Home > Positioning > Persons > Ohta

Tomoko Ohta (1933–)

Ohta extended and refined Kimura’s neutral theory of molecular evolution by showing that the boundary between neutral and selected mutations is not sharp. Her nearly neutral theory (1973) argues that a large class of mutations are not strictly neutral but have selection coefficients so small that their fate is determined by the interaction of drift and weak selection — and that the relative importance of the two depends on effective population size. In large populations, slightly deleterious mutations are efficiently purged by selection; in small populations, they behave as if neutral and can drift to fixation. The nearly neutral theory resolved several empirical anomalies that the strict neutral theory could not explain and has become part of the standard framework of molecular evolution.

Life

Born 7 September 1933 in Miyoshi, Aichi Prefecture, Japan. Educated at the University of Tokyo (BS in agriculture, 1956). After graduating, she worked at the Kihara Institute for Biological Research, focusing on the cytogenetics of wheat and sugar beets. PhD at North Carolina State University (1966), under Ken-Ichi Kojima — where she shifted from plant cytogenetics to population genetics.

Joined Kimura’s Department of Population Genetics at the National Institute of Genetics in Mishima (1967) as a postdoctoral researcher. The collaboration with Kimura continued until his death in 1994; many of their key papers were co-authored. Ohta was the junior partner in the early years, but the nearly neutral theory was her independent contribution — building on Kimura’s framework while departing from his strict-neutrality assumption. Full professor at NIG (1984). Vice President of the National Institute of Genetics (1996–97).

Elected to the Japan Academy (2002). Foreign Associate of the National Academy of Sciences (USA, 2002). Crafoord Prize (2015, shared with Richard Lewontin) — the prize came late. Through the 1970s and 1980s, Kimura received the bulk of the attention for the neutral theory, while Ohta’s nearly neutral extension — which resolved the empirical anomalies the strict theory could not handle — was comparatively underrecognised. The pattern of credit distribution between Kimura and Ohta has been noted explicitly in the field: Kimura’s programme carried the name and the debate, while Ohta’s refinement quietly became the version that worked. The Crafoord Prize was the major institutional acknowledgment that the nearly neutral theory, not the strict neutral theory, was the lasting framework.

The nearly neutral theory

Kimura’s neutral theory (1968) proposed that the majority of molecular evolutionary change is selectively neutral — governed by random genetic drift rather than natural selection. The theory was powerful and parsimonious, but it faced empirical difficulties. Two in particular:

The generation-time effect. If molecular evolution is strictly neutral, the substitution rate should equal the neutral mutation rate per generation and be independent of generation time. But protein evolution appeared to proceed more slowly per year in organisms with long generation times (mammals) than in those with short generation times (rodents, Drosophila). The strict neutral theory could not explain this without invoking ad hoc differences in mutation rate.

Population-size effects on polymorphism. The neutral theory predicts that genetic diversity (heterozygosity) should be proportional to effective population size — large populations should be far more polymorphic than small ones. Observed differences in protein heterozygosity between species with very different population sizes were much smaller than the neutral prediction.

Ohta’s resolution: many mutations are not strictly neutral but nearly neutral — they have small deleterious effects (selection coefficients on the order of 1/2N_e, where N_e is the effective population size). In large populations, these mutations are efficiently removed by purifying selection and do not contribute to substitution. In small populations, the selection coefficient is too weak relative to drift, and the mutations behave as if neutral — drifting to fixation or loss. The rate of nearly neutral substitution therefore depends on population size: smaller populations accumulate more slightly deleterious substitutions. This explains the generation-time effect (organisms with small effective population sizes, often those with long generation times, have higher rates of nearly neutral substitution) and narrows the predicted difference in heterozygosity between large and small populations.

The framework was developed across a series of papers: “Slightly deleterious mutant substitutions in evolution” (Nature, 1973) was the foundational statement. Subsequent papers extended the theory to include slightly advantageous mutations, developed the mathematical treatment, and applied it to protein and DNA sequence data.

Where Ohta stops

The nearly neutral theory extended the neutral framework but retained its fundamental orientation: molecular evolution is primarily a stochastic process, with the great majority of substitutions being neutral or nearly neutral. The theory does not address adaptive molecular evolution — the fraction of substitutions driven by positive selection. Genomic studies since the 2000s have revealed that positive selection at the molecular level is more common than either the strict neutral theory or the nearly neutral theory predicted, particularly in species with large effective population sizes and in regulatory regions of the genome. The nearly neutral theory provides the null model against which adaptive evolution is measured, but the fraction of the genome subject to adaptive evolution — and the relative contributions of drift and positive selection to molecular divergence — is an empirical question the theory frames rather than answers.

The interaction between effective population size and the efficacy of selection that Ohta identified has been confirmed across many taxa, but the relationship is not always clean. Effective population size is difficult to estimate, varies across the genome (due to linked selection — hitchhiking and background selection), and may not be stable over evolutionary time. The nearly neutral theory’s quantitative predictions depend on N_e being known and roughly constant; in practice, both conditions are approximate.

Key works

See also: Kimura · Wright · Fisher · Darwinism