High genomic deleterious mutation rates in hominids

Nature. 1999 Jan 28;397(6717):344-7. doi: 10.1038/16915.


It has been suggested that humans may suffer a high genomic deleterious mutation rate. Here we test this hypothesis by applying a variant of a molecular approach to estimate the deleterious mutation rate in hominids from the level of selective constraint in DNA sequences. Under conservative assumptions, we estimate that an average of 4.2 amino-acid-altering mutations per diploid per generation have occurred in the human lineage since humans separated from chimpanzees. Of these mutations, we estimate that at least 38% have been eliminated by natural selection, indicating that there have been more than 1.6 new deleterious mutations per diploid genome per generation. Thus, the deleterious mutation rate specific to protein-coding sequences alone is close to the upper limit tolerable by a species such as humans that has a low reproductive rate, indicating that the effects of deleterious mutations may have combined synergistically. Furthermore, the level of selective constraint in hominid protein-coding sequences is atypically low. A large number of slightly deleterious mutations may therefore have become fixed in hominid lineages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Evolution, Molecular
  • Gene Frequency
  • Hominidae / genetics*
  • Humans
  • Mutation*
  • Pan troglodytes / genetics
  • Proteins / genetics
  • Reproduction


  • Proteins