Variation in the ratio of nucleotide substitution and indel rates across genomes in mammals and bacteria

Jian Qun Chen, Ying Wu, Haiwang Yang, Joy Bergelson, Martin Kreitman, Dacheng Tian

Research output: Contribution to journalArticlepeer-review


Rates of nucleotide substitution and insertion/deletion (indel) are known to vary across the functional components of a genome. Little attention has been paid, however, to the quantitative relationship between the two. Here we investigate the ratio of nucleotide substitutions to indels (S/I) in different regions of 4 primates, 70 bacteria, and 8 other genomes. We find that the ratio differs at 5.4-times between coding and noncoding, 3.3-times between conserved and less conserved coding sequences, and 1.46-times between nonrepeat and repeat regions. The S/I ratio is also positively correlated with the level of divergence between the genomes compared. Our results suggest that the S/I ratio may reflect differences in the efficacy of selection against indels. Due to the sensitivity of indel density in different regions, this ratio varies over a much larger range. With the recent discovery suggesting that indels act as local enhancers of mutation in surrounding sequences, nucleotide substitution rates are expected to be accelerated in regions of low constraint, where indels tend to accumulate, but will otherwise be modulated in proportion to the level of a sequence's functional constraint. Indels, therefore, may play a nontrivial role in controlling differences in genetic variation and divergence across functional regions of a genome.

Original languageEnglish (US)
Pages (from-to)1523-1531
Number of pages9
JournalMolecular Biology and Evolution
Issue number7
StatePublished - Jul 2009


  • Divergence
  • Evolutionary rate
  • Insertion/deletion
  • SNP

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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