drift}}

''Genetic drift'' is a change in [[Allele frequency|allele frequencies]] caused by [[Sampling (statistics)|random sampling]].<ref name="Masel 2011">{{Cite journal |volume=21 |pages=R837–R838 |last=Masel |first=J. |author-link=Joanna Masel |title=Genetic drift |journal=Current Biology |year=2011 |doi=10.1016/j.cub.2011.08.007 |issue=20 |pmid=22032182|doi-access=free |bibcode=2011CBio...21.R837M }}</ref> That is, the alleles in the offspring are a random sample of those in the parents.<ref>{{cite book |last=Futuyma |first=Douglas |title=Evolutionary Biology |publisher=[[Sinauer Associates]] |year=1998 |isbn=978-0-87893-189-7 |page=Glossary}}</ref> Genetic drift may cause gene variants to disappear completely, and thereby reduce genetic variability. In contrast to natural selection, which makes gene variants more common or less common depending on their reproductive success,<ref name=avers>{{Cite book |last=Avers |first=Charlotte |year=1989 |title=Process and Pattern in Evolution |publisher=Oxford University Press }}</ref> the changes due to genetic drift are not driven by environmental or adaptive pressures, and are equally likely to make an allele more common as less common.

The effect of genetic drift is larger for alleles present in few copies than when an allele is present in many copies. The population genetics of genetic drift are described using either [[branching process]]es or a [[diffusion equation]] describing changes in allele frequency.<ref>{{Cite journal |volume=188 |pages=783–785 |last=Wahl |first=L. M. |title=Fixation when N and s Vary: Classic Approaches Give Elegant New Results |journal=Genetics |year=2011 |doi=10.1534/genetics.111.131748 |issue=4 |pmid=21828279 |pmc=3176088}}</ref> These approaches are usually applied to the Wright-Fisher and [[Moran process|Moran]] models of population genetics. Assuming genetic drift is the only evolutionary force acting on an allele, after t generations in many replicated populations, starting with allele frequencies of p and q, the variance in allele frequency across those populations is

:<math>
V_t \approx pq\left(1-\exp\left\{-\frac{t}{2N_e} \right\}\right).
</math><ref>{{cite book |last1=Barton |first1=Nicholas H. |last2=Briggs |first2=Derek E. G. |last3=Eisen |first3=Jonathan A. |last4=Goldstein |first4=David B. |last5=Patel |first5=Nipam H. |title=Evolution |publisher=Cold Spring Harbor Laboratory Press |year=2007 |isbn=978-0-87969-684-9 |page=417}}</ref>

[[Ronald Fisher]] held the view that genetic drift plays at the most a minor role in evolution, and this remained the dominant view for several decades. No population genetics perspective have ever given genetic drift a central role by itself, but some have made genetic drift important in combination with another non-selective force. The [[shifting balance theory]] of [[Sewall Wright]] held that the combination of population structure and genetic drift was important. [[Motoo Kimura]]'s [[neutral theory of molecular evolution]] claims that most genetic differences within and between populations are caused by the combination of neutral mutations and genetic drift.<ref name="Futuyma 1998 320">{{cite book |last=Futuyma |first=Douglas |title=Evolutionary Biology |publisher=[[Sinauer Associates]] | year=1998 |isbn=978-0-87893-189-7 |page=320}}</ref>

The role of genetic drift by means of [[sampling error]] in evolution has been criticized by [[John H Gillespie]]<ref>{{cite journal |last=Gillespie |first=J. H. |title=Genetic Drift in an Infinite Population: The Pseudohitchhiking Model |journal=Genetics |volume=155 |issue=2 |pages=909–919 |year=2000 |doi=10.1093/genetics/155.2.909 |pmid=10835409 |pmc=1461093}}</ref> and [[Will Provine]],<ref>{{cite book |last=Provine |first=William B. |title=The "Random Genetic Drift" Fallacy |publisher=CreateSpace}}</ref> who argue that selection on linked sites is a more important stochastic force, doing the work traditionally ascribed to genetic drift by means of sampling error. The mathematical properties of genetic draft are different from those of genetic drift.<ref>{{cite journal |last1=Neher |first1=Richard A. |last2=Shraiman |first2=Boris I. |date=August 2011 |title=Genetic Draft and Quasi-Neutrality in Large Facultatively Sexual Populations |journal=Genetics |volume=188 |issue=4 |pages=975–996 |doi=10.1534/genetics.111.128876 |issn=0016-6731 |pmc=3176096 |pmid=21625002|arxiv=1108.1635 }}</ref> The direction of the random change in allele frequency is [[autocorrelation|autocorrelated]] across generations.<ref name="Masel 2011" />

===Gene flow===
[[File:Gene flow final.png|thumb|left|Gene flow is the transfer of [[allele]]s from one [[population]] to another population through immigration of individuals. In this example, one of the birds from population A [[immigrate]]s to population B, which has fewer of the dominant alleles, and through mating incorporates its alleles into the other population.]]
{{Main |Gene flow}}

Because of physical barriers to migration, along with the limited tendency for individuals to move or spread ([[wikt:vagility|vagility]]), and tendency to remain or come back to natal place ([[philopatry]]), natural populations rarely all interbreed as may be assumed in theoretical random models ([[panmixy]]).<ref>{{cite journal |last1=Buston |first1=P. M. |last2=Pilkington |first2=J. G. |year=2007 |title=Are clownfish groups composed of close relatives? An analysis of microsatellite DNA vraiation in ''Amphiprion percula'' |journal=Molecular Ecology |volume=12 |pages=733–742 |pmid=12675828 |issue=3 | doi=10.1046/j.1365-294X.2003.01762.x |s2cid=35546810 |display-authors=etal}}</ref> There is usually a geographic range within which individuals are more closely [[coefficient of relatedness|related]] to one another than those randomly selected from the general population. This is described as the extent to which a population is genetically structured.<ref>{{cite journal |last1=Repaci |first1=V. |last2=Stow |first2=A. J. |last3=Briscoe |first3=D. A. |year=2007 |title=Fine-scale genetic structure, co-founding and multiple mating in the Australian allodapine bee (''Ramphocinclus brachyurus'') |journal=Journal of Zoology |volume=270 |issue=4 |pages=687–691 |doi=10.1111/j.1469-7998.2006.00191.x}}</ref>

[[File:Greatwall large.jpg|thumb|The [[Great Wall of China]] is an obstacle to gene flow of some terrestrial species.<ref name="Su Qu 2003"/>]]

Genetic structuring can be caused by migration due to historical [[climate change (general concept)|climate change]], species [[range expansion]] or current availability of [[habitat]]. Gene flow is hindered by mountain ranges, oceans and deserts or even human-made structures such as the [[Great Wall of China]], which has hindered the flow of plant genes.<ref name="Su Qu 2003">{{cite journal |last1=Su |first1=H. |last2=Qu |first2=L.-J. |last3=He |first3=K. |last4=Zhang |first4=Z. |last5=Wang |first5=J|last6=Chen |first6=Z. |last7=Gu |first7=H. |title=The Great Wall of China: a physical barrier to gene flow? |journal=Heredity |volume=90 |issue=3 |year=2003 |pages=212–219 |issn=0018-067X |doi=10.1038/sj.hdy.6800237|pmid=12634804 |s2cid=13367320 }}</ref>

[[Gene flow]] is the exchange of genes between populations or species, breaking down the structure. Examples of gene flow within a species include the migration and then breeding of organisms, or the exchange of [[pollen]]. Gene transfer between species includes the formation of [[Hybrid (biology)|hybrid]] organisms and [[horizontal gene transfer]]. Population genetic models can be used to identify which populations show significant genetic isolation from one another, and to reconstruct their history.<ref>{{cite journal |last=Gravel |first=S. |title=Population Genetics Models of Local Ancestry |year=2012 |bibcode=2012arXiv1202.4811G |volume=1202 |pages=607–619 |arxiv=1202.4811 |doi=10.1534/genetics.112.139808 |pmid=22491189 |pmc=3374321 |journal=Genetics |issue=2}}</ref>

Subjecting a population to isolation leads to [[inbreeding depression]]. Migration into a population can introduce new genetic variants,<ref>{{cite journal |last1=Morjan |first1=C. |last2=Rieseberg |first2=L. |title=How species evolve collectively: implications of gene flow and selection for the spread of advantageous alleles |journal=Molecular Ecology |volume=13 |issue=6 |pages=1341–56 |year=2004 |pmid=15140081 |doi=10.1111/j.1365-294X.2004.02164.x |pmc=2600545 |bibcode=2004MolEc..13.1341M }}</ref> potentially contributing to [[evolutionary rescue]]. If a significant proportion of individuals or gametes migrate, it can also change allele frequencies, e.g. giving rise to [[Genetic load#Migration load|migration load]].<ref>{{cite journal |last1=Bolnick |first1=Daniel I. |last2=Nosil |first2=Patrik |title=Natural Selection in Populations Subject to a Migration Load |journal=Evolution |date=September 2007 |volume=61 |issue=9 |pages=2229–2243 |doi=10.1111/j.1558-5646.2007.00179.x |pmid=17767592 |s2cid=25685919 |doi-access=free}}</ref>

In the presence of gene flow, other [[reproductive isolation|barriers to hybridization]] between two diverging populations of an [[outcrossing]] species are required for the populations to [[speciation|become new species]].

====Horizontal gene transfer====
[[File:Tree Of Life (with horizontal gene transfer).svg|thumb|Current tree of life showing vertical and horizontal gene transfers]]
{{Main |Horizontal gene transfer}}

Horizontal gene transfer is the transfer of genetic material from one organism to another organism that is not its offspring; this is most common among [[prokaryote]]s.<ref name="Boucher Douady 2003">{{cite journal |last1=Boucher |first1=Yan |last2=Douady |first2=Christophe J. |last3=Papke |first3=R. Thane |last4=Walsh |first4=David A. |last5=Boudreau |first5=Mary Ellen R. |last6=Nesbø|first6=Camilla L. |last7=Case |first7=Rebecca J. |last8=Doolittle |first8=W. Ford|title=Lateral Gene Transfer and the Origins of Prokaryotic Groups |journal=Annual Review of Genetics |volume=37 |issue=1 |year=2003 |pages=283–328 |issn=0066-4197 |doi=10.1146/annurev.genet.37.050503.084247|pmid=14616063 }}</ref> In medicine, this contributes to the spread of [[antibiotic resistance]], as when one bacteria acquires resistance genes it can rapidly transfer them to other species.<ref>{{cite journal |last=Walsh |first=T. |title=Combinatorial genetic evolution of multiresistance |journal=Current Opinion in Microbiology |volume=9 |issue=5 |pages=476–82 |year=2006 |pmid=16942901 |doi=10.1016/j.mib.2006.08.009}}</ref> Horizontal transfer of genes from bacteria to eukaryotes such as the yeast ''[[Saccharomyces cerevisiae]]'' and the adzuki bean beetle ''[[Callosobruchus chinensis]]'' may also have occurred.<ref name="Kondo Nikoh 2002">{{cite journal |last1=Kondo |first1=N. |last2=Nikoh |first2=N. |last3=Ijichi |first3=N. |last4=Shimada |first4=M. |last5=Fukatsu |first5=T. |title=Genome fragment of Wolbachia endosymbiont transferred to X chromosome of host insect |journal=Proceedings of the National Academy of Sciences |volume=99 |issue=22 |year=2002 |pages=14280–14285 |issn=0027-8424 |doi=10.1073/pnas.222228199|pmid=12386340 |pmc=137875 |bibcode=2002PNAS...9914280K |doi-access=free }}</ref><ref>{{cite journal |last=Sprague |first=G. |title=Genetic exchange between kingdoms |journal=Current Opinion in Genetics & Development |volume=1 |issue=4 |pages=530–533 |year=1991 |pmid=1822285 |doi=10.1016/S0959-437X(05)80203-5}}</ref> An example of larger-scale transfers are the eukaryotic [[Bdelloidea|bdelloid rotifers]], which appear to have received a range of genes from bacteria, fungi, and plants.<ref name="Gladyshev Meselson 2008">{{cite journal |last1=Gladyshev |first1=E. A. |last2=Meselson |first2=M. |last3=Arkhipova |first3=I. R. |title=Massive Horizontal Gene Transfer in Bdelloid Rotifers |journal=Science |volume=320 |issue=5880 |year=2008 |pages=1210–1213 |issn=0036-8075 |doi=10.1126/science.1156407|pmid=18511688 |bibcode=2008Sci...320.1210G |s2cid=11862013 |url=http://nrs.harvard.edu/urn-3:HUL.InstRepos:3120157 }}</ref> [[Virus]]es can also carry DNA between organisms, allowing transfer of genes even across [[domain (biology)|biological domains]].<ref>{{cite journal |last1=Baldo |first1=A. |last2=McClure |first2=M. |title=Evolution and horizontal transfer of dUTPase-encoding genes in viruses and their hosts |journal=Journal of Virology |volume=73 |issue=9 |pages=7710–7721 |date=1 September 1999 |pmid=10438861 |pmc=104298 |doi=10.1128/JVI.73.9.7710-7721.1999 }}</ref> Large-scale gene transfer has also occurred between the ancestors of [[eukaryote|eukaryotic cells]] and prokaryotes, during the acquisition of [[chloroplast]]s and [[Mitochondrion|mitochondria]].<ref name="rgruqh">{{cite journal |last1=Poole |first1=A. |last2=Penny |first2=D. |title=Evaluating hypotheses for the origin of eukaryotes |journal=BioEssays |volume=29 |issue=1 |pages=74–84 |year=2007 |pmid=17187354 |doi=10.1002/bies.20516}}</ref>

==Linkage==

If all genes are in [[linkage equilibrium]], the effect of an allele at one locus can be averaged across the [[gene pool]] at other loci. In reality, one allele is frequently found in [[linkage disequilibrium]] with genes at other loci, especially with genes located nearby on the same chromosome. [[Recombination (biology)|Recombination]] breaks up this linkage disequilibrium too slowly to avoid [[genetic hitchhiking]], where an allele at one locus rises to high frequency because it is [[genetic linkage|linked]] to an allele under selection at a nearby locus. Linkage also slows down the rate of adaptation, even in sexual populations.<ref>{{cite journal |last1=Weissman |first1=D. B. |last2=Hallatschek |first2=O. |title=The Rate of Adaptation in Large Sexual Populations with Linear Chromosomes |journal=Genetics |date=15 January 2014 |volume=196 |issue=4 |pages=1167–1183 |doi=10.1534/genetics.113.160705 |pmid=24429280 |pmc=3982688}}</ref><ref>{{cite journal |last1=Weissman |first1=Daniel B. |last2=Barton |first2=Nicholas H. |last3=McVean |first3=Gil |title=Limits to the Rate of Adaptive Substitution in Sexual Populations |journal=PLOS Genetics |date=7 June 2012 |volume=8 |issue=6 |pages=e1002740 |doi=10.1371/journal.pgen.1002740 |pmid=22685419 |pmc=3369949 |doi-access=free }}</ref><ref>{{cite journal |last1=Neher |first1=R. A. |last2=Shraiman |first2=B. I. |last3=Fisher |first3=D. S. |title=Rate of Adaptation in Large Sexual Populations |journal=Genetics |date=30 November 2009 |volume=184 |issue=2 |pages=467–481 |doi=10.1534/genetics.109.109009|pmid=19948891 |pmc=2828726 |arxiv=1108.3464 }}</ref> The effect of linkage disequilibrium in slowing down the rate of adaptive evolution arises from a combination of the [[Hill–Robertson effect]] (delays in bringing beneficial mutations together) and [[background selection]] (delays in separating beneficial mutations from deleterious [[genetic hitchhiking|hitchhikers]]).

Linkage is a problem for population genetic models that treat one gene locus at a time. It can, however, be exploited as a method for detecting the action of [[natural selection]] via [[selective sweep]]s.

In the extreme case of an [[asexual reproduction|asexual population]], linkage is complete, and population genetic equations can be derived and solved in terms of a travelling [[wave]] of genotype frequencies along a simple [[fitness landscape]].<ref name="Desai">{{cite journal |last1=Desai |first1=Michael M. |last2=Fisher |first2=Daniel S. |title=Beneficial Mutation Selection Balance and the Effect of Linkage on Positive Selection |journal=Genetics |volume=176 |issue=3 |pages=1759–1798 |year=2007 |doi=10.1534/genetics.106.067678 |pmid=17483432 |pmc=1931526}}</ref> Most [[microorganisms|microbes]], such as [[bacteria]], are asexual. The population genetics of their [[adaptation]] have two contrasting regimes. When the product of the beneficial mutation rate and population size is small, asexual populations follow a "successional regime" of origin-fixation dynamics, with adaptation rate strongly dependent on this product. When the product is much larger, asexual populations follow a "concurrent mutations" regime with adaptation rate less dependent on the product, characterized by [[clonal interference]] and the appearance of a new beneficial mutation before the last one has [[Fixation (population genetics)|fixed]].

==Applications==

===Explaining levels of genetic variation===
[[neutral theory of molecular evolution|Neutral theory]] predicts that the level of [[nucleotide diversity]] in a population will be proportional to the product of the population size and the neutral mutation rate. The fact that levels of genetic diversity vary much less than population sizes do is known as the "paradox of variation".<ref>{{cite book |last=Lewontin |first=R. C. |title=The genetic basis of evolutionary change |date=1973 |publisher=Columbia University Press |location=New York |isbn=978-0231033923 |edition=[4th printing.] |url=https://archive.org/details/geneticbasisofev00lewo }}</ref> While high levels of genetic diversity were one of the original arguments in favor of neutral theory, the paradox of variation has been one of the strongest arguments against neutral theory.

It is clear that levels of genetic diversity vary greatly within a species as a function of local recombination rate, due to both [[genetic hitchhiking]] and [[background selection]]. Most current solutions to the paradox of variation invoke some level of selection at linked sites.<ref name="ellegren">{{cite journal |last1=Ellegren |first1=Hans |last2=Galtier |first2=Nicolas |title=Determinants of genetic diversity |journal=Nature Reviews Genetics |date=6 June 2016 |volume=17 |issue=7 |pages=422–433 |doi=10.1038/nrg.2016.58 |pmid=27265362 |s2cid=23531428 |url=https://hal.archives-ouvertes.fr/hal-01900639/document }}</ref> For example, one analysis suggests that larger populations have more selective sweeps, which remove more neutral genetic diversity.<ref>{{cite journal |last1=Corbett-Detig |first1=Russell B. |last2=Hartl |first2=Daniel L. |last3=Sackton |first3=Timothy B. |last4=Barton |first4=Nick H. |title=Natural Selection Constrains Neutral Diversity across A Wide Range of Species |journal=PLOS Biology |date=10 April 2015 |volume=13 |issue=4 |pages=e1002112 |doi=10.1371/journal.pbio.1002112|pmid=25859758 |pmc=4393120 |doi-access=free }}</ref> A negative correlation between mutation rate and population size may also contribute.<ref>{{cite journal |last1=Sung |first1=W. |last2=Ackerman |first2=M. S. |last3=Miller |first3=S. F. |last4=Doak |first4=T. G. |last5=Lynch |first5=M. |title=Drift-barrier hypothesis and mutation-rate evolution |journal=Proceedings of the National Academy of Sciences |date=17 October 2012 |volume=109 |issue=45 |pages=18488–18492 |doi=10.1073/pnas.1216223109|pmc=3494944 |pmid=23077252 |url=http://www.pnas.org/content/pnas/109/45/18488.full.pdf|bibcode=2012PNAS..10918488S |doi-access=free }}</ref>

Life history affects genetic diversity more than population history does, e.g. [[r/K selection theory|r-strategists]] have more genetic diversity.<ref name=ellegren />

===Detecting selection===

Population genetics models are used to infer which genes are undergoing selection. One common approach is to look for regions of high [[linkage disequilibrium]] and low genetic variance along the chromosome, to detect recent [[selective sweep]]s.

A second common approach is the [[McDonald–Kreitman test]] which compares the amount of variation within a species ([[Polymorphism (biology)|polymorphism]]) to the divergence between species (substitutions) at two types of sites; one assumed to be neutral. Typically, [[synonymous substitution|synonymous]] sites are assumed to be neutral.<ref name=charlesworth>{{cite journal |last1=Charlesworth |first1=J. Eyre-Walker |year=2008 |title=The McDonald–Kreitman Test and Slightly Deleterious Mutations |journal=Molecular Biology and Evolution |volume=25 |issue=6 |pages=1007–1015 |doi=10.1093/molbev/msn005|pmid=18195052 |doi-access=free }}</ref> Genes undergoing positive selection have an excess of divergent sites relative to polymorphic sites. The test can also be used to obtain a genome-wide estimate of the proportion of substitutions that are fixed by positive selection, α.<ref name=eyrewalker>{{cite journal |last1=Eyre-Walker |first1=A. |year=2006 |title=The genomic rate of adaptive evolution |url=http://www.zoology.wisc.edu/courses/611/Part2/Readings/3eyre-walker_tree2006.pdf |journal=Trends in Ecology and Evolution |volume=21 |issue=10 |pages=569–575 |doi=10.1016/j.tree.2006.06.015|pmid=16820244 |bibcode=2006TEcoE..21..569E }}</ref><ref name=alpha>{{Cite journal |last1=Smith |first1=N. G. C. |last2=Eyre-Walker |first2=A. |doi=10.1038/4151022a |title=Adaptive protein evolution in Drosophila |journal=Nature |volume=415 |issue=6875 |pages=1022–1024 |year=2002 |pmid=11875568 |bibcode=2002Natur.415.1022S |s2cid=4426258 }}</ref> According to the [[neutral theory of molecular evolution]], this number should be near zero. High numbers have therefore been interpreted as a genome-wide falsification of neutral theory.<ref name="Hahn">{{cite journal |last=Hahn |first=M. W. |year=2008 |title=Toward a selection theory of molecular evolution |journal=Evolution |pages=255–265 |volume=62 |issue=2 |doi=10.1111/j.1558-5646.2007.00308.x |pmid=18302709|s2cid=5986211 |doi-access=free }}</ref>

===Demographic inference===

The simplest test for population structure in a sexually reproducing, diploid species, is to see whether genotype frequencies follow Hardy-Weinberg proportions as a function of allele frequencies. For example, in the simplest case of a single locus with two [[allele]]s denoted '''A''' and '''a''' at frequencies ''p'' and ''q'', random mating predicts freq('''AA''')&nbsp;=&nbsp;''p''<sup>2</sup> for the '''AA''' [[homozygote]]s, freq('''aa''')&nbsp;=&nbsp;''q''<sup>2</sup> for the '''aa''' homozygotes, and freq('''Aa''')&nbsp;=&nbsp;2''pq'' for the [[heterozygote]]s. In the absence of population structure, Hardy-Weinberg proportions are reached within 1–2 generations of random mating. More typically, there is an excess of homozygotes, indicative of population structure. The extent of this excess can be quantified as the [[F-statistics|inbreeding coefficient, F]].

Individuals can be clustered into ''K'' subpopulations.<ref>{{Cite journal |last1=Pritchard |first1=J. K. |last2=Stephens |first2=M. |last3=Donnelly |first3=P. |date=June 2000 |title=Inference of population structure using multilocus genotype data |journal=Genetics |volume=155 |issue=2 |pages=945–959 |doi=10.1093/genetics/155.2.945 |issn=0016-6731 |pmc=1461096 |pmid=10835412}}</ref><ref>{{Cite journal |last1=Verity |first1=Robert |last2=Nichols |first2=Richard A. |date=August 2016 |title=Estimating the Number of Subpopulations (K) in Structured Populations |journal=Genetics |volume=203 |issue=4 |pages=1827–1839 |doi=10.1534/genetics.115.180992 |issn=0016-6731 |pmc=4981280 |pmid=27317680}}</ref> The degree of population structure can then be calculated using [[Fixation index|F<sub>ST</sub>]], which is a measure of the proportion of genetic variance that can be explained by population structure. Genetic population structure can then be related to geographic structure, and [[genetic admixture]] can be detected.

[[Coalescent theory]] relates genetic diversity in a sample to demographic history of the population from which it was taken. It normally assumes [[neutral theory of molecular evolution|neutrality]], and so sequences from more neutrally evolving portions of genomes are therefore selected for such analyses. It can be used to infer the relationships between species ([[Computational phylogenetics|phylogenetics]]), as well as the population structure, demographic history (e.g. [[population bottlenecks]], [[population growth]]), [[biological dispersal]], [[source–sink dynamics]]<ref>{{cite journal |last1=Manlik |first1=Oliver |last2=Chabanne |first2=Delphine |last3=Daniel |first3=Claire |last4=Bejder |first4=Lars |last5=Allen |first5=Simon J. |last6=Sherwin |first6=William B. |title=Demography and genetics suggest reversal of dolphin source–sink dynamics, with implications for conservation. |journal=Marine Mammal Science |volume=35 |issue=3 |pages=732–759 |date=13 November 2018|doi=10.1111/mms.12555|s2cid=92108810 }}</ref> and [[introgression]] within a species.

Another approach to demographic inference relies on the [[allele frequency spectrum]].<ref>{{cite journal |last1=Gutenkunst |first1=Ryan N. |last2=Hernandez |first2=Ryan D. |last3=Williamson |first3=Scott H. |last4=Bustamante |first4=Carlos D. |last5=McVean |first5=Gil |title=Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data |journal=PLOS Genetics |date=23 October 2009 |volume=5 |issue=10 |pages=e1000695 |doi=10.1371/journal.pgen.1000695 |pmid=19851460 |pmc=2760211|arxiv=0909.0925 |doi-access=free }}</ref>

===Evolution of genetic systems===

By assuming that there are loci that control the genetic system itself, population genetic models are created to describe the [[evolution of dominance]] and other forms of [[robustness (evolution)|robustness]], the [[evolution of sexual reproduction]] and recombination rates, the evolution of [[mutation rate]]s, the evolution of [[evolutionary capacitance|evolutionary capacitors]], the evolution of [[Signalling theory|costly signalling traits]], the [[evolution of ageing]], and the evolution of [[co-operation (evolution)|co-operation]]. For example, most mutations are deleterious, so the optimal [[mutation rate]] for a species may be a trade-off between the damage from a high deleterious mutation rate and the [[metabolism|metabolic]] costs of maintaining systems to reduce the mutation rate, such as DNA repair enzymes.<ref name=Sniegowski>{{cite journal |last=Sniegowski |first=P. |others=Gerrish P.; Johnson T;. Shaver A. |title=The evolution of mutation rates: separating causes from consequences |journal=BioEssays |volume=22 |issue=12 |pages=1057–1066 |year=2000 |pmid=11084621 |doi=10.1002/1521-1878(200012)22:12<1057::AID-BIES3>3.0.CO;2-W|s2cid=36771934 }}</ref>

One important aspect of such models is that selection is only strong enough to purge deleterious mutations and hence overpower mutational bias towards degradation if the selection coefficient s is greater than the inverse of the [[effective population size]]. This is known as the drift barrier and is related to the [[nearly neutral theory of molecular evolution]]. Drift barrier theory predicts that species with large effective population sizes will have highly streamlined, efficient genetic systems, while those with small population sizes will have bloated and complex [[genome]]s containing for example [[intron]]s and [[transposable element]]s.<ref>{{cite journal |last1=Lynch |first1=Michael |last2=Conery |first2=John S. |year=2003 |title=The origins of genome complexity |journal=[[Science (journal)|Science]] |volume=302 |pages=1401–1404 |pmid=14631042 |doi=10.1126/science.1089370 |issue=5649 |bibcode=2003Sci...302.1401L |citeseerx=10.1.1.135.974 |s2cid=11246091 }}</ref> However, somewhat paradoxically, species with large population sizes might be so tolerant to the consequences of certain types of errors that they evolve higher error rates, e.g. in [[Transcription (genetics)|transcription]] and [[Translation (biology)|translation]], than small populations.<ref>{{cite journal |last1=Rajon |first1=E. |last2=Masel |first2=J. |author2-link=Joanna Masel |title=Evolution of molecular error rates and the consequences for evolvability |journal=Proceedings of the National Academy of Sciences |date=3 January 2011 |volume=108 |issue=3 |pages=1082–1087 |doi=10.1073/pnas.1012918108 |pmid=21199946 |pmc=3024668|bibcode=2011PNAS..108.1082R |doi-access=free }}</ref>

==See also==
{{Columns-list |colwidth=30em|
* [[Allele frequency spectrum]]
* [[Assortative mating]]
* [[Balancing selection]]
* [[Bias in the introduction of variation]]
* [[Coalescent theory]]
* [[Conservation genetics]]
* [[Constructive neutral evolution]]
* [[Directional selection]]
* [[Mutation#Distribution_of_fitness_effects_(DFE)|Distribution of fitness effects (DFE)]]
* [[Drift-barrier hypothesis]]
* [[Effective population size]]
* [[Error catastrophe]]
* [[Evolutionary landscape]]
* [[Fitness landscape]]
* [[Fixation_(population_genetics)|Fixation]]
* [[Founder effect]]
* [[Gene flow]]
* [[Gene pool]]
* [[Genetic drift]]
* [[Genetic hitchhiking]]
* [[Genetic variation]]
* [[Haldane%27s dilemma]]
* [[Hardy–Weinberg principle|Hardy-Weinberg equilibrium]]
* [[Idealised population]]
* [[Inbreeding]]
* [[Inbreeding depression]]
* [[Infinite sites model]]
* [[Intragenomic conflict]]
* [[Kin selection]]
* [[Linkage disequilibrium]]
* [[McDonald–Kreitman test]]
* [[Meiotic drive]]
* [[Muller%27s ratchet]]
* [[Mutation–selection balance]]
* [[Evolution_of_biological_complexity#Mutational_hazard_hypothesis|Mutational hazard hypothesis]]
* [[Natural selection]]
* [[Neutral theory of molecular evolution]]
* [[Panmixia]]
* [[Outbreeding depression]]
* [[Polymorphism_(biology)|Polymorphism]]
* [[Polygenic adaptation]]
* [[Population size]]
* [[Quantitative genetics]]
* [[Fisherian runaway|Runaway process (Fisherian runaway)]]
* [[Selective sweep]]
* [[Selfish genetic element]]
* [[Sexual selection]]
* [[Shifting balance theory]]
* [[Subfunctionalization]]
* [[Supergene|Supergene (co-adapted gene complex)]]
}}

== References ==
{{Reflist|30em}}

==External links==
{{Commons category}}
* [https://web.archive.org/web/20150123224720/http://www.extension.org/pages/68167/population-development-and-genetics Population Genetics Tutorials] (archived 23 January 2015)
* [http://www.genetics.org/content/205/3/1003 Molecular population genetics]
* [http://alfred.med.yale.edu/alfred/ The ALlele FREquency Database] {{Webarchive|url=https://web.archive.org/web/20110120034110/http://alfred.med.yale.edu/alfred/ |date=2011-01-20 }} at [[Yale University]]
* [https://web.archive.org/web/20090713043812/http://www.ehstrafd.org/ EHSTRAFD.org – Earth Human STR Allele Frequencies Database] (archived 13 July 2009)
* [http://www.esp.org/books/sturt/history/contents/sturt-history-ch-17.pdf History of population genetics]
* [http://www.cosmolearning.com/video-lectures/how-selection-changes-the-genetic-composition-of-population-6688/ How Selection Changes the Genetic Composition of Population], video of lecture by [[Stephen C. Stearns]] ([[Yale University]])
* [[National Geographic Society|National Geographic]]: [https://web.archive.org/web/20060326213734/https://www9.nationalgeographic.com/genographic/atlas.html Atlas of the Human Journey] ([[Haplogroup]]-based human migration maps)

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