"Hundreds of natural selection studies could be wrong"

2 minute read

Happily, though, the study isn’t about our method for finding recent selection!

Instead, Masatoshi Nei and colleagues at Penn State have the long knives out for tests of selection based on excess amino acid substitutions:

Nei said that for many years he has suspected that the statistical methods were faulty. "The methods assume that when natural selection occurs the number of nucleotide substitutions that lead to changes in amino acids is significantly higher than the number of nucleotide substitutions that do not result in amino acid changes," he said. "But this assumption may be wrong. Actually, the majority of amino acid substitutions do not lead to functional changes, and the adaptive change of a protein often occurs by a rare amino acid substitution. For this reason, statistical methods may give erroneous conclusions." Nei also believes that the methods are inaccurate when the number of nucleotide substitutions observed is small.

Well, that’s not us – we’re studying much more recent events, based on linkage disequilibrium. Hey, the observation that selection was rare through most of human evolution actually strongly supports our observation that the recent rate of selection represents a massive acceleration over the long-term rate.

Still, I’m skeptical about Nei’s conclusions. According to the press release, they identify a number of cases in which sites inferred to be under selection are actually not the functional change, because other functional changes have been identified by experiment. That’s hardly a general argument that selection has been overcounted in these analyses.

I find that in most counts of selection based on amino acid substitutions, the criteria for counting selection are ridiculously conservative. Often, you see the inference of selection only for cases where the number of amino acid changes actually exceed the number of silent changes. That’s silly – there’s a strong bias against amino acid substitutions because of purifying selection. Only in repeated instances of positive selection are you ever going to see more amino acid substitutions than silent ones.

Meanwhile, the press release mis-states some research into human-chimpanzee genetic differences:

"These statistical methods have led many scientists to believe that natural selection acted on many more genes in humans than it did in chimpanzees, and they conclude that this is the reason why humans have developed large brains and other morphological differences," said Nei. "But I believe that these scientists are wrong. The number of genes that have undergone selection should be nearly the same in humans and chimps. The differences that make us human are more likely due to mutations that were favorable to us in the particular environment into which we moved, and these mutations then accumulated through time."

In fact, Margaret Bakewell and colleagues (2007) in the same journal showed that chimpanzees have more selected amino acid substitutions than humans. Nei’s got it completely backward.

Now, I think Bakewell and colleagues might be wrong. The chimpanzee genome draft had many more sequencing artifacts at that time than the human genome, and these might account for the apparent excess in chimpanzees. But it’s simply not true that researchers have shown “many more genes” under selection in humans than chimpanzees.

Well, except for us, referring to very recent human evolution. But in that case, as Nei notes, we’re talking about “mutations that were favorable to us in the particular environment into which we moved.” It’s the massive environmental and demographic changes of the last 50,000 years that have made the difference. For most of the six million years before that, human genetic evolution seems to have gone at almost the same rate as in chimpanzees.

(via Gene Expression)