Surveys of protein-coding sequences for evidence of positive selection in humans or chimpanzees have flagged only a few genes known to function in neural or nutritional processes1,2,3,4,5, despite pronounced differences between humans and chimpanzees in behavior, cognition and diet6,7,8. It may be that most such differences are due to changes in gene regulation rather than protein structure9. Here, we present the first survey of promoter (5′-flanking) regions, which are rich in cis-regulatory sequences, for evidence of positive selection in humans. Our results indicate that positive selection has targeted the regulation of many genes known to be involved in neural development and function, both in the brain and elsewhere in the nervous system, and in nutrition, particularly in glucose metabolism.
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We thank J. Pavisic and T. Severson for assistance with gene annotations; G. Barber, M. Diekhans, W. Kent, S. Kosakovsky Pond and W. Miller for advice about their software; F. Hsu, K. Rosenbloom and A. Zweig for advice about UCSC resources and J. Horvath, J. Pritchard, M. Turelli, H. Willard and members of the G. Wray laboratory for comments on the manuscript. Most of the computations were performed on the Duke Shared Cluster Resource, which is maintained by the Duke Center for Computational Science, Engineering and Medicine. This research was supported by the Duke Institute for Genome Sciences and Policy and a US National Science Foundation Postdoctoral Fellowship in Biological Informatics to R.H. (grant number 0434655).
The authors declare no competing financial interests.
A fuller presentation of our models. (XLS 38 kb)
Basic results, human lineage, passing cutoffs. (XLS 2487 kb)
Basic results, human lineage, failing cutoffs. (XLS 1608 kb)
Basic results, chimpanzee lineage, passing cutoffs. (XLS 2480 kb)
Basic results, chimpanzee lineage, failing cutoffs. (XLS 1599 kb)
Further analyses of PANTHER biological process categories. (XLS 59 kb)
Supplementary Discussion (PDF 472 kb)
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Haygood, R., Fedrigo, O., Hanson, B. et al. Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution. Nat Genet 39, 1140–1144 (2007). https://doi.org/10.1038/ng2104
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