The neutral theory of molecular evolution
holds that at the molecular level most evolutionary
changes and most of the variation within and
between species is not caused by natural selection
but by genetic drift of mutant alleles that
are neutral.
A neutral mutation is one that does not affect
an organism's ability to survive and reproduce.
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.
Mutations that are not deleterious are assumed
to be mostly neutral rather than beneficial.
In addition to assuming the primacy of neutral
mutations, the theory also assumes that the
fate of neutral mutations is determined by
the sampling processes described by specific
models of random genetic drift.The theory
was introduced by the Japanese biologist Motoo
Kimura in 1968, and independently by two American
biologists Jack Lester King and Thomas Hughes
Jukes in 1969, and described in detail by
Kimura in his 1983 monograph The Neutral Theory
of Molecular Evolution.
According to Kimura, the theory applies only
for evolution at the molecular level, and
phenotypic evolution is controlled by natural
selection, as postulated by Charles Darwin.
The proposal of the neutral theory was followed
by an extensive "neutralist-selectionist"
controversy over the interpretation of patterns
of molecular divergence and polymorphism,
peaking in the 1970s and 1980s.
Since then, much evidence has been found for
selection at molecular level.
== Overview ==
While some scientists, such as Freese (1962)
and Freese and Yoshida (1965), had suggested
that neutral mutations were probably widespread,
a coherent theory of neutral evolution was
proposed by Motoo Kimura in 1968, and by King
and Jukes independently in 1969.Kimura, King,
and Jukes suggested that when one compares
the genomes of existing species, the vast
majority of molecular differences are selectively
"neutral", i.e. the molecular changes represented
by these differences do not influence the
fitness of organisms.
As a result, the theory regards these genomic
features as neither subject to, nor explicable
by, natural selection.
This view is based in part on the degenerate
genetic code, in which sequences of three
nucleotides (codons) may differ and yet encode
the same amino acid (GCC and GCA both encode
alanine, for example).
Consequently, many potential single-nucleotide
changes are in effect "silent" or "unexpressed"
(see synonymous or silent substitution).
Such changes are presumed to have little or
no biological effect.
A second hypothesis of the neutral theory
is that most evolutionary change is the result
of genetic drift acting on neutral alleles,
rather than for example genetic hitchhiking
of a neutral allele due to genetic linkage
with non-neutral alleles.
After appearing by mutation, a neutral allele
may become more common within the population
via genetic drift.
Usually, it will be lost, or in rare cases
it may become fixed, meaning that the new
allele becomes standard in the population.
This stochastic process is assumed to obey
equations describing random genetic drift
by means of accidents of sampling.
According to the neutral theory, mutations
appear at rate μ in each of the 2N copies
of a gene, and fix with probability 1/(2N).
This means that if all mutations were neutral,
the rate at which fixed differences accumulate
between divergent populations is predicted
to be equal to the per-individual mutation
rate, e.g. during errors in DNA replication;
both are equal to μ.
When the proportion of mutations that are
neutral is constant, so is the divergence
rate between populations.
This provides a rationale for the molecular
clock, although the discovery of a molecular
clock predated neutral theory.Many molecular
biologists and population geneticists also
contributed to the development of the neutral
theory, which is different from the neo-Darwinian
theory.Neutral theory does not deny the occurrence
of natural selection.
Hughes writes: "Evolutionary biologists typically
distinguish two main types of natural selection:
purifying selection, which acts to eliminate
deleterious mutations; and positive (Darwinian)
selection, which favors advantageous mutations.
Positive selection can, in turn, be further
subdivided into directional selection, which
tends toward fixation of an advantageous allele,
and balancing selection, which maintains a
polymorphism.
The neutral theory of molecular evolution
predicts that purifying selection is ubiquitous,
but that both forms of positive selection
are rare, whereas not denying the importance
of positive selection in the origin of adaptations."
In another essay, Hughes writes: "Purifying
selection is the norm in the evolution of
protein coding genes.
Positive selection is a relative rarity—but
of great interest, precisely because it represents
a departure from the norm."
A more general and more recent view of molecular
evolution is presented by Nei.
== The "neutralist–selectionist" debate
==
A heated debate arose when Kimura's theory
was published, largely revolving around the
relative percentages of alleles that are "neutral"
versus "non-neutral" in any given genome.
Contrary to the perception of many onlookers,
the debate was not about whether natural selection
does occur.
Kimura argued that molecular evolution is
dominated by selectively neutral evolution
but at the phenotypic level, changes in characters
were probably dominated by natural selection
rather than genetic drift.According to the
neutral theory of molecular evolution, the
amount of genetic variation within a species
should be proportional to the effective population
size.
Levels of genetic diversity vary much less
than census population sizes, giving rise
to the "paradox of variation" . 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.
Tomoko Ohta emphasized the importance of nearly
neutral mutations, in particularly slightly
deleterious mutations.
The population dynamics of nearly neutral
mutations is essentially the same as that
of neutral mutations unless the absolute magnitude
of the selection coefficient is greater than
1/N, where N is the effective population size
with respect to selection.
The value of N may therefore affect how many
mutations can be treated as neutral and how
many as deleterious.
There are a large number of statistical methods
for testing whether neutral theory is a good
description of evolution (e.g., McDonald-Kreitman
test), and many authors claimed detection
of selection (Fay et al. 2002, Begun et al.
2007, Shapiro et al. 2007, Hahn 2008, Akey
2009.).
However, Nei et al. (2010). have argued that
their methods for claiming so depend on many
assumptions which are not biologically justified.
== See also ==
Adaptive evolution in the human genome
Coalescent theory
Masatoshi Nei
Motoo Kimura
Molecular evolution
Nearly neutral theory of molecular evolution
Tomoko Ohta
Unified neutral theory of biodiversity
