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Study sheds light on evolution of human complexity
Date:11/3/2009

tner proteins to form complexes.

"These poorly packed proteins are potential troublemakers when gene duplication occurs," Fernandez said. "The paralog encodes more copies of the protein than the body needs. This is called a 'dosage imbalance,' and it can make us sick. For instance, dosage imbalance has been implicated in Alzheimer's and other diseases."

Given selection inefficiency, Fernandez knew that paralogs encoding poorly packed proteins could remain in the human genome for quite a while. So he and graduate student Jianpeng Chen decided to examine whether gene duplicates had remained in the genome long enough for random genetic mutations to affect the paralogs dissimilarly. Fernandez and Chen, now a senior researcher in Beijing, China, cross-analyzed databases on genomics, protein structure, microRNA regulation and protein expression in such troublesome paralogs.

"The longer these duplicate genes stick around due to inefficient selection, the more likely they are to suffer a random mutation," Fernandez said. "Portions of every gene act to regulate protein expression -- by binding with microRNA, for example. We found numerous instances where random mutations had caused paralogs to be expressed dissimilarly, in ways that removed detrimental dosage imbalances."

Lynch said one aspect of Fernandez's research that is potentially groundbreaking is the observed tendency of proteins to evolve a more open structure in complex organisms.

"This observation fits with the general theory that large organisms with relatively small population sizes -- compared to microbes -- are subject to the vagaries of random genetic drift and hence the accumulation of very mildly deleterious mutations," Lynch said.

In principle, he said, the accumulation of such mutations may encourage a slight breakdown in protein stability. This, in turn, opens the door to interactions with other proteins that can return a measure of that lost stabilit
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Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert

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