Editing Molecular evolution (section)

==Molecular evolution at one site==

Change at one locus begins with a new [[mutation]], which might become fixed due to some combination of [[natural selection]], [[genetic drift]], and [[gene conversion]].

===Mutation===

{{main|Mutation}}

[[File:Hedgehog with Albinism.jpg|thumb|upright|This hedgehog has no pigmentation due to a mutation.]]

Mutations are permanent, transmissible changes to the [[genetic material]] ([[DNA]] or [[RNA]]) of a [[cell (biology)|cell]] or [[virus]].  Mutations result from errors in [[DNA replication]] during [[cell division]] and by exposure to [[radiation]], chemicals, other environmental stressors, [[virus (biology)|viruses]], or [[transposable elements]]. When [[point mutation]]s to just one base-pair of the DNA fall within a [[Coding region|region coding for a protein]], they are characterized by whether they are [[Synonymous substitution|synonymous]] (do not change the amino acid sequence) or non-synonymous. Other types of mutations modify larger segments of DNA and can cause duplications, insertions, deletions, inversions, and translocations.<ref name="yang2016">Yang, J. (2016, March 23). What are Genetic Mutation? Retrieved from https://www.singerinstruments.com/resource/what-are-genetic-mutation/ .</ref>

The distribution of rates for diverse kinds of mutations is called the "mutation spectrum" (see App. B of <ref name="Stoltzfus2021" />). Mutations of different types occur at widely varying rates. Point mutation rates for most organisms are very low, roughly 10<sup>−9</sup> to 10<sup>−8</sup> per site per generation,<ref>{{cite journal |last1=Wang |first1=Yiguan |last2=Obbard |first2=Darren J |title=Experimental estimates of germline mutation rate in eukaryotes: a phylogenetic meta-analysis |journal=Evolution Letters |date=19 July 2023 |volume=7 |issue=4 |pages=216–226 |doi=10.1093/evlett/qrad027|pmid=37475753 |pmc=10355183 |hdl=20.500.11820/8ffd5b76-77ae-4764-ae31-de2fb8aa35cf |hdl-access=free }}</ref> though some viruses have higher mutation rates on the order of 10<sup>−6</sup> per site per generation.<ref>{{cite journal |last1=Peck |first1=Kayla M. |last2=Lauring |first2=Adam S. |title=Complexities of Viral Mutation Rates |journal=Journal of Virology |date=15 July 2018 |volume=92 |issue=14 |pages=e01031-17 |doi=10.1128/JVI.01031-17|pmid=29720522 |pmc=6026756 }}</ref> [[Transition (genetics)|Transitions]] (A ↔ G or C ↔ T) are more common than [[transversion]]s ([[purine]] (adenine or guanine)) ↔ [[pyrimidine]] (cytosine or thymine, or in RNA, uracil)).<ref>{{Cite web | url=https://www.mun.ca/biology/scarr/Transitions_vs_Transversions.html | title=Transitions vs transversions}}</ref> Perhaps the most common type of mutation in humans is a change in the length of a [[short tandem repeat]] (e.g., the CAG repeats underlying various disease-associated mutations). Such STR mutations may occur at rates on the order of 10<sup>−3</sup> per generation.<ref name=WeberWong1993>{{cite journal | author=J. L. Weber and C. Wong | year=1993 | title=Mutation of human short tandem repeats | journal=Hum Mol Genet | volume=2 | issue=8 | pages=1123–8 | doi=10.1093/hmg/2.8.1123 | pmid=8401493 }}</ref>

Different frequencies of different types of mutations can play an important role in evolution via [[bias in the introduction of variation]] (arrival bias), contributing to parallelism, trends, and differences in the navigability of adaptive landscapes.<ref name=CanoPayne2020>{{cite journal | author=A. V. Cano and J. L. Payne | year=2020 | title=Mutation bias interacts with composition bias to influence adaptive evolution | journal=PLOS Computational Biology | volume=16 | issue=9 | pages=e1008296 | doi=10.1371/journal.pcbi.1008296 | pmid=32986712 | pmc=7571706 | bibcode=2020PLSCB..16E8296C | doi-access=free }}</ref><ref name=Nei2013>{{cite book | author=M. Nei | year=2013 | title=Mutation-Driven Evolution | publisher=Oxford University Press }}</ref> Mutation bias makes systematic or predictable contributions to [[parallel evolution]].<ref name=Stoltzfus2021>{{cite book | author=A. Stoltzfus | year=2021 | title=Mutation, Randomness and Evolution | publisher=Oxford, Oxford }}</ref> Since the 1960s, genomic [[GC content]] has been thought to reflect mutational tendencies.<ref name=Freese1962>{{cite journal | author=E. Freese | year=1962 | title=On the Evolution of the Base Composition of DNA | journal=J. Theor. Biol. | volume=3 | issue=1 | pages=82–101 | doi=10.1016/S0022-5193(62)80005-8 | bibcode=1962JThBi...3...82F | quote = "It is unimportant in this connection whether selection has been negligible or self-cancelling." }}</ref><ref name=Sueoka1962>{{cite journal | author=N. Sueoka | year=1962 | title=On the Genetic Basis of Variation and Heterogeneity of DNA Base Composition | journal=Proc. Natl. Acad. Sci. U.S.A. | volume=48 | issue=4 | pages=582–592 | doi=10.1073/pnas.48.4.582
| pmid=13918161 | pmc=220819 | bibcode=1962PNAS...48..582S | doi-access=free }}</ref> Mutational biases also contribute to [[codon usage bias]].<ref name=StoltzfusYampolsky2009>{{cite journal | author=A. Stoltzfus and L. Y. Yampolsky | year=2009 | title=Climbing mount probable: mutation as a cause of nonrandomness in evolution | journal=J Hered | volume=100 | issue=5 | pages=637–47 | doi=10.1093/jhered/esp048 | pmid=19625453 | doi-access=free }}</ref> Although such hypotheses are often associated with neutrality, recent theoretical and empirical results have established that mutational tendencies can influence both neutral and adaptive evolution via [[bias in the introduction of variation]] (arrival bias).

===Selection===

{{Main|Natural selection}}

Selection can occur when an allele confers greater [[fitness (biology)|fitness]], i.e. greater ability to survive or reproduce, on the average individual than carries it. A '''selectionist''' approach emphasizes e.g. that biases in [[codon usage bias|codon usage]] are due at least in part to the ability of even [[weak selection]] to shape molecular evolution.<ref>{{cite journal | vauthors = Hershberg R, Petrov DA | title = Selection on codon bias | journal = Annual Review of Genetics | volume = 42 | issue = 1 | pages = 287–299 | date = December 2008 | pmid = 18983258 | doi = 10.1146/annurev.genet.42.110807.091442 | s2cid = 7085012 }}</ref>

Selection can also operate at the gene level at the expense of organismal fitness, resulting in [[intragenomic conflict]]. This is because there can be a selective advantage for [[Selfish DNA|selfish genetic elements]] in spite of a host cost. Examples of such selfish elements include [[transposable elements]], [[meiotic drive]]rs, and [[Selfish genetic element#Selfish mitochondria|selfish mitochondria]].

Selection can be [[Population genetics#Detecting selection|detected]] using the [[Ka/Ks ratio]], the [[McDonald–Kreitman test]]. Rapid [[Adaptation|adaptive evolution]] is often found for genes involved in [[intragenomic conflict]], [[sexual antagonistic coevolution]], and the [[immune system]].

===Genetic drift===

{{Main|Genetic drift}}

Genetic drift is the change of allele frequencies from one generation to the next due to stochastic effects of [[random sampling]] in finite populations. These effects can accumulate until a mutation becomes [[Fixation (population genetics)|fixed]]  in a [[population]]. For neutral mutations, the rate of fixation per generation is equal to the mutation rate per replication. A relatively constant mutation rate thus produces a constant rate of change per generation (molecular clock).

Slightly deleterious mutations with a [[selection coefficient]] less than a threshold value of 1 / the [[effective population size]] can also fix. Many genomic features have been ascribed to accumulation of nearly neutral detrimental mutations as a result of small effective population sizes.<ref>{{cite book | vauthors = Lynch M |year=2007|title= The Origins of Genome Architecture |publisher=Sinauer|isbn=978-0-87893-484-3|author-link=Michael Lynch (geneticist)}}</ref> With a smaller effective population size, a larger variety of mutations will behave as if they are neutral due to inefficiency of selection.

===Gene conversion===

{{Main|Gene conversion}}

Gene conversion occurs during recombination, when nucleotide damage is [[DNA repair|repaired]] using  an homologous genomic region as a template. It can be a biased process, i.e. one allele may have a higher probability of being the donor than the other in a gene conversion event. In particular, GC-biased gene conversion tends to increase the [[GC-content]] of genomes, particularly in regions with higher recombination rates.<ref name="Duret_2009">{{cite journal | vauthors = Duret L, Galtier N | title = Biased gene conversion and the evolution of mammalian genomic landscapes | journal = Annual Review of Genomics and Human Genetics | volume = 10 | pages = 285–311 | year = 2009 | pmid = 19630562 | doi = 10.1146/annurev-genom-082908-150001 }}</ref> There is also evidence for GC bias in the mismatch repair process.<ref name="Galtier_2001">{{cite journal | vauthors = Galtier N, Piganeau G, Mouchiroud D, Duret L | title = GC-content evolution in mammalian genomes: the biased gene conversion hypothesis | journal = Genetics | volume = 159 | issue = 2 | pages = 907–911 | date = October 2001 | pmid = 11693127 | pmc = 1461818 | doi = 10.1093/genetics/159.2.907 }}</ref> It is thought that this may be an adaptation to the high rate of methyl-cytosine deamination which can lead to C→T transitions.

The dynamics of biased gene conversion resemble those of natural selection, in that a favored allele will tend to increase [[Exponential growth|exponentially]] in frequency when rare.