Editing Molecular evolution

{{Short description|Process of change in the sequence composition of cellular molecules across generations}}
{{Evolutionary biology}}
'''Molecular evolution''' describes how [[Heredity|inherited]] [[DNA]] and/or [[RNA]] change over [[evolution]]ary time, and the consequences of this for [[protein]]s and other components of [[Cell (biology)|cells]] and [[organism]]s. Molecular evolution is the basis of [[phylogenetics|phylogenetic]] approaches to describing the [[Tree of life (biology)|tree of life]]. Molecular evolution overlaps with [[population genetics]], especially on shorter timescales. Topics in molecular evolution include the origins of new genes, the genetic nature of [[complex traits]], the genetic basis of [[adaptation]] and [[speciation]], the [[Evolutionary developmental biology|evolution of development]], and patterns and processes underlying [[genome|genomic]] changes during evolution.

==History==
{{Main|History of molecular evolution}}

The [[history of molecular evolution]] starts in the early 20th century with comparative [[biochemistry]], and the use of "fingerprinting" methods such as immune assays, [[gel electrophoresis]], and [[paper chromatography]] in the 1950s to explore [[homologous protein]]s.<ref name=Dietrich>{{cite journal | vauthors = Dietrich MR |title = Paradox and persuasion: negotiating the place of molecular evolution within evolutionary biology|journal = Journal of the History of Biology|volume=31|issue = 1 | pages=85–111|year=1998|pmid=11619919|doi= 10.1023/A:1004257523100|s2cid=29935487 }}</ref><ref name=Hagen>{{cite journal | vauthors = Hagen JB | title = Naturalists, molecular biologists, and the challenges of molecular evolution | journal = Journal of the History of Biology|volume=32|issue=2|pages=321–341|year=1999|pmid = 11624208 | doi = 10.1023/A:1004660202226 | s2cid = 26994015 }}</ref> The advent of [[protein sequencing]] allowed molecular biologists to create phylogenies based on sequence comparison, and to use the differences between [[Sequence homology|homologous sequences]] as a [[molecular clock]] to estimate the time since the [[most recent common ancestor]].<ref>{{cite journal |last1=Zuckerkandl |first1=Emile |last2=Pauling |first2=Linus |title=Molecules as documents of evolutionary history |journal=Journal of Theoretical Biology |date=March 1965 |volume=8 |issue=2 |pages=357–366 |doi=10.1016/0022-5193(65)90083-4|pmid=5876245 |bibcode=1965JThBi...8..357Z }}</ref><ref name=Dietrich/> The surprisingly large amount of molecular divergence within and between species inspired the [[neutral theory of molecular evolution]] in the late 1960s.<ref name=Kimura68>{{cite journal | vauthors = Kimura M | title = Evolutionary rate at the molecular level | journal = Nature | volume = 217 | issue = 5129 | pages = 624–626 | date = February 1968 | pmid = 5637732 | doi = 10.1038/217624a0 | s2cid = 4161261 | bibcode = 1968Natur.217..624K }}</ref><ref name=King>{{cite journal | vauthors = King JL, Jukes TH | title = Non-Darwinian evolution | journal = Science | volume = 164 | issue = 3881 | pages = 788–798 | date = May 1969 | pmid = 5767777 | doi = 10.1126/science.164.3881.788 | bibcode = 1969Sci...164..788L }}</ref><ref name=Kim83>{{cite book |author=Kimura, M. |year=1983 |title=The Neutral Theory of Molecular Evolution|publisher=[[Cambridge University Press]], Cambridge| isbn=0-521-23109-4|author-link=Motoo Kimura }}</ref> Neutral theory also provided a theoretical basis for the [[molecular clock]], although this is not needed for the clock's validity. After the 1970s, nucleic acid sequencing allowed molecular evolution to reach beyond proteins to highly conserved [[ribosomal RNA]] sequences, the foundation of a reconceptualization of the early [[history of life]].<ref name=Dietrich/> The [[Society for Molecular Biology and Evolution]] was founded in 1982.

==Molecular phylogenetics==
{{Main|Molecular systematics|Phylogenetics}}

[[File:Site pattern frequencies models.jpg|thumb|440x440px|[[Multiple sequence alignment]] (in this case DNA sequences) and illustrations of the use of substitution models to make evolutionary inferences. The data in this alignment (in this case a toy example with 18 sites) is converted to a set of site patterns. The site patterns are shown along with the number of times they occur in alignment. These site patterns are used to calculate the [[Likelihood function|likelihood]] given the substitution model and a [[phylogenetic tree]] (in this case an unrooted four-taxon tree). It is also necessary to assume a substitution model to estimate evolutionary distances for pairs of sequences (distances are the number of substitutions that have occurred since sequences had a common ancestor). The evolutionary distance equation (''d''<sub>12</sub>) is based on the simple model proposed by [[Thomas H. Jukes|Jukes]] and [[Charles Cantor|Cantor]] in 1969. The equation transforms the proportion of nucleotide differences between taxa 1 and 2 (''p''<sub>12</sub> = 4/18; the four site patterns that differ between taxa 1 and 2 are indicated with asterisks) into an evolutionary distance (in this case ''d''<sub>12</sub>=0.2635 substitutions per site). ]]

Molecular phylogenetics uses [[DNA]], [[RNA]], or [[protein]] sequences to resolve questions in [[systematics]], i.e. about their correct [[Taxonomy (biology)|scientific classification]] from the point of view of [[History of life|evolutionary history]]. The result of a molecular [[phylogenetics|phylogenetic]] analysis is expressed in a [[phylogenetic tree]]. Phylogenetic inference is conducted using data from [[DNA sequencing]]. This is [[Multiple sequence alignment|aligned]] to identify which sites are [[Homology (biology)|homologous]]. A [[substitution model]] describes what patterns are expected to be common or rare. Sophisticated [[Computational phylogenetics|computational inference]] is then used to generate one or more plausible trees.

Some phylogenetic methods account for variation among sites and [[Heterotachy|among tree branches]]. Different genes, e.g. [[hemoglobin]] vs. [[cytochrome c]], generally evolve at different [[Rate of evolution|rates]].<ref name="Fay">{{cite journal | vauthors = Fay JC, Wu CI | title = Sequence divergence, functional constraint, and selection in protein evolution | journal = Annual Review of Genomics and Human Genetics | volume = 4 | pages = 213–235 | date = 2003 | pmid = 14527302 | doi = 10.1146/annurev.genom.4.020303.162528 | s2cid = 6360375 | doi-access = free }}</ref> These rates are relatively constant over time (e.g., hemoglobin does not evolve at the same rate as cytochrome c, but hemoglobins from humans, mice, etc. do have comparable rates of evolution), although rapid evolution along one branch can indicate increased [[directional selection]] on that branch.<ref>{{cite journal |last1=Álvarez-Carretero |first1=Sandra |last2=Kapli |first2=Paschalia |last3=Yang |first3=Ziheng |title=Beginner's Guide on the Use of PAML to Detect Positive Selection |journal=Molecular Biology and Evolution |date=4 April 2023 |volume=40 |issue=4 |doi=10.1093/molbev/msad041|pmid=37096789 |pmc=10127084 }}</ref> [[Purifying selection]] causes functionally important regions to evolve more slowly, and amino acid substitutions involving [[Conservative replacement|similar amino acids]] occurs more often than dissimilar substitutions.<ref name="Fay" />

[[File:Five Stages of Molecular Phylogenetic Analysis.png|800x80px|center|thumb|Five Stages of Molecular Phylogenetic Analysis]]

==Gene family evolution==
{{main|Gene family}}

[[File:Ortholog paralog analog examples.svg|thumb|400x400px|Gene [[Phylogenetic tree|phylogeny]] as lines within grey species phylogeny. Top: An ancestral [[gene duplication]] produces two paralogs ([[histone H1.1]] and [[Histone H1.2|1.2]]). A speciation event produces orthologs in the two daughter species (human and chimpanzee). Bottom: in a separate species ([[E. coli]]), a gene has a similar function ([[histone-like nucleoid-structuring protein]]) but has a separate evolutionary origin and so is an [[Analogy (biology)|analog]].]]

[[Gene duplication]] can produce multiple [[Sequence homology|homologous]] proteins (paralogs) within the same species. [[Phylogenetics|Phylogenetic]] analysis of proteins has revealed how proteins evolve and change their structure and function over time.<ref name="2017-Hanukoglu-b">{{cite journal | vauthors = Hanukoglu I | title = ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters | journal = The FEBS Journal | volume = 284 | issue = 4 | pages = 525–545 | date = February 2017 | pmid = 27580245 | doi = 10.1111/febs.13840 | s2cid = 24402104 | url = https://zenodo.org/record/890906 }}</ref><ref name="2016-Hanukoglu">{{cite journal | vauthors = Hanukoglu I, Hanukoglu A | title = Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases | journal = Gene | volume = 579 | issue = 2 | pages = 95–132 | date = April 2016 | pmid = 26772908 | pmc = 4756657 | doi = 10.1016/j.gene.2015.12.061 }}</ref>

For example, [[ribonucleotide reductase]] (RNR) has evolved a multitude of structural and functional variants. '''Class I''' RNRs use a [[ferritin]] subunit and differ by the metal they use as cofactors. In '''class II''' RNRs, the [[thiyl radical]] is generated using an [[adenosylcobalamin]] cofactor and these enzymes do not require additional subunits (as opposed to class I which do). In '''class III''' RNRs, the thiyl radical is generated using [[S-Adenosyl methionine|S-adenosylmethionine]] bound to a [<nowiki/>[[Iron-sulfur protein|4Fe-4S]]] cluster. That is, within a single family of proteins numerous structural and functional mechanisms can evolve.<ref>{{cite journal | vauthors = Burnim AA, Spence MA, Xu D, Jackson CJ, Ando N | title = Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade | journal = eLife | volume = 11 | pages = e79790 | date = September 2022 | pmid = 36047668|pmc=9531940|doi = 10.7554/eLife.79790 | veditors = Ben-Tal N, Weigel D, Ben-Tal N, Stubbe J, Hofer A | doi-access = free }}</ref>

In a proof-of-concept study, Bhattacharya and colleagues converted [[myoglobin]], a non-enzymatic oxygen storage protein, into a highly efficient [[Benzisoxazole|Kemp eliminase]] using only three [[mutation]]s. This demonstrates that only few mutations are needed to radically change the function of a protein.<ref>{{cite journal | vauthors = Bhattacharya S, Margheritis EG, Takahashi K, Kulesha A, D'Souza A, Kim I, Yoon JH, Tame JR, Volkov AN, Makhlynets OV, Korendovych IV | display-authors = 6 | title = NMR-guided directed evolution | journal = Nature | volume = 610 | issue = 7931 | pages = 389–393 | date = October 2022 | pmid = 36198791 | doi = 10.1038/s41586-022-05278-9 | pmc = 10116341 | bibcode = 2022Natur.610..389B | s2cid = 245067145 }}</ref> [[Directed evolution]] is the attempt to engineer proteins using methods inspired by molecular evolution.

==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.

==Genome architecture==
{{Main|Genome evolution}}

===Genome size===
{{Main|Genome size}}
Genome size is influenced by the amount of repetitive DNA as well as number of genes in an organism.  Some organisms, such as most bacteria, ''Drosophila'', and ''Arabidopsis'' have particularly compact genomes with little repetitive content or non-coding DNA.  Other organisms, like mammals or maize, have large amounts of repetitive DNA, long [[introns]], and substantial spacing between genes. The [[C-value paradox]]  refers to the lack of correlation between organism 'complexity' and genome size.  Explanations for the so-called paradox are two-fold.  First, repetitive genetic elements can comprise large portions of the genome for many organisms, thereby inflating DNA content of the haploid genome. Repetitive genetic elements are often descended from [[transposable elements]].

Secondly, the number of genes is not necessarily indicative of the number of developmental stages or tissue types in an organism.  An organism with few developmental stages or tissue types may have large numbers of genes that influence non-developmental phenotypes, inflating gene content relative to developmental gene families.

Neutral explanations for genome size suggest that when population sizes are small, many mutations become nearly neutral.  Hence, in small populations repetitive content and other [[junk DNA|'junk' DNA]] can accumulate without placing the organism at a competitive disadvantage.  There is little evidence to suggest that genome size is under strong widespread selection in multicellular eukaryotes.  Genome size, independent of gene content, correlates poorly with most physiological traits and many eukaryotes, including mammals, harbor very large amounts of repetitive DNA.

However, [[birds]] likely have experienced strong selection for reduced genome size, in response to changing energetic needs for flight.  Birds, unlike humans, produce nucleated red blood cells, and larger nuclei lead to lower levels of oxygen transport.  Bird metabolism is far higher than that of mammals, due largely to flight, and oxygen needs are high.  Hence, most birds have small, compact genomes with few repetitive elements.  Indirect evidence suggests that non-avian theropod dinosaur ancestors of modern birds<ref>{{cite journal | vauthors = Organ CL, Shedlock AM, Meade A, Pagel M, Edwards SV | title = Origin of avian genome size and structure in non-avian dinosaurs | journal = Nature | volume = 446 | issue = 7132 | pages = 180–184 | date = March 2007 | pmid = 17344851 | doi = 10.1038/nature05621 | s2cid = 3031794 | bibcode = 2007Natur.446..180O }}</ref> also had reduced genome sizes, consistent with endothermy and high energetic needs for running speed.  Many bacteria have also experienced selection for small genome size, as time of replication and energy consumption are so tightly correlated with fitness.

===Chromosome number and organization===
The ant ''Myrmecia pilosula'' has only a single pair of chromosomes<ref name=Crosland>{{cite journal | vauthors = Crosland MW, Crozier RH | title = Myrmecia pilosula, an Ant with Only One Pair of Chromosomes | journal = Science | volume = 231 | issue = 4743 | pages = 1278 | date = March 1986 | pmid = 17839565 | doi = 10.1126/science.231.4743.1278 | s2cid = 25465053 | bibcode = 1986Sci...231.1278C }}</ref> whereas the Adders-tongue fern  ''[[Ophioglossum]] reticulatum'' has up to 1260 chromosomes.<ref name="Grubben2004">{{cite book|author=Gerardus J. H. Grubben|title=Vegetables|url=https://archive.org/details/bub_gb_6jrlyOPfr24C|access-date=10 March 2013|year=2004|publisher=PROTA|isbn=978-90-5782-147-9|page=[https://archive.org/details/bub_gb_6jrlyOPfr24C/page/n404 404]}}</ref> The  [[List of organisms by chromosome count|number of chromosomes]] in an organism's genome does not necessarily correlate with the amount of DNA in its genome. The genome-wide amount of [[Genetic recombination|recombination]] is directly controlled by the number of chromosomes, with one [[Chromosomal crossover|crossover]] per chromosome or per chromosome arm, depending on the species.<ref>{{cite journal |last1=Pardo-Manuel de Villena |first1=Fernando |last2=Sapienza |first2=Carmen |title=Recombination is proportional to the number of chromosome arms in mammals |journal=Mammalian Genome |date=April 2001 |volume=12 |issue=4 |pages=318–322 |doi=10.1007/s003350020005|pmid=11309665 }}</ref>

Changes in chromosome number can play a key role in [[speciation]], as differing chromosome numbers can serve as a [[Reproductive isolation|barrier to reproduction]] in hybrids.  Human [[chromosome 2]] was created from a fusion of two chimpanzee chromosomes and still contains central [[telomeres]] as well as a vestigial second [[centromere]].  [[Polyploidy]], especially allopolyploidy, which occurs often in plants, can also result in reproductive incompatibilities with parental species.  ''Agrodiatus'' blue butterflies have diverse chromosome numbers ranging from n=10 to n=134 and additionally have one of the highest rates of speciation identified to date.<ref name="Butterflies">{{cite journal | vauthors = Kandul NP, Lukhtanov VA, Pierce NE | title = Karyotypic diversity and speciation in Agrodiaetus butterflies | journal = Evolution; International Journal of Organic Evolution | volume = 61 | issue = 3 | pages = 546–559 | date = March 2007 | pmid = 17348919 | doi = 10.1111/j.1558-5646.2007.00046.x | doi-access = free }}</ref>

[[Cilliate]] genomes house each gene in individual chromosomes.

===Organelles===
{{Main|Organelle}}
[[File:Animal cells SwissBioPics DL20221120.svg|thumb|150x150px|Animal cell showing organelles.]]
In addition to the [[Nuclear DNA|nuclear genome]], endosymbiont organelles contain their own genetic material. [[Mitochondrion|Mitochondrial]] and [[chloroplast]] DNA varies across taxa, but [[Membrane-bound protein (disambiguation)|membrane-bound protein]]s, especially [[electron transport chain]] constituents are most often encoded in the organelle.  Chloroplasts and [[Mitochondrion|mitochondria]] are maternally inherited in most species, as the organelles must pass through the [[Egg cell|egg]].  In a rare departure, some species of [[mussel]]s are known to inherit mitochondria from father to son.

==Origins of new genes==

New [[gene]]s arise from several different genetic mechanisms including [[gene duplication]], [[de novo gene birth|''de novo'' gene birth]], [[Gene duplication#Retrotransposition|retrotransposition]], [[chimeric gene]] formation, recruitment of non-coding sequence into an existing gene, and gene truncation.

[[Gene duplication]] initially leads to redundancy. However, duplicated gene sequences can mutate to develop [[Neofunctionalization|new functions]] or [[Subfunctionalization|specialize]] so that the new gene performs a subset of the original ancestral functions. [[Retrotransposition]] duplicates genes by copying [[mRNA]] to DNA and inserting it into the genome.  Retrogenes generally insert into new genomic locations, lack [[intron]]s, and sometimes develop new expression patterns and functions.

[[Chimeric gene]]s form when duplication, deletion, or incomplete retrotransposition combines portions of two different coding sequences to produce a novel gene sequence.  Chimeras often cause regulatory changes and can shuffle protein domains to produce novel adaptive functions.

[[De novo gene birth|''De novo'' gene birth]] can give rise to protein-coding genes and non-coding genes from previously non-functional DNA.<ref>{{cite journal | vauthors = McLysaght A, Guerzoni D | title = New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 370 | issue = 1678 | pages = 20140332 | date = September 2015 | pmid = 26323763 | pmc = 4571571 | doi = 10.1098/rstb.2014.0332 }}</ref>  For instance, Levine and colleagues reported the origin of five new genes in the ''D. melanogaster'' genome.<ref name="j3" /><ref name="j4" /> Similar ''de novo'' origin of genes has also been shown in other organisms such as yeast,<ref name="j5" /> rice<ref name="j6" /> and humans.<ref name="j7" /> ''De novo'' genes may evolve from spurious transcripts that are already expressed at low levels.<ref>{{cite journal | vauthors = Wilson BA, Masel J | title = Putatively noncoding transcripts show extensive association with ribosomes | journal = Genome Biology and Evolution | volume = 3 | pages = 1245–1252 | year = 2011 | pmid = 21948395 | pmc = 3209793 | doi = 10.1093/gbe/evr099 }}</ref>

==Constructive neutral evolution==
{{Main|Constructive neutral evolution}}

[[Constructive neutral evolution]] (CNE) explains that complex systems can emerge and spread into a population through neutral transitions with the principles of excess capacity, presuppression, and ratcheting,<ref>{{cite journal | vauthors = Stoltzfus A | title = On the possibility of constructive neutral evolution | journal = Journal of Molecular Evolution | volume = 49 | issue = 2 | pages = 169–181 | date = August 1999 | pmid = 10441669 | doi = 10.1007/PL00006540 | bibcode = 1999JMolE..49..169S | s2cid = 1743092 }}</ref><ref>{{cite journal | vauthors = Stoltzfus A | title = Constructive neutral evolution: exploring evolutionary theory's curious disconnect | journal = Biology Direct | volume = 7 | issue = 1 | pages = 35 | date = October 2012 | pmid = 23062217 | pmc = 3534586 | doi = 10.1186/1745-6150-7-35 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Muñoz-Gómez SA, Bilolikar G, Wideman JG, Geiler-Samerotte K | title = Constructive Neutral Evolution 20 Years Later | journal = Journal of Molecular Evolution | volume = 89 | issue = 3 | pages = 172–182 | date = April 2021 | pmid = 33604782 | pmc = 7982386 | doi = 10.1007/s00239-021-09996-y | bibcode = 2021JMolE..89..172M }}</ref> and it has been applied in areas ranging from the origins of the [[spliceosome]] to the complex interdependence of [[Microbial consortium|microbial communities]].<ref>{{cite journal | vauthors = Lukeš J, Archibald JM, Keeling PJ, Doolittle WF, Gray MW | title = How a neutral evolutionary ratchet can build cellular complexity | journal = IUBMB Life | volume = 63 | issue = 7 | pages = 528–537 | date = July 2011 | pmid = 21698757 | doi = 10.1002/iub.489 | s2cid = 7306575 }}</ref><ref>{{cite journal | vauthors = Vosseberg J, Snel B | title = Domestication of self-splicing introns during eukaryogenesis: the rise of the complex spliceosomal machinery | journal = Biology Direct | volume = 12 | issue = 1 | pages = 30 | date = December 2017 | pmid = 29191215 | pmc = 5709842 | doi = 10.1186/s13062-017-0201-6 | doi-access = free }}</ref><ref>{{Cite journal | vauthors = Brunet TD, Doolittle WF |date=19 March 2018 |title=The generality of Constructive Neutral Evolution |journal=Biology & Philosophy |language=en |volume=33 |issue=1 |pages=2 |doi=10.1007/s10539-018-9614-6 |issn=1572-8404 |s2cid=90290787|url=https://www.repository.cam.ac.uk/handle/1810/278897 |url-access=subscription }}</ref>

==Journals and societies==
The Society for Molecular Biology and Evolution publishes the journals "Molecular Biology and Evolution" and "Genome Biology and Evolution" and holds an annual international meeting. Other journals dedicated to molecular evolution include ''Journal of Molecular Evolution'' and ''Molecular Phylogenetics and Evolution''. Research in molecular evolution is also published in journals of [[genetics]], [[molecular biology]], [[genomics]], [[systematics]], and [[evolutionary biology]].

== See also ==
{{Portal|Evolutionary biology|Biology}}
{{div col|colwidth=22em}}
* [[Evolution]]
* [[E. coli long-term evolution experiment|''E. coli'' long-term evolution experiment]]
* [[Evolutionary physiology]]
* [[Genomic organization]]
* [[Genome evolution]]
* [[Heterotachy]]
* [[History of molecular evolution]]
* [[Horizontal gene transfer]]
* [[Human evolution]]
* [[Molecular clock]]
* [[Molecular paleontology]]
* [[Nearly neutral theory of molecular evolution]]
* [[Neutral theory of molecular evolution]]
* [[Nucleotide diversity]]
* [[Phylogenetic comparative methods]]
* [[Phylogenetics]]
* [[Population genetics]]
* [[Selection (biology)|Selection]]
{{div col end}}

== References ==
{{Reflist|35em|refs=
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<ref name=j1>{{cite journal | vauthors = Suárez-Díaz E, Anaya-Muñoz VH | title = History, objectivity, and the construction of molecular phylogenies | journal = Studies in History and Philosophy of Biological and Biomedical Sciences | volume = 39 | issue = 4 | pages = 451–468 | date = December 2008 | pmid = 19026976 | doi = 10.1016/j.shpsc.2008.09.002 | name-list-style = amp }}</ref>

<ref name=j2>{{cite journal| vauthors = Ahlquist JE |year= 1999|title= Charles G. Sibley: A commentary on 30 years of collaboration|journal=The Auk|volume=116|issue= 3|url=http://sora.unm.edu/node/26122|pages= 856–860|doi=10.2307/4089352}}</ref>-->

<ref name=j3>{{cite journal | vauthors = Levine MT, Jones CD, Kern AD, Lindfors HA, Begun DJ | title = Novel genes derived from noncoding DNA in Drosophila melanogaster are frequently X-linked and exhibit testis-biased expression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 26 | pages = 9935–9939 | date = June 2006 | pmid = 16777968 | pmc = 1502557 | doi = 10.1073/pnas.0509809103 | doi-access = free | bibcode = 2006PNAS..103.9935L }}</ref>

<ref name=j4>{{cite journal | vauthors = Zhou Q, Zhang G, Zhang Y, Xu S, Zhao R, Zhan Z, Li X, Ding Y, Yang S, Wang W | display-authors = 6 | title = On the origin of new genes in Drosophila | journal = Genome Research | volume = 18 | issue = 9 | pages = 1446–1455 | date = September 2008 | pmid = 18550802 | pmc = 2527705 | doi = 10.1101/gr.076588.108 }}</ref>

<ref name=j5>{{cite journal | vauthors = Cai J, Zhao R, Jiang H, Wang W | title = De novo origination of a new protein-coding gene in Saccharomyces cerevisiae | journal = Genetics | volume = 179 | issue = 1 | pages = 487–496 | date = May 2008 | pmid = 18493065 | pmc = 2390625 | doi = 10.1534/genetics.107.084491 }}</ref>

<ref name=j6>{{cite journal | vauthors = Xiao W, Liu H, Li Y, Li X, Xu C, Long M, Wang S | title = A rice gene of de novo origin negatively regulates pathogen-induced defense response | journal = PLOS ONE | volume = 4 | issue = 2 | pages = e4603 | year = 2009 | pmid = 19240804 | pmc = 2643483 | doi = 10.1371/journal.pone.0004603 | veditors = El-Shemy HA | doi-access = free | bibcode = 2009PLoSO...4.4603X }}</ref>

<ref name=j7>{{cite journal | vauthors = Knowles DG, McLysaght A | title = Recent de novo origin of human protein-coding genes | journal = Genome Research | volume = 19 | issue = 10 | pages = 1752–1759 | date = October 2009 | pmid = 19726446 | pmc = 2765279 | doi = 10.1101/gr.095026.109 }}</ref>
}}

== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Li WH |author-link=Wen-Hsiung Li |year=2006 |title= Molecular Evolution |publisher=Sinauer|isbn=0-87893-480-4 }}
* {{cite book | vauthors = Lynch M |author-link=Michael Lynch (geneticist) |year=2007|title= The Origins of Genome Architecture |publisher=Sinauer|isbn=978-0-87893-484-3}}
* {{cite book | veditors = Meyer A, van de Peer Y |title=Genome evolution : gene and genome duplications and the origin of novel gene functions |date=2003 |publisher=Kluwer Academic Pub |location=Dordrecht |isbn=978-1-4020-1021-7}}
* {{cite book | vauthors = Gregory TR |title=The evolution of the genome |date=2005 |publisher=Elsevier Academic |location=Burlington, MA |isbn=978-0-12-301463-4}}
* {{cite book | vauthors = Levinson G |title=Rethinking evolution : the revolution that's hiding in plain sight |date=2020 |location=London | publisher = World Scientific |isbn=978-1-78634-726-8}}
* {{cite book |name-list-style=vanc | last1 = Graur |first1 = D |author-link1=Dan Graur |last2=Li |first2=WH |author-link2=Wen-Hsiung Li |year=2000 |title=Fundamentals of molecular evolution |publisher=Sinauer |isbn=0-87893-266-6}}
* {{cite book | vauthors = Graur D |author-link=Dan Graur |title=Molecular and genome evolution |date=2016 |publisher=Sinauer associates, Inc |location=Sunderland (Mass.) |isbn=978-1605354699}}
{{refend}}

{{Evolution}}
{{Authority control}}

Category: molecular
evolution (kimura 1968)

[[Category:Molecular evolution| ]]