Abstract
The human brain differs from that of other primates, but the genetic basis of these differences remains unclear. We investigated the evolutionary pressures acting on almost all human protein-coding genes (N=11,667; 1:1 orthologs in primates) on the basis of their divergence from those of early hominins, such as Neanderthals, and non-human primates. We confirm that genes encoding brain-related proteins are among the most strongly conserved protein-coding genes in the human genome. Combining our evolutionary pressure metrics for the protein-coding genome with recent datasets, we found that this conservation applied to genes functionally associated with the synapse and expressed in brain structures such as the prefrontal cortex and the cerebellum. Conversely, several of the protein-coding genes that diverge most in hominins relative to other primates are associated with brain-associated diseases, such as micro/macrocephaly, dyslexia, and autism. We also showed that cerebellum granule neurons express a set of divergent protein-coding genes that may have contributed to the emergence of fine motor skills and social cognition in humans. This resource is available from http://neanderthal.pasteur.fr and can be used to estimate evolutionary constraints acting on a set of genes and to explore their relative contributions to human traits.
Footnotes
Proofread and polished once again, with added LMD Allen Brain dataset and the Introgression analyses now completely in the Supplementary Information.
