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 processes(1-5), despite pronounced differences between humans and chimpanzees in behavior, cognition and diet(6-8). It may be that most such differences are due to changes in gene regulation rather than protein structure(9). 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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