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MBE Advance Access originally published online on June 23, 2008
Molecular Biology and Evolution 2008 25(9):1855-1862; doi:10.1093/molbev/msn137
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© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

Interacting Gene Clusters and the Evolution of the Vertebrate Immune System

Takashi Makino and Aoife McLysaght

Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland

E-mail: aoife.mclysaght{at}tcd.ie.

Accepted for publication June 3, 2008.

Unraveling the "code" of genome structure is an important goal of genomics research. Colocalization of genes in eukaryotic genomes may facilitate preservation of favorable allele combinations between epistasic loci or coregulation of functionally related genes. However, the presence of interacting gene clusters in the human genome has remained unclear. We systematically searched the human genome for evidence of closely linked genes whose protein products interact. We find 83 pairs of interacting genes that are located within 1 Mbp in the human genome or 37 if we exclude hub proteins. This number of interacting gene clusters is significantly more than expected by chance and is not the result of tandem duplications. Furthermore, we find that these clusters are significantly more conserved across vertebrate (but not chordate) genomes than other pairs of genes located within 1 Mbp in the human genome. In many cases, the genes are both present but not clustered in older vertebrate lineages. These results suggest gene cluster creation along the human lineage. These clusters are not enriched for housekeeping genes, but we find a significant contribution from genes involved in "response to stimulus." Many of these genes are involved in the immune response, including, but not limited to, known clusters such as the major histocompatibility complex. That these clusters were formed contemporaneously with the origin of adaptive immunity within the vertebrate lineage suggests that novel evolutionary and regulatory constraints were associated with the operation of the immune system.

Key Words: protein–protein interaction • gene cluster • vertebrate evolution • comparative genomics

William Martin, Associate Editor


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Home page
 Mol Biol EvolHome page
T. Makino and A. McLysaght
Interacting Gene Clusters and the Evolution of the Vertebrate Immune System
Mol. Biol. Evol., December 1, 2008; 25(12): 2771 - 2771.
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