Nearly Neutral Theory

The nearly neutral theory of molecular evolution is an extension of Kimura's neutral theory, proposed principally by Tomoko Ohta. It argues that a large fraction of mutations are not strictly neutral but nearly neutral — their selective coefficients are so small that whether they are fixed by selection or eliminated by drift depends on population size. In large populations, even weak selection is effective; in small populations, even moderately deleterious mutations can fix by drift.

The nearly neutral theory dissolves the sharp dichotomy between 'adaptive evolution' and 'neutral evolution' into a continuous spectrum mediated by effective population size. It predicts that mutation accumulation — including slightly deleterious mutations — should be faster in lineages with small effective population sizes, a prediction supported by comparative genomics across organisms ranging from bacteria to vertebrates.

The theory has uncomfortable implications for conservation biology and evolutionary medicine: human effective population sizes are small enough that slightly deleterious mutations accumulate in our genomes at rates that selection cannot prevent. Whether this constitutes mutational meltdown in the long term is contested. That it is happening is not.