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                       BIOINFORMATICS COLLOQUIUM
                    School of Computational Sciences
                        George Mason University
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                Natural selection and self-organization
         in the evolution of the human gene expression network

                           I. King Jordan
                                NCBI

                        Thursday, April 8, 2004
                               4:30 pm
                Verizon Auditorium, Prince William Campus

The role of natural selection in evolution 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.  The topology of a human gene
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 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 gene
expression profile divergence between human and mouse.  This suggests
that distinct modes of natural selection may govern sequence versus
expression divergence, and I will propose a model, based on convergent
evolution of gene expression patterns, for how natural selection may
influence gene expression divergence.

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Refreshments are served at 4:00 pm.  Find the schedule and directions at
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