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Genes Born of ‘Junk DNA’ are Both Common and Beneficial

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2/17/2020

DUBLIN – Scientists from Trinity College Dublin and the University of Pittsburgh found that de novo gene birth — when new genes evolve from scratch — is a more common and plausible process than previously thought. 

 

Their findings appear in two studies — one publishing in eLIFE on February 18 at 8 a.m. GMT, and another published earlier this month in Nature Communications.

 

“It seems like a very large fraction of the genes that make species unique go through a de novo gene birth process” said Nature Communications study senior author Anne-Ruxandra Carvunis, Ph.D., assistant professor of computational systems biology at Pitt. 

 

In the eLIFE study, the researchers looked at “orphan genes,” so-called because they don’t appear to have evolved from parent genes. Often, orphan genes are the source of evolutionary innovations that allow organisms to adapt to unique challenges. For instance, an orphan gene unique to cod fish living in the arctic allows them to survive in sub-zero temperatures.

 

A lingering question surrounding orphan genes is where they came from. One idea is that they can originate de novo out of a region in the genome that is made up of non-coding “junk DNA.” Alternatively, with enough time, related genes can diverge so much that they no longer resemble one anther — a case of missing relatives.

 

“To our surprise, at most, around one third of orphan genes result from divergence,” said eLife study senior author Aoife McLysaght, Ph.D., professor of genetics at Trinity. “So, in turn, this suggests that most unique genes in the species we looked at are the result of other processes, including de novo emergence, which is therefore much more frequent than scientists initially thought.”

 

In the Nature Communications study, the researchers genetically engineered yeast to overexpress “proto-genes” that are in the process of emerging from non-coding DNA. 

 

The cells and colonies with extra proto-gene products often grew bigger, demonstrating that new genes, fashioned from scratch, could be beneficial to the yeast — a necessary aspect of natural selection.

 

When Carvunis and colleagues looked closer at proto-genes that proved beneficial, they frequently found codes for stable proteins that like to embed themselves in cell membranes, where they can perform essential functions like transport and communication.

 

“Order seems like something that’s hard to achieve, but our results go completely opposite to that,” Carvunis said. “We found that simple order is rampant everywhere in the genome. The propensity to make simple shapes that are stable is already there, waiting to be exposed.” De novo gene birth is becoming less and less mysterious as we better understand molecular innovation.”

 

Additional authors include Nikolaos Vakirlis, Ph.D., of Trinity College Dublin; Omer Acar, Nelson Castilho Coelho, M.S., Branden Van Oss, Ph.D., Aaron Wacholder, Ph.D., Ray Bowman, John Iannotta, Saurin Bipin Parikh, Carlos Camacho, Ph.D., Allyson O’Donnell, Ph.D., all of Pitt; Brian Hsu, Kate Medetgul-Ernar, Cameron Hines, Trey Ideker, Ph.D., of the University of California San Diego

 

These studies were funded by the European Research Council (309834 and 771419), National Institute of General Medical Sciences (R00GM108865, DP2GM137422, P41GM103504, 5R01GM097084 and F32GM129929), National Institute of Environmental Health Sciences (R01ES014811), National Science Foundation (1902859), and the Kinship Foundation Searle Scholars Program.