Adaptive evolution of cis‐regulatory regions among genes dynamically expressed in the juvenile human cortex (89.8)

Abstract

The human brain excels in its capacity for phenotypic plasticity and response to experience. The objective of this study is to investigate the evolutionary history of human brain plasticity. We previously argued that genes that play a role in phenotypic plasticity should respond with a dynamic expression pattern during development, and we reported a set of 304 genes more variably expressed in the juvenile human cortex than adult (Sterner et al., 2012). Changes in how these genes are regulated among humans compared with non‐human primates may provide clues as to the genetic underpinnings of enhanced phenotypic plasticity in the developing human brain. Using publically available genomic data, our approach identified single nucleotides that are differ in humans (e.g. 1000 genomes project) compared to non‐human primates in regions that contain regulatory sequence (i.e., 2kb upstream, first intron, 5’‐ and 3’‐UTR). Thirty‐one out of 304 genes are enriched for regulatory sites that are derived and fixed in humans and also show dynamic expression in the juvenile human cortex (e.g., WAS, KLF4, C1QA, CTSH, PRODH, SERTAD1). Changes in the regulatory responses of these genes may contribute to the evolution of unique aspects of human brain development and plasticity.Grant Funding Source: Supported by NSF [BCS0827546], AAA Post‐doctoral Research Fellowship, and WSU Office VP Research