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Sunday, September 26, 2021

Doubling down on genetic change

In many ways, biological evolution at the molecular scale is a series of small steps. But scientists have not agreed on exactly how those steps add up to create entirely new genes, the molecular sequences on DNA that code for an organism’s vital functions.

By conducting controlled evolution on a strain of Salmonella bacteria, a team of researchers from UC Davis and the University of Uppsala in Sweden have shown for the first time how this process can occur when existing genes are duplicated and subsequently diverge into two separate genes — the original and the new variant. The results were published in the Oct. 19 issue of Science.

“It seems pretty clear that genes duplicate, that new genes evolve, and that they evolve by duplication of old genes, and then divergence of the two copies,” said John Roth, a UC Davis microbiology professor and co-author of the study. “People have suggested that this problem of duplication and divergence is simple, but it actually raises serious problems.”

Unlike evolutionary events caused by the mutation of single genes, duplication can lead to the creation of an entirely new gene while leaving the original unaltered. Convention holds that the initial duplication is a chance event, leaving the new copy free to pick up potentially beneficial mutations that could eventually lead to a new function. The problem, says Roth, is that the rough and tumble of molecular interactions along the genome tends to eliminate duplicate genes before they can be enhanced through mutation.

“You need to hold that extra copy long enough for the slow process of giving that gene an extra function to occur,” Roth said.

To get around this dilemma, Roth and his colleagues proposed in 2007 a model of gene evolution they call Innovation, Amplification, and Divergence (IAD). The model was based on laboratory evidence that had established two key findings: that genes can acquire mutations for weak secondary “side activities” in addition to their main function, and that duplication is the most common way to increase gene expression when the new side activities are favored by natural selection.

Enter the IAD model, where an initial gene mutation prior to duplication adds a slight secondary function (the “innovation”). This marginal modification is then amplified through duplication when a change in environmental conditions makes it suddenly beneficial. This process continues until there is a gene copy that has been sufficiently improved — has “diverged” from the original — to perform the new function without needing further amplification.

“It’s a real maelstrom of interactions that lets the sequence improve,” Roth said. “But you get a bigger target for mutations when you get lots of copies, any one of which can pick up a beneficial mutation.”

Researchers in Dan Andersson’s laboratory in Sweden induced a strain of Salmonella bacteria to evolve a new gene for a specific enzyme involved in amino acid synthesis. The experiment allowed the researchers to observe gene evolution in real time.

“What’s nice about their paper is that it’s one of the first experimental approaches to the problem,” said Michael Lynch, a biology professor at Indiana University who researches gene evolution. “It’s premature to say that this is the only mechanism that leads to the expansion and preservation of duplicate genes, but they’ve made a pretty good case that this is one of the mechanisms.”

Andersson said they hope to try experiments with yeast next.

“The difficulty is finding suitable enzymes … that we can select for, but we think we might have solved that,” Andersson wrote in an email.

Ultimately, says Roth, this work may lead to practical uses in making enzymes with novel functions. But many questions remain concerning the basic biology behind gene evolution, including the extent of the similarities between bacteria and the rest of the living world.

OYANG TENG can be  reached at science@theaggie.org.

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