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synonymous mutations not neutral?

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  • Marc Verhaegen
    PNAS 103:6940-5 Weak selection and recent mutational changes influence polymorphic synonymous mutations in humans Josep M Comeron 2006 Recent large-scale
    Message 1 of 1 , May 2, 2006
      PNAS 103:6940-5
      Weak selection and recent mutational changes influence polymorphic
      synonymous mutations in humans
      Josep M Comeron 2006

      Recent large-scale genomic and evolutionary studies have revealed the small
      but detectable signature of weak selection on synonymous mutations during
      mammalian evolution, likely acting at the level of translational efficacy
      (i.e., translational selection). To investigate whether weak selection, and
      translational selection in particular, plays any role in shaping the fate of
      synonymous mutations that are present today in human populations, we studied
      genetic variation at the polymorphic level and patterns of evolution in the
      human lineage after human-chimpanzee separation. We find evidence that
      neutral mechanisms are influencing the frequency of polymorphic mutations in
      humans. Our results suggest a recent increase in mutational tendencies
      toward AT, observed in all isochores, that is responsible for AT mutations
      segregating at lower frequencies than GC mutations. In all, however, changes
      in mutational tendencies and other neutral scenarios are not sufficient to
      explain a difference between synonymous and noncoding mutations or a
      difference between synonymous mutations potentially advantageous or
      deleterious under a translational selection model. Furthermore, several
      estimates of selection intensity on synonymous mutations all suggest a
      detectable influence of weak selection acting at the level of translational
      selection. Thus, random genetic drift, recent changes in mutational
      tendencies, and weak selection influence the fate of synonymous mutations
      that are present today as polymorphisms. All of these features, neutral and
      selective, should be taken into account in evolutionary analyses that often
      assume constancy of mutational tendencies and complete neutrality of
      synonymous mutations.
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