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Strong purifying selection at synonymous sites in D. melanogaster

Lawrie, David S ; Messer, Philipp W ; Hershberg, Ruth ; Petrov, Dmitri A Plotkin, Joshua B.

PLoS genetics, 2013-05, Vol.9 (5), p.e1003527 [Periódico revisado por pares]

United States: Public Library of Science

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  • Título:
    Strong purifying selection at synonymous sites in D. melanogaster
  • Autor: Lawrie, David S ; Messer, Philipp W ; Hershberg, Ruth ; Petrov, Dmitri A
  • Plotkin, Joshua B.
  • Assuntos: Amino Acid Substitution - genetics ; Animals ; Bias ; Biology ; Drosophila ; Drosophila melanogaster - genetics ; Evolution, Molecular ; Gene Expression ; Genetic aspects ; Genetic Drift ; Genetic polymorphisms ; Genetics ; Health aspects ; Humans ; Mutation ; Phylogeny ; Physiological aspects ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Proteins ; Selection, Genetic - genetics
  • É parte de: PLoS genetics, 2013-05, Vol.9 (5), p.e1003527
  • Notas: Analyzed the data: DSL PWM RH DAP. Wrote the paper: DSL PWM RH DAP. Conceived and designed methodologies: DSL PWM RH DAP. Designed and wrote software used in analysis: DSL.
    The authors have declared that no competing interests exist.
  • Descrição: Synonymous sites are generally assumed to be subject to weak selective constraint. For this reason, they are often neglected as a possible source of important functional variation. We use site frequency spectra from deep population sequencing data to show that, contrary to this expectation, 22% of four-fold synonymous (4D) sites in Drosophila melanogaster evolve under very strong selective constraint while few, if any, appear to be under weak constraint. Linking polymorphism with divergence data, we further find that the fraction of synonymous sites exposed to strong purifying selection is higher for those positions that show slower evolution on the Drosophila phylogeny. The function underlying the inferred strong constraint appears to be separate from splicing enhancers, nucleosome positioning, and the translational optimization generating canonical codon bias. The fraction of synonymous sites under strong constraint within a gene correlates well with gene expression, particularly in the mid-late embryo, pupae, and adult developmental stages. Genes enriched in strongly constrained synonymous sites tend to be particularly functionally important and are often involved in key developmental pathways. Given that the observed widespread constraint acting on synonymous sites is likely not limited to Drosophila, the role of synonymous sites in genetic disease and adaptation should be reevaluated.
  • Editor: United States: Public Library of Science
  • Idioma: Inglês
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