Nearly neutral theory of molecular evolution

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The nearly neutral theory of molecular evolution is a modification of the neutral theory of molecular evolution that accounts for slightly advantageous or deleterious mutations at the molecular level. The nearly neutral theory was proposed by Tomoko Ohta in 1973[1] (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 .

Origins of the nearly neutral theory

In the early 1970s, evolutionary biologists found that rates of protein 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).[2]

In 1973, Ohta published a short letter in Nature[3] 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.[4]


  1. Ohta, Tomoko (1973-11-09). "Slightly Deleterious Mutant Substitutions in Evolution". Nature. 246 (5428): 96–98. doi:10.1038/246096a0.
  2. Ohta, Tomoko (1996-04). "Development of Neutral and Nearly Neutral Theories". Theoretical Population Biology. 49 (2): 128–42. ISSN 0040-5809. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help), pp 130-131
  3. Ohta, Tomoko (1973-11-09). "Slightly Deleterious Mutant Substitutions in Evolution". Nature. 246 (5428): 96–98. doi:10.1038/246096a0.
  4. Ohta and Gillispie, "Development of Neutral and Nearly Neutral Theories", pp. 135-136

External links

The Nearly Neutral Theory of Molecular Evolution - Perspectives on Molecular Evolution