Evidence for widespread positive and purifying selection across the european rabbit (oryctolagus cuniculus) genome

Miguel Carneiro, Frank W. Albert, José Melo-Ferreira, Nicolas Galtier, Philippe Gayral, Jose A. Blanco-Aguiar, Rafael Villafuerte, Michael W. Nachman, Nuno Ferrand

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60 Scopus citations


The nearly neutral theory of molecular evolution predicts that the efficacy of both positive and purifying selection is a function of the long-term effective population size (Ne) of a species. Under this theory, the efficacy of natural selection should increase with Ne. Here, we tested this simple prediction by surveying ∼1.5 to 1.8 Mb of protein coding sequence in the two subspecies of the European rabbit (Oryctolagus cuniculus algirus and O. c. cuniculus), a mammal species characterized by high levels of nucleotide diversity and Ne estimates for each subspecies on the order of 1 × 10. When the segregation of slightly deleterious mutations and demographic effects were taken into account, we inferred that >60 of amino acid substitutions on the autosomes were driven to fixation by positive selection. Moreover, we inferred that a small fraction of new amino acid mutations (<4) are effectively neutral (defined as 0 < Nes < 1) and that this fraction was negatively correlated with a gene's expression level. Consistent with models of recurrent adaptive evolution, we detected a negative correlation between levels of synonymous site polymorphism and the rate of protein evolution, although the correlation was weak and nonsignificant. No systematic X chromosome-autosome difference was found in the efficacy of selection. For example, the proportion of adaptive substitutions was significantly higher on the X chromosome compared with the autosomes in O. c. algirus but not in O. c. cuniculus. Our findings support widespread positive and purifying selection in rabbits and add to a growing list of examples suggesting that differences in Ne among taxa play a substantial role in determining rates and patterns of protein evolution.

Original languageEnglish (US)
Pages (from-to)1837-1849
Number of pages13
JournalMolecular biology and evolution
Issue number7
StatePublished - Jul 2012


  • McDonald-Kreitman test
  • distribution of fitness effects
  • effective population size
  • nearly neutral theory
  • proportion of adaptive substitutions
  • transcriptome


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