When Charles Darwin articulated his theory of evolution by natural selection in On the Origin of Species in 1859, he focused on adaptations—the changes that enable organisms to survive in new or changing environments. Selection for favorable adaptations, he suggested, allowed ancient ancestral forms to gradually diversify into countless species.

That concept was so powerful that we might assume evolution is all about adaptation. So it can be surprising to learn that for half a century, a prevailing view in scholarly circles has been that it’s not.

Selection isn’t in doubt, but many scientists have argued that most evolutionary changes appear at the level of the genome and are essentially random and neutral. Adaptive changes groomed by natural selection might indeed sculpt a fin into a primitive foot, they said, but those changes make only a small contribution to the evolutionary process, in which the composition of DNA varies most often without any real consequences.

But now some scientists are pushing back against this idea, known as neutral theory, saying that genomes show much more evidence of evolved adaptation than the theory would dictate. This debate is important because it affects our understanding of the mechanisms that generate biodiversity, our inferences about how the sizes of natural populations have changed over time and our ability to reconstruct the evolutionary history of species (including our own). What lies in the future might be a new era that draws from the best of neutral theory while also recognizing the real, empirically supported influence of selection.

An 'Appreciable Fraction' of Variation

Darwin’s core insight was that organisms with disadvantageous traits would slowly be weeded out through negative (or purifying) selection, while those with advantageous features would reproduce more often and pass those features on to the next generation (positive selection). Selection would help to spread and refine those valuable traits. For most of the first half of the 20th century, population geneticists largely attributed genetic differences between populations and species to adaptation through positive selection.

Motoo Kimura proposed in 1968 that most mutations might be neutral in effect rather than beneficial or harmful, and that shifts in the frequency of these neutral mutations dominated evolutionary change at the genomic level. Annual Reviews

But in 1968, the famed population geneticist Motoo Kimura resisted the adaptationist perspective with his neutral theory of molecular evolution. In a nutshell, he argued that an “appreciable fraction” of the genetic variation within and between species is the result of genetic drift — that is, the effects of randomness in a finite population — rather than natural selection, and that most of these differences have no functional consequences for survival and reproduction.

The following year, the biologists Jack Lester King and Thomas Jukes published “Non-Darwinian Evolution,” an article that likewise emphasized the importance of random genetic changes in the course of evolution. A polarized debate subsequently emerged between the new neutralists and the more traditional adaptationists. Although everyone agreed that purifying selection would weed out deleterious mutations, the neutralists were convinced that genetic drift accounts for most differences between populations or species, whereas the adaptationists credited them to positive selection for adaptive traits.

Much of the debate has hinged on exactly what Kimura meant by “appreciable fraction” of genetic variation, according to Jeffrey Townsend, a biostatistician and professor of evolutionary biology at the Yale School of Public Health. “Is that 50 percent? Is it 5 percent, 0.5 percent? I don’t know,” he said. Because Kimura’s original statement of the theory was qualitative rather than quantitative, “his theory could not be invalidated by later data.”

Nevertheless, neutral theory was rapidly adopted by many biologists. This was partly a result of Kimura’s reputation as one of the most prominent theoretical population geneticists of the time, but it also helped that the mathematics of the theory was relatively simple and intuitive. “One of the reasons for the popularity of the neutral theory was that it made things a lot easier,” said Andrew Kern, a population geneticist now at the University of Oregon, who contributed an article with Matthew Hahn, a population geneticist at Indiana University, to a special issue of Molecular Biology and Evolution celebrating the 50th anniversary of neutral theory.