Genome Scale Adaptation by Selection on Functional Modules.

F SERRA, L ARBIZA, J DOPAZO AND H DOPAZO

Valencia España

Congreso; 2do Congreso de la Sociedad Española de Biología Evolutiva; 2009

Sociedad Española de Biología Evolutiva

Genome Scale Adaptation by Selection on Functional Modules François Serra1, Leonardo Arbiza1,3, Joaquín Dopazo2 & Hernán Dopazo1 1Comparative Genomics Unit. 2Functional Genomics Unit. Bioinformatics & Genomics Department. Centro de Investigacion Principe Felipe. 3 Bioinformatics and Molecular Evolution Laoratory. Facultad de Biologia. Vigo. Spain The current paradigm for large scale analyses of adaptation is based on testing the deviation from the expected neutral evolutionary rates for each individual gene in the study. This approach, that implicitly assumes independence among the genes, has failed, however, to identify modules of functionally-related genes that are significantly under positive selection. The search for signatures of selection among groups of related species has partly overcome this problem. Nevertheless, adaptive differences between individual species cannot be tested with this strategy. Here we introduce the Gene Set Selection Analysis (GSSA), a gene-set based approach to test for adaptation in the context of evolutionary genomics in mammals and Drosophila species. Gene-set analysis across lists of genes ranked by different evolutionary rate parameters (dN, dS, dN/dS) was computed. A significant asymmetric distribution of gene sets towards the extremes of a list of ranked genes was obtained by means of a segmentation test. This test consists of the sequential application of a Fisher's exact test over the contingency tables formed with the two sides of different partitions made on the ordered list of genes. Tests were further corrected for multiple adjustment effects. Its application to the complete genomes of four mammals and five Drosophila species identified a high number of gene sets, conforming modules of functionally-related genes, with significant associations to fast and slow rates of evolution in different species. Positively selected genes were found almost evenly distributed in functional modules showing significantly high and low dN/dS ratios within the genomes, questioning their role as individual actors in the adaptive evolution of species. On the other hand, the extensive and strong association of functional modules to evolutionary rates suggests that selection might be operating by means of slight but coordinated changes within them. With the testing strategy proposed here, based on the viewpoints of systems biology we have increased the statistical power for the evolutionary analysis of individual genomes in orders of magnitude. As a corollary, our results suggest that, beyond individual genes, functional modules should be considered an important target of selection. 1. Arbiza, L., J. Dopazo, and H. Dopazo. 2006. Positive selection, relaxation, and acceleration in the evolution of the human and chimp genome. PLoS Comput Biol 2:e38. 2. Al-Shahrour, F., L. Arbiza, H. Dopazo, J. Huerta-Cepas, P. Minguez, D. Montaner, and J. Dopazo. 2007. From genes to functional classes in the study of biological systems. BMC Bioinformatics 8:114. 3. Clark, A. G.M. B. Eisen D. R. Smith C. M., et al (417 co-authors). 2007. Evolution of genes and genomes on the Drosophila phylogeny. Nature 450:203-218. 4. Kosiol, C., T. Vinar, R. R. da Fonseca, M. J. Hubisz, C. D. Bustamante, R. Nielsen, and A. Siepel. 2008. Patterns of positive selection in six Mammalian genomes. PLoS Genet 4:e1000144. 5. Wilkins, A. S. 2007. Between "design" and "bricolage": genetic networks, levels of selection, and adaptive evolution. Proc Natl Acad Sci U S A 104 Suppl 1:8590-8596.