Professors study evolutionary novelty

Harvard professor Andrew W. Murray’s recent article in Current Biology explains how loss-of-function mutations might lead to evolutionary novelty. 

Andrew Murray is the Herchel Smith Professor of Molecular Genetics, and director of the John Harvard Distinguished Science Fellows Program. In the Current Biology piece, he examines the question if easier to access loss-of-function mutations could cause speciation into specific ecological niches. He presents the one-by-one and piggyback models to examine small and large populations, respectively.

“Evolutionary novelty is difficult to define. It typically involves shifts in organismal or biochemical phenotypes that can be seen as qualitative as well as quantitative changes,” Murray wrote in the article introduction. “In laboratory-based experimental evolution of novel phenotypes and the human domestication of crops, the majority of the mutations that lead to adaptation are loss-of-function mutations that impair or eliminate the function of genes rather than gain-of-function mutations that increase or qualitatively alter the function of proteins.

“Here, I speculate that easier access to loss-of-function mutations has led them to play a major role in the adaptive radiations that occur when populations have access to many unoccupied ecological niches,” he wrote. “I discuss five possible objections to this claim: that genes can only survive if they confer benefits to the organisms that bear them, antagonistic pleiotropy, the importance of pre-existing genetic variation in populations, the danger that adaptation by breaking genes will, over long times, cause organisms to run out of genes, and the recessive nature of most loss-of-function mutations.”

In a 2016 profile published by the National Center for Biotechnology Information, Murray said he studies evolution in the laboratory to master the process of natural selection and learn if mutations that disrupt genes cause greater change than incremental gain-of-function evolutionary processes.

“We’re really interested in looking at evolution in the natural world to try to find examples where traits evolved recently enough to ask whether it was by mutations that destroyed the function of genes or improved the genes,” he said.

Michael Behe, a Lehigh University biochemistry professor, has also written on this topic and provided his thoughts on Murray’s article.

Behe, the author of “Darwin Devolves,” offered a brief explanation of his 2019 book.

“In a nutshell, Darwin’s mechanism of random mutation and natural selection does work as described,” he told Current Science Daily. “The surprising discovery that has been made possible by advances in DNA sequencing techniques, however, is that the large majority of adaptive mutations are ones that break or degrade genes. That means Darwin’s mechanism is, ironically, powerfully devolutionary. It works chiefly by squandering genetic information for short-term gain.”

Behe uses the phrase “first rule of adaptive evolution,” and explained how that can be linked to Murray’s views on loss-of-function mutations.

“In everyday language, the ‘First Rule of Evolution’ says that, if reducing the activity of a pre-existing gene can help a species survive, then mutations which break or degrade that gene will quickly spread in the population through natural selection until the entire species has lost that gene,” he said. “Yes, the ‘first rule’ fits well with Professor Murray’s essay. He writes that evolution has ‘easier access to loss-of-function mutations’ — that is exactly what the first rule is about.”

Behe said degradative mutations are easy to produce and therefore dominate evolution — in fact, sometimes losing a gene can help survival.

“It is statistically very likely that a change to a pre-existing gene will degrade or destroy its activity, just as it is very likely that a random change to, say, a computer will damage it,” he said. “It is statistically quite unlikely that a random change will improve the workings of either a computer or a gene. “

Behe in a June 18, 2014 New York Times story provided an example of a degradative mutation that helps humans:

“One gene, APOC3, stood out. The scientists found four mutations that destroyed the function of this gene. The Amish study had discovered that people with such a mutation could drink a big, rich milkshake, loaded with fat, and their triglyceride levels did not budge. For everyone else, they spiked. The new studies show what that means for people's health.” 

People who inherited the destroyed gene had much less chance of having heart disease, Behe said.

“With our modern diet, it becomes beneficial to lose that gene,” he said.

Behe said he and Murray have differing conclusions on some points.

“I do agree with him insofar as he argues that adaptive loss-of-function mutations are a lot easier to produce than constructive mutations,” he said. “I doubt, however, that such LOF mutations would add up to ‘evolutionary novelty’ — which I would define as a new biological classification of family or higher. Unfortunately, he does not point to any examples where such a process seems to have occurred.”

When “Darwin Devolves” was published, the response was swift and highly critical. 

He has posted links to their reviews, along with his rebuttals on the book website, darwindevolves.com.

Behe also disagrees that constructive mutations will have a role in adaptive evolution.

“If by ‘constructive mutation’ is meant a mutation that arises randomly and can lead to substantially new biochemical machinery in the cell then, no, I don’t think so,” Behe said. “For the reasons I discuss in my books, I think construction of substantial new biochemical machinery requires intelligent design.”