MBE Advance Access published online on July 28, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh222
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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1 National Center for Biotechnology Information National Institutes of Health Bethesda, MD 20894
* To whom correspondence should be addressed. E-mail: koonin{at}ncbi.nlm.nih.gov.
The role of natural selection in biology is well appreciated; recently, however, a critical role for physical principles of network self-organization in biological systems has been revealed. Here we employ a systems level view of genome-scale sequence and expression data to examine the interplay between these two sources of order, natural selection and physical self-organization, in the evolution of human gene regulation. The topology of a human gene co-expression network, derived from tissue-specific expression profiles, shows scale-free properties that imply evolutionary self-organization via preferential node attachment. Genes with numerous co-expressed partners (the hubs of the co-expression network) evolve more slowly on average than genes with fewer coexpressed partners, and genes that are co-expressed show similar rates of evolution. Thus, the strength of selective constraints on gene sequences is affected by the topology of the gene co-expression network. This connection is strong for the coding regions and 3'-untranslated regions (UTRs), but the 5'-UTRs appear to evolve under a different regime. Surprisingly, we found no connection between the rate of gene sequence divergence and the extent of gene expression profile divergence between human and mouse. This suggests that distinct modes of natural selection might govern sequence versus expression divergence, and we propose a model, based on rapid, adaptation-driven divergence and convergent evolution of gene expression patterns, for how natural selection could influence gene expression divergence.
Original Article
Conservation and Co-Evolution in the Scale-Free Human Gene Coexpression Network
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