Pathway analysis of the action of natural selection on coding and non-coding genomic elements

Trabajo presentado en la Annual Meeting of the Society for Molecular Biology & Evolution (SMBE 2012), celebrada en Dublín del 23 al 26 de junio de 2012.The signature of Natural Selection may be detected not only upon coding regions of individual genes, but also in related functional elements (e.g. regulatory regions or introns) or multiple genes (e.g. functional modules or metabolic pathways). Indeed, genome-wide comparative genomics, using alignments between reference assemblies has allowed the identification of regulatory elements and functional modules bearing the signatures of adaptation and/or purifying selection in the lineages of various species, particularly humans and great apes. In the present study, we took a two-pronged approach: First, we focused on the coding regions of genes in four functional modules reported to be enriched with genes presenting signatures of different type s of selection in the human and chimpanzee lineages. These modules are complement and coagulation ca scade (with genes under positive selection), regulation of actin cytoskeleton (under purifying selection) and two KEGG pathways of common human neurodegenerative diseases, Alzheimer’s and Parkinson, with no clear trends of selection. Second, we studied regulatory regions aroun d these genes, including introns, UTRs, miRNA, lncRNA, promoters (5kb) and trailers (5kb). We have performed genomic capture and sequencing for the abov e target regions (totalling ~450 genes) in 20 chimpanzee individuals (Pan troglodytes troglodytes) so that, after SNP calling, we are able to study the signature of selection using both polymorphism and divergence da ta. By means of a combination of tests (frequency spectra and variations of the McD onald-Kreitman test) we are able to study the ralationship between ancestral and recent selective patterns and to dissect whether selection acted preferentially in conding or non-coding regions of the pathways under study.N