MN: Every part of our body is controlled by molecules, so you have to explain on a molecular level. That is the real mechanism of evolution, how molecules change. They change through mutation. Mutation means a change in DNA through, for example, substitution or insertion [of nucleotides]. First you have to have change, and then natural selection may operate or may not operate. I say mutation is the most important, driving force of evolution. Natural selection occurs sometimes, of course, because some types of variations are better than others, but mutation created the different types. Natural selection is secondary.
Someone on the outside looking in at the debate might say you and other researchers are splitting hairs, that both mutation and natural selection drive evolution. How do you respond?
MN: I don’t study the character or the function; I study the gene that controls it. My position is mutation creates variation, then natural selection may or may not operate, it may or may not choose the good variation and eliminate the bad one, but natural selection is not the driving force.
In neo-Darwinism, evolution is a process of increasing fitness [in the sense of an organism’s ability both to survive and to reproduce]. In mutation-driven evolutionary theory, evolution is a process of increasing or decreasing an organism’s complexity. We tend to believe natural selection selects one type. But there are many types, and still they’re OK. They can survive, no problem.
For example, if blue eyes are better for some reason in Scandinavia, that mutation has a selected advantage, and then of course that advantage will occur more in that population. But first you have to have the mutation. And natural selection itself is not so clear. In certain cases it is, but not always. The gene frequency of blue eyes may have increased by chance, too, rather than natural selection. The blue eye color may be just as good as green. Both can see.
In 1968, your friend and mentor Motoo Kimura proposed the neutral theory of molecular evolution, arguing that most mutations that occur have neither advantageous nor deleterious consequences for an organism. How did you take neutral theory a step further with mutation-driven evolutionary theory?
MN: Kimura believed morphology [appearance] evolves through natural selection. He applied neutral theory only on a molecular level. I say it can determine morphological characteristics as well because DNA determines everything, but to prove this has not been so easy. [Laughs.] Forty or 50 years later, I am still trying to prove it.
One of your most significant contributions to the field is Nei’s standard genetic distance, a formula that determines when different populations diverged based on mathematical analysis of their genomes. But this formula assumes the rate of genetic change is constant. Do you think human activity — from overfishing to burning fossil fuels to illuminating our cities and highways with artificial light — could be speeding up the rate of mutation?
MN: I think there is a mutagenic element to human activity, but it’s difficult to gather proof. It’s occurred only in, say, the past 10,000 years, and I don’t know if it’s changing the rate of mutation. You can identify how many different mutations occurred, but not always how.
You’ve been talking about mutation-driven evolution for more than three decades. Why do you think the majority of evolutionary biologists remain in the natural selection camp?
MN: I expressed this simple view first in 1975 in my book Molecular Population Genetics and Evolution, and in 1987 in a chapter in another book, but no one changed their views or the textbooks. Of course, at that time, molecular biology had not developed too far yet, and traditional evolutionary biology only considered morphology, not how the variation occurred.
Some birds, for example, have a variant of hemoglobin that allows them to fly over the Himalayas, at very high altitudes. Some alligators have a different variant of hemoglobin that allows them to stay submerged for a very long time. This has been known for a while and everyone felt, well, variation exists in the populations, but the condition necessary must be just natural selection.
In 1987, you co-authored a paper with Naruya Saitou describing the neighbor-joining method, a novel algorithm for creating evolutionary trees by working backward based on key genetic differences between related species, the idea being the more recently one species diverged from another, the more similar their DNA will be. It’s been cited more than 34,000 times over the years and has become a cornerstone of molecular evolutionary biology research. Why do you feel it was so influential?