Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts

Autor(es)

Ramalho, Rodrigo F. ^{[1, 2]} ; Gelfman, Sahar ^[3] ; de Souza, Jorge E. ^[2] ; Ast, Gil ^[3] ; de Souza, Sandro J. ^{[4, 2]} ; Meyer, Diogo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-05508900 Sao Paulo - Brazil

^[2] Inst Bioinformat & Biotecnol, Ribeirao Preto, SP - Brazil

^[3] Tel Aviv Univ, Sackler Fac Med, Dept Human Mol Genet & Biochem, IL-69978 Ramat Aviv - Israel

^[4] Univ Fed Rio Grande do Norte, Inst Cerebro, BR-59072970 Natal, RN - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Molecular Evolution; v. 76, n. 4, p. 228-239, APR 2013.
• Citações Web of Science: 3

Resumo

Despite evidence that at the interspecific scale, exonic splicing silencers (ESSs) are under negative selection in constitutive exons, little is known about the effects of slightly deleterious polymorphisms on these splicing regulators. Through the application of a modified version of the McDonald-Kreitman test, we compared the normalized proportions of human polymorphisms and human/rhesus substitutions affecting exonic splicing regulators (ESRs) on sequences of constitutive and alternative exons. Our results show a depletion of substitutions and an enrichment of SNPs associated with ESS gain in constitutive exons. Moreover, we show that this evolutionary pattern is also present in a set of ESRs previously involved in the transition from constitutive to skipped exons in the mammalian lineage. The similarity between these two sets of ESRs suggests that the transition from constitutive to skipped exons in mammals is more frequently associated with the inhibition than with the promotion of splicing signals. This is in accordance with the hypothesis of a constitutive origin of exon skipping and corroborates previous findings about the antagonistic role of certain exonic splicing enhancers. (AU)

• Processo FAPESP: 09/09127-8 - Evolução molecular e genética de populações de genes HLA
• Beneficiário: Diogo Meyer
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/59721-8 - EFEITOS DA SELECAO NATURAL EM ATIVADORES DE SPLICING EXONICO (ESEs) DO GENOMA HUMANO
• Beneficiário: Rodrigo Fernandes Ramalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado