Natural selection & self-organization in the evolution of the human gene 
expression network

The significance of natural selection in biology is well appreciated, and 
recently a critical role for physical principles of network self-organization in 
biological systems has also been revealed.  I will describe an integrated 
analysis of genome-scale sequence and expression data that was used to examine 
the interplay between these two sources of order, natural selection and physical 
self-organization, in the evolution of human gene regulation.  Human gene 
expression profiles were used to reconstruct a network of co-expressed genes.  
The topology of the human gene co-expression network shows scale-free 
properties, implying 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 co-
expressed 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 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 
expression profile divergence between human and mouse.