Young genes correlated with evolution of human brain

(Press-News.org) Young genes that appeared after the primate branch split off from other mammal species are more likely to be expressed in the developing human brain, a new analysis finds. The correlation suggests that evolutionarily recent genes, which have been largely ignored by scientists thus far, may be responsible for constructing the uniquely powerful human brain. The findings are published October 18 in the online, open access journal PLoS Biology.

"We found that there is a correlation between new gene origination and the evolution of the brain," said senior author Manyuan Long, PhD, Professor of Ecology & Evolution at the University of Chicago. "There are some 50 to 60 human-specific genes in the frontal cortex of the brain, the part that makes humans diverge with other non-human primates."

Scientists have long sought to solve the riddle of how the human brain evolved the unique anatomy and functional capacity that separate us from our primate ancestors. With the completion of the Human Genome Project and the growing availability of genome sequences for our primate relatives and other species, researchers have looked to genetics for answers. From these studies, many scientists have hypothesized that differential regulation of conserved genes shared across species, rather than the arrival of new, species-specific protein-encoding genes, was responsible for the dramatically different human brain.

However, in a 2010 study, Long's laboratory discovered that the younger, species-specific genes could be just as important to an organism's development as older, conserved genes. For the new paper in PLoS Biology, first author Yong Zhang, PhD, and colleagues merged a database of gene age with transcription data from humans and mice to look for when and where young genes, specific to each species, are expressed. The researchers found that a higher percentage of primate-specific young genes were expressed in brain than mouse-specific young genes. Human-specific young genes were also more likely to be seen in fetal brain, when the organ is developing, and in the brain structures uniquely elaborated in primates such as neocortex and prefrontal cortex.

The authors stress that their finding is only a correlation between the appearance of young, human-specific genes and the evolutionary appearance of advanced brain structures. Future research will look at the function of these genes and the role they may have played in building the unique human brain. One intriguing feature is that many of the new genes appear to code for novel proteins, rather than merely tweaking the regulation of older, conserved proteins.

"Traditionally, people don't believe that a new protein or new gene can play any role in an important process. Most people only pay attention to the regulation of genes," Long said. "But out of a total of about 1,300 new genes, only 13 percent were involved in new regulation. The rest, some 1,100 genes, are new genes that bring a whole new type of function."

### Funding: The authors were supported by a US National Institutes of Health grant (NIH R0IGM078070-01A1), the NIH ARRA supplement grant (R01 GM078070-03S1), the National Science Foundation grant (MCB-1051826), and Chicago Biomedical Consortium with support from The Searle Funds at The Chicago Community Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Citation: Zhang YE, Landback P, Vibranovski MD, Long M (2011) Accelerated Recruitment of New Brain Development Genes into the Human Genome. PLoS Biol 9(10): e1001179. doi:10.1371/journal.pbio.1001179