Positive selection in the human protein-protein interaction network

LUISI, PIERRE; DAVID ALVAREZ-PONCE; MARC PYBUS; MARIO A. FARES; HAFID LAAYOUNI; JAUME BERTRANPETIT

Barcelona

Jornada; XIII Jornada de Biologia Evolutiva; 2013

Societat Catalana Biología

Genes are subject to disparate selective pressures: they evolve under different strengths of purifying selection and aredifferently affected by positive selection. However, the biological mechanisms underlying such differences have notbeen fully understood yet. While most of the studies focused on describing the factors that make a protein more or lessconstrained in its evolution, the determinants of the impact of positive selection are to be discovered. Genes andproteins often function as parts of rather complex networks of interacting molecules. Therefore, understandingevolutionary forces acting on individual genes will likely benefit from considering their position in such systems.Several lines of evidence indicate that the strength of purifying selection acting on genes is affected by their relativeposition in molecular networks while much less is known for positive selection. Nevertheless, some observationssuggest that the impact of positive selection on genes is also affected by the position of their encoded proteins inmolecular networks. Analysis of a few individual pathways suggests that positive selection preferentially targets genesthat exert a high degree of control over the overall behaviour of the pathway, i.e. at ?privileged? positions. On theother hand, it has been found that genes that have evolved under positive selection since the human-chimp splittended to encode proteins acting at the periphery of the human Protein Interaction Network (PIN). This analysis,however, relied only on the human genome and on the at the time incomplete chimpanzee genome, which limited thepower of positive selection inferences. The current availability of genomic data (including the complete genomes ofseveral mammals, plus 1000 human genomes) allows to infer the action of positive selection with an unprecedentedpower. In agreement with previous results, we observed that purifying selection act at the core of the PIN while genesaffected by ancient positive selection (as inferred from comparison of 10 mammalian genomes) tend to act at itsperiphery. However, the opposite trend was observed for positive selection acting on human populations: signatures ofrecent positive selection are more likely to be observed for genes acting at the centre of the human PIN.