1. Department of Genetics and Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06510, USA
2. Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
3. Department of Statistics and Program in Biostatistics, University of California, Berkeley, California 94720, USA
4. †Present address: Department of Human Genetics, University of Chicago, Chicago, Illinois 60605, USA

Correspondence to: Yoav Gilad^1,4Kevin P. White¹ Correspondence and requests for materials should be addressed to Y.G. (Email: gilad@uchicago.edu) or K.P.W. (Email: kevin.white@yale.edu).

Abstract

Although it has been hypothesized for thirty years that many human adaptations are likely to be due to changes in gene regulation¹, almost nothing is known about the modes of natural selection acting on regulation in primates. Here we identify a set of genes for which expression is evolving under natural selection. We use a new multi-species complementary DNA array to compare steady-state messenger RNA levels in liver tissues within and between humans, chimpanzees, orangutans and rhesus macaques. Using estimates from a linear mixed model, we identify a set of genes for which expression levels have remained constant across the entire phylogeny (70 million years), and are therefore likely to be under stabilizing selection. Among the top candidates are five genes with expression levels that have previously been shown to be altered in liver carcinoma. We also find a number of genes with similar expression levels among non-human primates but significantly elevated or reduced expression in the human lineage, features that point to the action of directional selection. Among the gene set with a human-specific increase in expression, there is an excess of transcription factors; the same is not true for genes with increased expression in chimpanzee.

1. Department of Genetics and Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06510, USA
2. Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
3. Department of Statistics and Program in Biostatistics, University of California, Berkeley, California 94720, USA
4. †Present address: Department of Human Genetics, University of Chicago, Chicago, Illinois 60605, USA

Correspondence to: Yoav Gilad^1,4Kevin P. White¹ Correspondence and requests for materials should be addressed to Y.G. (Email: gilad@uchicago.edu) or K.P.W. (Email: kevin.white@yale.edu).

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