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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 6
[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
Total Affiliations: 4
Document type: Journal article
Source: Journal of Molecular Evolution; v. 76, n. 4, p. 228-239, APR 2013.
Web of Science Citations: 3

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)

FAPESP's process: 09/09127-8 - Molecular evolution and population genetics of HLA genes
Grantee:Diogo Meyer
Support type: Regular Research Grants