The Neutral Theory of Molecular Evolution

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The Neutral Theory of Molecular Evolution
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Author Motoo Kimura

The Neutral Theory of Molecular Evolution is an influential monograph written in 1983 by Japanese evolutionary biologist Motoo Kimura. While the neutral theory of molecular evolution existed since his article in 1968, [1] Kimura felt the need to write a monograph with up-to-date information and evidences showing the importance of his theory in evolution.

Contents

Evolution is a change in the frequency of alleles in a population over time. Mutations occur at random and in the Darwinian evolution model natural selection acts on the genetic variation in a population that has arisen through this mutation. [2] These mutations can be beneficial or deleterious and are selected for or against based on that factor. In this theory, every evolutionary event, mutation, and gene polymorphism (neutral differences in phenotype or genotype) would have to be positively or negatively selected for and show some kind of change over many generations. [3] If these genetic differences grow between different populations speciation events can occur. When this theory was first introduced to the scientific community, there was no understanding of genetic principles such as drift or synonymous mutation.

When molecular biologists, like Motoo Kimura (1979), began to examine the DNA evidence, they found that far more mutations occur in non-protein coding regions or are synonymous mutations in coding regions (which do not change the protein structure or function) and are, therefore, not involved in selection as they do not impact an organism’s fitness. [4] These findings began to show that the positive or negative selection in Darwinian evolution was too simplistic to describe every evolutionary process. [4] Through various experiments Kimura was able to determine that proteins in mammalian lineages were polymorphisms of each other, having only one or two point mutations that did not affect the actions of the protein in any way, whereas in Darwinian evolution a slow pattern of selection in genetic lineages with increasing fitness through generations is expected. [5] The molecular evidence showed that DNA changes more often than what was originally expected and no real pattern was found. Polymorphisms in proteins that have no effect to the function are neutral or nearly neutral and do not get selected for or against at all. [3] This theory would mean that each change in DNA that is passed on to the next generation does not result in a morphological change that can be acted upon by natural selection. [6]

Genetic drift, or the result of a limited population size, can also cause a change in allele frequencies over time that can look like Darwinian evolution while actually being an entirely random or as Kimura puts it "neutral" process. [7] In this scenario a relatively small population can lose neutral alleles through the random deaths or migrations of individuals that have them. It may appear to an onlooker that one trait is being selected for over another but in actuality it is a neutral process that is not necessarily undergoing selection as it would in Darwinian evolution. [8]

Neutral theory in research

Selective constraint in mammalian genes

Within the neutral theory, selective constraint is a type of negative selection that can occur in populations. When selective constraint is reached at a locus negative selection becomes so small that it is effectively neutral. [9] This concept (also brought to prominence by Motoo Kimura (1979) in his expansion of the Neutral Theory of Molecular Evolution (1979) has been put to use in work concerning mammalian genes. [9] In a study done by Price and Graur in 2015, the pair tried to find evidence on whether genes in primates and rodents were either undergoing Darwinian selection or were neutrally evolving under Kimura's model. [10] The number of guanine/cytosine base pairs were utilized in pseudogenes that mimicked nonsynonymous and synonymous mutations that began at what would be expected in a truly neutrally evolving genome for both rodents and primates. Their findings showed that in rodents, the pseudogenes were evolving as one would expect under neutral conditions whereas in primates purifying selection was having an effect on as many as 20% of the pseudogenes tested. [10] By these estimates in primates, 20-40% of their genes could be under selective constraint in the neutral model. [10]

Content

  1. From Lamarck to population genetics
  2. Overdevelopment of the synthetic theory and the proposal of the neutral theory
  3. The neutral mutation-random drift hypothesis as an evolutionary paradigm
  4. Molecular evolutionary rates contrasted with phenotypic evolutionary rates
  5. Some features of molecular evolution
  6. Definition, types and action of natural selection
  7. Molecular structure, selective constraint and the rate of evolution
  8. Population genetics at the molecular level
  9. Summary and conclusion

See also

Related Research Articles

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

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

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

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

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

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

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

The molecular clock is a figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged. The biomolecular data used for such calculations are usually nucleotide sequences for DNA, RNA, or amino acid sequences for proteins. The benchmarks for determining the mutation rate are often fossil or archaeological dates. The molecular clock was first tested in 1962 on the hemoglobin protein variants of various animals, and is commonly used in molecular evolution to estimate times of speciation or radiation. It is sometimes called a gene clock or an evolutionary clock.

<span class="mw-page-title-main">Motoo Kimura</span> Japanese biologist

Motoo Kimura was a Japanese biologist best known for introducing the neutral theory of molecular evolution in 1968. He became one of the most influential theoretical population geneticists. He is remembered in genetics for his innovative use of diffusion equations to calculate the probability of fixation of beneficial, deleterious, or neutral alleles. Combining theoretical population genetics with molecular evolution data, he also developed the neutral theory of molecular evolution in which genetic drift is the main force changing allele frequencies. James F. Crow, himself a renowned population geneticist, considered Kimura to be one of the two greatest evolutionary geneticists, along with Gustave Malécot, after the great trio of the modern synthesis, Ronald Fisher, J. B. S. Haldane, and Sewall Wright.

<span class="mw-page-title-main">Tomoko Ohta</span> Japanese biologist

Tomoko Ohta is a Japanese scientist and Professor Emeritus of the National Institute of Genetics. Ohta works on population genetics/molecular evolution and is known for developing the nearly neutral theory of evolution.

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

Neutral mutations are changes in DNA sequence that are neither beneficial nor detrimental to the ability of an organism to survive and reproduce. In population genetics, mutations in which natural selection does not affect the spread of the mutation in a species are termed neutral mutations. Neutral mutations that are inheritable and not linked to any genes under selection will be lost or will replace all other alleles of the gene. That loss or fixation of the gene proceeds based on random sampling known as genetic drift. A neutral mutation that is in linkage disequilibrium with other alleles that are under selection may proceed to loss or fixation via genetic hitchhiking and/or background selection.

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

Masatoshi Nei was a Japanese-born American evolutionary biologist.

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

The nearly neutral theory of molecular evolution is a modification of the neutral theory of molecular evolution that accounts for the fact that not all mutations are either so deleterious such that they can be ignored, or else neutral. Slightly deleterious mutations are reliably purged only when their selection coefficient are greater than one divided by the effective population size. In larger populations, a higher proportion of mutations exceed this threshold for which genetic drift cannot overpower selection, leading to fewer fixation events and so slower molecular evolution.

The infinite alleles model is a mathematical model for calculating genetic mutations. The Japanese geneticist Motoo Kimura and American geneticist James F. Crow (1964) introduced the infinite alleles model, an attempt to determine for a finite diploid population what proportion of loci would be homozygous. This was, in part, motivated by assertions by other geneticists that more than 50 percent of Drosophila loci were heterozygous, a claim they initially doubted. In order to answer this question they assumed first, that there were a large enough number of alleles so that any mutation would lead to a different allele ; and second, that the mutations would result in a number of different outcomes from neutral to deleterious.

The history of molecular evolution starts in the early 20th century with "comparative biochemistry", but the field of molecular evolution came into its own in the 1960s and 1970s, following the rise of molecular biology. The advent of protein sequencing allowed molecular biologists to create phylogenies based on sequence comparison, and to use the differences between homologous sequences as a molecular clock to estimate the time since the last common ancestor. In the late 1960s, the neutral theory of molecular evolution provided a theoretical basis for the molecular clock, though both the clock and the neutral theory were controversial, since most evolutionary biologists held strongly to panselectionism, with natural selection as the only important cause of evolutionary change. 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.

"Non-Darwinian Evolution" is a scientific paper written by Jack Lester King and Thomas H. Jukes and published in 1969. It is credited, along with Motoo Kimura's 1968 paper "Evolutionary Rate at the Molecular Level", with proposing what became known as the neutral theory of molecular evolution. The paper brings together a wide variety of evidence, ranging from protein sequence comparisons to studies of the Treffers mutator gene in E. coli to analysis of the genetic code to comparative immunology, to argue that most protein evolution is due to neutral mutations and genetic drift. It was published in the journal Science on May 16, 1969.

A nonsynonymous substitution is a nucleotide mutation that alters the amino acid sequence of a protein. Nonsynonymous substitutions differ from synonymous substitutions, which do not alter amino acid sequences and are (sometimes) silent mutations. As nonsynonymous substitutions result in a biological change in the organism, they are subject to natural selection.

A neutral network is a set of genes all related by point mutations that have equivalent function or fitness. Each node represents a gene sequence and each line represents the mutation connecting two sequences. Neutral networks can be thought of as high, flat plateaus in a fitness landscape. During neutral evolution, genes can randomly move through neutral networks and traverse regions of sequence space which may have consequences for robustness and evolvability.

The evolution of bitter taste receptors has been one of the most dynamic evolutionary adaptations to arise in multiple species. This phenomenon has been widely studied in the field of evolutionary biology because of its role in the identification of toxins often found on the leaves of inedible plants. A palate more sensitive to these bitter tastes would, theoretically, have an advantage over members of the population less sensitive to these poisonous substances because they would be much less likely to ingest toxic plants. Bitter-taste genes have been found in a variety of species, and the same genes have been well characterized in several common laboratory animals such as primates and mice, as well as in humans. The primary gene responsible for encoding this ability in humans is the TAS2R gene family which contains 25 functional loci as well as 11 pseudogenes. The development of this gene has been well characterized, with proof that the ability evolved before the human migration out of Africa. The gene continues to evolve in the present day.

The rate of evolution is quantified as the speed of genetic or morphological change in a lineage over a period of time. The speed at which a molecular entity evolves is of considerable interest in evolutionary biology since determining the evolutionary rate is the first step in characterizing its evolution. Calculating rates of evolutionary change is also useful when studying phenotypic changes in phylogenetic comparative biology. In either case, it can be beneficial to consider and compare both genomic data and paleontological data, especially in regards to estimating the timing of divergence events and establishing geological time scales.

References

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  2. Wagner, Andreas (2012). "The Role of Randomness in Darwinian Evolution" (PDF). Philosophy of Science. 79: 95–119. doi:10.1086/663239. S2CID   53475743.
  3. 1 2 Kimura, Motoo (November 1979). "The Neutral Theory of Molecular Evolution". Scientific American. 241 (5): 98–129. Bibcode:1979SciAm.241e..98K. doi:10.1038/scientificamerican1179-98. PMID   504979. S2CID   5119551.
  4. 1 2 Ohta, Tomoko (1992). "The Nearly Neutral Theory of Molecular Evolution". Annual Review of Ecology and Systematics. 23: 263–286. doi:10.1146/annurev.ecolsys.23.1.263.
  5. Suarez, Edna; Barahona, Ana (1996). "The Experimental Roots of the Neutral Theory of Molecular Evolution". History and Philosophy of the Life Sciences. 18: 55–81.
  6. Davies, Vincent (March 2006). "Neutral Theory, Phylogenies, and the Relationship between Phenotypic Change and Evolutionary Rates". Evolution. 60 (3): 476–483. doi:10.1554/04-675.1. JSTOR   4095310. PMID   16637493. S2CID   198154942.
  7. Lynch, Michael; et al. (October 14, 2016). "Genetic drift, selection and the evolution of the mutation rate". Nature Genetics. 17 (11): 704–714. doi:10.1038/nrg.2016.104. PMID   27739533. S2CID   5561271.
  8. Dietrich, Michael R.; Millstein, Roberta L. (2008). "The Role of Causal Processes in the Neutral and Nearly Neutral Theories". Philosophy of Science. 75 (5): 548–559. CiteSeerX   10.1.1.597.5426 . doi:10.1086/594506. S2CID   18736117.
  9. 1 2 Kimura, Motoo (July 1979). "Model of Effectively Neutral Mutations in Which Selective Constraint is Incorporated". Proceedings of the National Academy of Sciences. 76 (7): 3440–3444. Bibcode:1979PNAS...76.3440K. doi: 10.1073/pnas.76.7.3440 . JSTOR   70007. PMC   383841 . PMID   16592684.
  10. 1 2 3 Price, Nicholas; Graur, Dan (November 2015). "Are Synonymous Sites in Primates and Rodents Fully Constrained?". Journal of Molecular Evolution. 82 (1): 51–64. doi:10.1007/s00239-015-9719-3. PMID   26563252. S2CID   15407308.

Further reading