Evolutionary origin and maintenance of coexpressed gene clusters in mammals

Mol Biol Evol. 2006 Sep;23(9):1715-23. doi: 10.1093/molbev/msl034. Epub 2006 Jun 6.


Gene order is not random with regard to gene expression in mammals: coexpressed genes, and in particular housekeeping genes, are clustered along chromosomes more often than expected by chance. To understand the origin of these clusters and to quantify the impact of this phenomenon on genome organization, we analyzed clusters of coexpressed genes in the human and mouse genomes. We show that neighboring genes experience continuous concerted expression changes during evolution, which leads to the formation of coexpressed gene clusters. The pattern of expression within these clusters evolves more slowly than the genomic average. Moreover, by studying gene order evolution, we show that some clusters are maintained by natural selection and, therefore, have a functional significance. However, we also demonstrate that some coexpressed gene clusters are the result of neutral coevolution effects, as illustrated by the clustering of genes escaping inactivation on the X chromosome. Moreover, we show that, although statistically significant, constraints on gene orders have a limited impact on mammalian genome organization, affecting only 3-5% of the pool of human and murine genes. It had been hypothesized that coexpressed gene clusters might correspond to large chromatin domains. In contradiction, we find that most of these clusters contain only 2 genes whose coexpression may be due to transcriptional read-through or the activity of bidirectional promoters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomes, Human, X
  • Chromosomes, Human, Y
  • Cluster Analysis
  • Databases, Protein
  • Evolution, Molecular*
  • Gene Expression Regulation*
  • Gene Order*
  • Genome
  • Genome, Human
  • Humans
  • Mice
  • Multigene Family
  • Selection, Genetic*
  • Transcription, Genetic