Neurogenetics: What Makes a Human Brain?

RESEARCH HIGHLIGHTS

NEUROGENETICS What makes a human brain? The quest to identify what makes identified include several that have several genes that have been impli- humans so different from our clos- been implicated in neuronal matura- cated in neuropsychiatric disorders est relatives, the great apes, focuses tion, differentiation and function. and seems to have at its core the largely on our brains. What has By contrast, gene expression circadian rhythm gene CLOCK. allowed us to develop such enlarged patterns in the caudate nucleus were Another contains the forkhead brains, and such intellectual ability, much more similar among the human, transcription factor FOXP2, which when compared with our primate chimpanzee and macaque brains. This is linked to speech and language cousins? A new study looks for might reflect more conserved func- functions in humans, and the genes answers in the transcriptomes — the tions for this part of the brain. that comprise this network are more patterns of mRNA expression — in Konopka et al. carried out interconnected in humans than in the brains of humans, chimpanzees further analyses on the data using chimpanzee and macaque brains. and macaques. a technique called weighted gene In an accompanying commentary, It has become increasingly clear co-expression network analysis. This Ponting and Oliver discuss these over recent years that the genome allowed the authors to define ‘mod- results and summarize some of the is not everything when it comes ules’ consisting of networks of genes difficulties in interpreting them. For to defining an animal. It is also in which expression was correlated example, the levels of mRNA (as essential to understand where, (positively or negatively) in a particu- measured in this study) do not always when and to what extent genes are lar area. There were more modules correlate with the levels of protein expressed during development and related to the frontal pole than to the expression. Despite these limitations, in the mature animal. So to look at other areas in the human brain, but Konopka et al. have expanded our what drives the differences between not in the chimpanzee or macaque understanding of gene expression primate brains, Konopka et al. used brains, and the authors interpret this patterns in the brain and shed new advanced sequencing and microarray as showing that the human frontal light on human brain evolution. techniques to measure the expression pole has greater transcriptional Rachel Jones of mRNA transcripts in three areas of complexity than the chimpanzee or the brain — the caudate nucleus, the macaque frontal poles. ORIGINAL RESEARCH PAPER Konopka, G. et al. Human-specific transcriptional networks in the hippocampus and the frontal pole. In their paper, Konopka et al. brain. Neuron 75, 601–617 (2012) The resulting transcriptome provides focus on some specific modules that FURTHER READING Ponting, C. P. & Oliver, P. L. insight into the spatial patterns of centre around genes of particular Brain, know thy transcriptome, know thyself. The resulting Neuron 75, 543–545 (2012) gene expression in these brain areas interest. One example contains transcriptome and allows comparisons between the provides three species. insight into Comparisons of the lists of genes the spatial that are expressed in each area identified genes that were differentially patterns expressed in the human brain when of gene compared with the macaque or expression chimpanzee brain, and there were more differentially expressed genes in these in the human frontal pole than in the brain areas caudate nucleus or hippocampus. and allows This is perhaps not surprising, as comparisons the human frontal cortex is the most disproportionately enlarged part of between the the brain and is thought to be respon- three species. sible for many of the functions that distinguish our cognitive skills from those of other primates. The genes CORBIS

NATURE REVIEWS | NEUROSCIENCE VOLUME 13 | OCTOBER 2012