What made the human brain? According to Stanley Kubrick and Arthur C. Clarke, it was a giant obsidian monolith inspiring primates to use tools and weapons. Scientists have taken a more nuanced approach, looking for the biology behind the complex structures and enhanced function of the human brain. But merely comparing the genes expressed in adult human brains to those of other animals yielded few promising differences, leading scientists to focus on changes in the regulation of old genes rather than the arrival of new genes. After all, the construction of a structure as important as the brain cannot rely on unpredictable, novel genes with new functions, right?
However, those young genes are recently taking on a higher profile. In a 2010 paper, the University of Chicago laboratory of Manyuan Long demonstrated that new genes exclusive to a given species can be just as critical to an organism’s survival as the old, conserved genes it shares with other species. The implication at the time was that what makes us uniquely human could lie in those “young” genes that only appeared in our genome relatively recently.
“Animal models have proven to be very useful and important for dissecting human disease,” said Sidi Chen in 2010 about that study. “But if our intuition is correct, some important health information for humans will reside in the unique parts of the human genome.”
A new study from Long’s lab appearing yesterday in PLoS Biology identifies one important place where those new genes may play role: the human brain. By merging a database of gene age with gene transcription data from humans and mice, researchers looked for where young genes specific to each species were expressed.They found that a higher percentage of primate-specific young genes were expressed in the brain compared to mouse-specific young genes. Human-specific young genes also were more likely to be expressed in uniquely human brain structures, such as the neocortex and prefrontal cortex.
“Newer genes are found in newer parts of the human brain,” said Yong Zhang, PhD, postdoctoral researcher and first author on the study. “We know the brain is the most remarkable difference between humans and other mammals and primates. These new genes are a candidate for future studies, as they are more likely to underlie this difference.”
Another intriguing finding in the gene age data was inspired by Zhang’s visit to the obstetrician with his pregnant wife. While viewing an ultrasound of his unborn child, Zhang said he realized that much of human development takes place during fetal stages – suggesting those early months should be a critical time for gene expression. As predicted, young human-specific genes in the brain were more likely to be turned on during fetal or infant development.The early activity of these genes suggests scientists should be looking at earlier developmental stages for genetic activity that ultimately shapes the complexity of the human brain.
“What’s really surprising is that the evolutionary newest genes on the block act early,” said co-author Patrick Landback, a graduate student in Long’s laboratory. “The primate-specific genes act before birth, even when a human embryo doesn’t look very different from a mouse embryo. But the actual differences are laid out early.”
Importantly, the analysis does not pinpoint exactly which genes explain the appearance of the human brain. For now, it is only a correlation between the appearance of young human-specific genes and the evolutionary appearance of advanced brain structures. But the data does suggest that scientists looking for the origin of the human brain should look at the laregely-neglected newer genes instead of those conserved across species.
“Traditionally, people don’t believe that a new protein or a new gene can play any role in an important process. Most people pay attention to only 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.”
(Image: Todd Preuss, Yerkes Primate Research Center, Molecular Insights into Human Brain Evolution. Bradbury J PLoS Biology 3/3/2005)
Zhang, Y., Landback, P., Vibranovski, M., & Long, M. (2011). Accelerated Recruitment of New Brain Development Genes into the Human Genome PLoS Biology, 9 (10) DOI: 10.1371/journal.pbio.1001179