The theory of evolution by natural selection, first formulated in Darwin’s book “On the Origin of Species” in 1859, is the process by which organisms change over time as a result of changes in heritable physical or behavioural traits (Darwin 1859 reviewed by Than 2018). Changes that allow an organism to better adapt to its environment will help it survive and have more offspring.

The theory has two main points, said Brian Richmond, Curator of Human Origins at the American Museum of Natural History in New York City. “All life on Earth is connected and related to each other,” and this diversity of life is a product of “modifications of populations by natural selection, where some traits were favoured in an environment over others,” he said. More simply put, the theory can be described as “descent with modification,” said Briana Pobiner, an anthropologist and educator at the Smithsonian Institution, National Museum of Natural History in Washington, DC.

Darwin accepts the limitation of his theory as follows under Chapter VI, Organs of extreme perfection: It is scarcely possible to avoid comparing the eye to a telescope. We know that this instrument has been perfected by the long-continued efforts of the highest human intellects; and we naturally infer that the eye has been formed by a somewhat analogous process.

We must suppose that there is a power always intently watching each slight accidental alteration in the transparent layers; and carefully selecting each alteration which, under varied circumstances, may, in any way, or in any degree, tend to produce a distinctive image.

May we not believe that a living optical instrument might thus be formed as superior to one of glass, as the works of the Creator are to those of man? If it could be demonstrated that any complex organ existed, which could not possibly have been formed by numerous, successive, slight modifications, my theory would absolutely break down.

Challenged by geneticists

The Theory of Evolution presented by Charles Darwin was critically reviewed (Callier 2018). 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 favourable adaptations, he suggested, allowed ancient ancestral forms to gradually diversify into countless species.

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).

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 emphasised the importance of random genetic changes in the course of evolution. Nevertheless, neutral theory was rapidly adopted by many biologists. This was partly the 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.

Today, half a century after Kimura’s article, more affordable genomic sequencing and sophisticated statistical methods are allowing evolutionary theorists to make headway on quantifying the contribution of adaptive variation and neutral evolution to species differences. In species like humans and fruit flies, the data have revealed extensive selection and adaptation, which has led to strong pushback against Kimura’s original idea, at least by some researchers.

In a paper published in late October 2018 in the Journal of the National Cancer Institute, Townsend and his Yale colleagues presented the results of their evolutionary analysis of mutations in cancers. Although identifying the mutations undergoing the strongest selection is clearly useful and important, selection can also have subtle but important indirect effects on regions of the genome neighbouring the target of selection.

The first hint of these indirect effects came in the 1980s and ’90s with the advent of the polymerase chain reaction, a technique that enabled researchers to look at nucleotide-level variation in gene sequences for the first time. One thing they discovered was an apparent correlation between the level of genetic variation and the rate of recombination at any specified region of the genome.

Andrew Kern is 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.

By 2005, researchers could get whole-genome data from a variety of organisms, and they started to find this apparent correlation between levels of genetic variation and the rates of recombination everywhere, Kern said. That correlation meant that forces beyond direct purifying selection and neutral drift were creating differences in levels of variation across the genomic landscape.

Kern argues that the differences in the rates of recombination across the genome reveal a phenomenon called genetic hitchhiking. When beneficial alleles are closely linked to neighbouring neutral mutations, natural selection tends to act on all of them as a unit.

In humans, recent evidence suggests “there’s a lot more adaptation than we ever thought was present,” Kern said. Recent human evolution is largely a history of migrations to new geographical locations where humans encountered new climates and pathogens to which they had to adapt.

In 2017, Kern published a paper showing that most human adaptations arose from existing genetic variation within the genome, not novel mutations that spread rapidly through the population.

In other words, it’s yet another non-neutral mechanism affecting genome evolution. As useful as the neutral theory has been in its various forms over the past half-century, the future of evolutionary theory may inevitably depend on finding ever-better ways to do the hard work of figuring out exactly how — and how much — selection is inexorably shaping our genomes after all.


  1. Callier V, 2018. Theorists Debate How ‘Neutral’ Evolution Really Is? Quanta Magazine, November 8.
  2. Than Key 2018. What is Darwin’s Theory of Evolution? Live Science.