Standard Article

Evolution of Human Gene Expression Control

  1. J Lomax Boyd,
  2. Gregory A Wray

Published Online: 17 FEB 2014

DOI: 10.1002/9780470015902.a0020769.pub2



How to Cite

Boyd, J. L. and Wray, G. A. 2014. Evolution of Human Gene Expression Control. eLS. .

Author Information

  1. Duke University, Durham, North Carolina, USA

Publication History

  1. Published Online: 17 FEB 2014


The evolutionary history of our species is associated with the emergence of numerous phenotypic traits thought to be unique to humans. Comparative analysis of gene expression between human and nonhuman primates has revealed thousands of genes differentially expressed across multiple tissues. Comparative and functional genomic studies have implicated variation in cis-regulatory regions, or enhancer elements, as a major component of species-specific expression differences. Additionally, adaptive evolution between modern human populations has also been attributed to variation in cis-regulatory regions of the genome. Despite these advances, the genetic basis of most derived human traits, population-specific differences and heritable variation in gene expression remains unidentified. Gene regulation is known to proceed through the combinatorial interaction of multiple loci, acting cooperatively or redundantly, to regulate contextual gene expression in different tissues or at different times during development. The role of epistasis, the genetic interaction between loci, may, therefore, have a significant influence on the evolution of regulatory elements underlying trait difference between primate species and human populations.

Key Concepts:

  • Numerous highly conserved noncoding elements are rapidly evolving in humans and many function as tissue-specific developmental enhancers.

  • Variation in phenotypic traits, including disease susceptibility, has been mapped to noncoding, cis-regulatory loci.

  • Comparison of multiple primate genomes has enabled the identification of loci under both adaptive evolution (positive selection) and evolutionary constraint (negative selection).

  • Natural selection within protein-coding and noncoding regions of genome is not uniform but more preferentially targets certain biological categories of genes.

  • The role of epistasis in the evolution of human gene expression control is unknown for most traits but may be significant.


  • cis-regulation;
  • functional genomics;
  • human evolution;
  • gene expression;
  • polymorphism;
  • epistasis;
  • human populations;
  • enhancer;
  • natural selection