Nearly neutral theory of molecular evolution
Encyclopedia
The nearly neutral theory of molecular evolution is a modification of the neutral theory of molecular evolution
that accounts for slightly advantageous or deleterious mutation
s at the molecular level. The nearly neutral theory was proposed by Tomoko Ohta
in 1973 (including only deleterious mutations) and expanded in the early 1990s to include both advantageous and deleterious nearly neutral mutations. Unlike in Motoo Kimura
's original neutral theory—which dealt only with mutations unaffected by natural selection
—the nearly neutral theory predicts a relationship between population size
and the rate of molecular evolution
: in larger populations, genetic drift
, which can bring even slightly deleterious mutations to fixation
, is a weaker force, so evolution happens more slowly than in smaller populations .
evolution (the "molecular clock
") are fairly independent of generation time, while rates of noncoding DNA
divergence are inversely proportional to generation time. Noting that population size is generally inversely proportional to generation time, Tomoko Ohta proposed that most amino acid
substitutions are slightly deleterious while noncoding DNA substitutions are more neutral. In this case, the faster rate of neutral evolution in proteins expected in small populations (due to genetic drift) is offset by longer generation times (and vice versa), but in large populations with short generation times, noncoding DNA evolves faster while protein evolution is retarded by selection (which is more significant than drift for large populations).
In 1973, Ohta published a short letter in Nature
suggesting that a wide variety of molecular evidence supported the theory that most mutation events at the molecular level are slightly deleterious rather than strictly neutral. Between then and the early 1990s, many studies of molecular evolution used a "shift model" in which the negative effect on the fitness of a population due to deleterious mutations shifts back to an original value when a mutation reaches fixation. In the early 1990s, Ohta developed a "fixed model" that included both beneficial and deleterious mutations, so that no artificial "shift" of overall population fitness was necessary.
Neutral theory of molecular evolution
The neutral theory of molecular evolution states that the vast majority of evolutionary changes at the molecular level are caused by random drift of selectively neutral mutants . The theory was introduced by Motoo Kimura in the late 1960s and early 1970s...
that accounts for slightly advantageous or deleterious mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s at the molecular level. The nearly neutral theory was proposed by Tomoko Ohta
Tomoko Ohta
is a Japanese scientist working on molecular evolution. In 1956, she graduated from the University of Tokyo. After working on the neutral theory of evolution with her mentor, Motoo Kimura, she became convinced of the importance of the mutations that were nearly neutral. She developed the slightly...
in 1973 (including only deleterious mutations) and expanded in the early 1990s to include both advantageous and deleterious nearly neutral mutations. Unlike in Motoo Kimura
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...
's original neutral theory—which dealt only with mutations unaffected by natural selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
—the nearly neutral theory predicts a relationship between population size
Population size
In population genetics and population ecology, population size is the number of individual organisms in a population.The effective population size is defined as "the number of breeding individuals in an idealized population that would show the same amount of dispersion of allele frequencies under...
and the rate of molecular evolution
Molecular evolution
Molecular evolution is in part a process of evolution at the scale of DNA, RNA, and proteins. Molecular evolution emerged as a scientific field in the 1960s as researchers from molecular biology, evolutionary biology and population genetics sought to understand recent discoveries on the structure...
: in larger populations, genetic drift
Genetic drift
Genetic drift or allelic drift is the change in the frequency of a gene variant in a population due to random sampling.The alleles in the offspring are a sample of those in the parents, and chance has a role in determining whether a given individual survives and reproduces...
, which can bring even slightly deleterious mutations to fixation
Fixation (population genetics)
In population genetics, fixation is the change in a gene pool from a situation where there exist at least two variants of a particular gene to a situation where only one of the alleles remains...
, is a weaker force, so evolution happens more slowly than in smaller populations .
Origins of the nearly neutral theory
In the early 1970s, evolutionary biologists found that rates of proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
evolution (the "molecular clock
Molecular clock
The molecular clock is a technique in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation...
") are fairly independent of generation time, while rates of noncoding DNA
Noncoding DNA
In genetics, noncoding DNA describes components of an organism's DNA sequences that do not encode for protein sequences. In many eukaryotes, a large percentage of an organism's total genome size is noncoding DNA, although the amount of noncoding DNA, and the proportion of coding versus noncoding...
divergence are inversely proportional to generation time. Noting that population size is generally inversely proportional to generation time, Tomoko Ohta proposed that most amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
substitutions are slightly deleterious while noncoding DNA substitutions are more neutral. In this case, the faster rate of neutral evolution in proteins expected in small populations (due to genetic drift) is offset by longer generation times (and vice versa), but in large populations with short generation times, noncoding DNA evolves faster while protein evolution is retarded by selection (which is more significant than drift for large populations).
In 1973, Ohta published a short letter in Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
suggesting that a wide variety of molecular evidence supported the theory that most mutation events at the molecular level are slightly deleterious rather than strictly neutral. Between then and the early 1990s, many studies of molecular evolution used a "shift model" in which the negative effect on the fitness of a population due to deleterious mutations shifts back to an original value when a mutation reaches fixation. In the early 1990s, Ohta developed a "fixed model" that included both beneficial and deleterious mutations, so that no artificial "shift" of overall population fitness was necessary.