Study sheds light on evolution of human complexity

Scientists find new evolutionary mechanism that takes advantage of inefficient selection

HOUSTON -- (Nov. 3, 2009) -- A painstaking analysis of thousands of genes and the proteins they encode shows that human beings are biologically complex, at least in part, because of the way humans evolved to cope with redundancies arising from duplicate genes.

"We have found a specific evolutionary mechanism to account for a portion of the intricate biological complexity of our species," said Ariel Fernandez, professor of bioengineering at Rice University. "It is a coping mechanism, a process that enables us to deal with the fitness consequences of inefficient selection. It enables some of our proteins to become more specialized over time, and in turn makes us more complex."

Fernandez is the lead author of a paper slated to appear in the December issue of the journal Genome Research. The research is available online now.

Fernandez said the study drew from previous findings by his own research group and from seminal work of Michael Lynch, Distinguished Professor of Biology at Indiana University and a recently elected a fellow of the National Academy of Science. Lynch's work has shown that natural selection is less efficient in humans as compared with simpler creatures like bacteria. This "selection inefficiency" arises from the smaller population size of humans as compared with unicellular organisms.

"In all organisms, genes get duplicated every so often, for reasons we don't fully understand," Fernandez said. "When working efficiently, natural selection eliminates many of these duplicates, which are called 'paralogs.' In our earlier work, we saw that an unusual number of gene duplicates had survived in the human genome, which makes sense given selection inefficiency in humans."

In prior research on protein structure, Fernandez's team found that some proteins are packaged more poorly than others. Moreover, they found that the least-efficiently packed proteins are structurally stable only when they bind with partner 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.