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MBE Advance Access published online on June 23, 2008
Molecular Biology and Evolution, 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 Article

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

* Corresponding author: Aoife McLysaght, Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland, Tel: +353-1-8963161. Fax: +353-1-6798558. E-mail: aoife.mclysaght{at}tcd.ie

Received for publication February 6, 2008. Revision received June 3, 2008. Accepted for publication June 3, 2008.

Unravelling the "code" of genome structure is an important goal of genomics research. Co-localization of genes in eukaryotic genomes may facilitate preservation of favourable allele combinations between epistasic loci or co-regulation 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 on 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 MHC. 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


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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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