background selection

Cai JJ, Macpherson M, Sella G & Petrov DA 2009 Pervasive hitchhiking at coding and regulatory sites in humans. PLoS Genet 5:e1000336.

  • natural selection at both coding and regulatory sites appears to affect linked neutral polymorphism
  • reducing neutral polymorphism by 6% genome-wide and by 11% in the gene-rich half of the human genome
  • consistent with the expectations of positive selection, we detect a positive correlation between levels of neutral polymorphism and recombination rate and a negative correlation between levels of nucleotide polymorphism and both functional density and functional divergence
  • we consider alternative explanations for these findings and argue that, in addition to recurrent selective sweep, only background selection (BS) (loss of neutral variants due to hitchhiking with linked deleterious mutations) can possibly generate most of these patterns
  • hitchhiking of neutral polymorphisms with linked selected variants—either due to recurrent positive selection or background selection or possibly both—appears to be a substantial force determining levels of neutral polymorphism in the human genome
  • background selection (BS) is the process of hitchhiking of neutral or weakly deleterious polymorphism with linked strongly deleterious polymorphisms
  • the positive correlation between neutral polymorphism and recombination rate is due in part to BS
  • BS is likely to contribute to the negative correlation between levels of neutral polymorphism and functional density as well
  • BS could contribute to the negative correlation between levels of neutral polymorphism and functional divergence as well
  • it is less clear whether BS could generate the negative correlation between the levels of neutral polymorphism and functional divergence after controlling for levels of functional density
  • what is the relative importance of RSS and BS?
  • can we estimate parameters of adaptive evolution in the presence of BS?
  • the availability of whole genome sequences in a large number of humans may provide the necessary data to answer these questions