---
OA_type: closed access
_id: '869'
abstract:
- lang: eng
  text: The impact of synonymous nucleotide substitutions on fitness in mammals remains
    controversial. Despite some indications of selective constraint, synonymous sites
    are often assumed to be neutral, and the rate of their evolution is used as a
    proxy for mutation rate. We subdivide all sites into four classes in terms of
    the mutable CpG context, nonCpG, postC, preG, and postCpreG, and compare four-fold
    synonymous sites and intron sites residing outside transposable elements. The
    distribution of the rate of evolution across all synonymous sites is trimodal.
    Rate of evolution at nonCpG synonymous sites, not preceded by C and not followed
    by G, is ∼10% below that at such intron sites. In contrast, rate of evolution
    at postCpreG synonymous sites is ∼30% above that at such intron sites. Finally,
    synonymous and intron postC and preG sites evolve at similar rates. The relationship
    between the levels of polymorphism at the corresponding synonymous and intron
    sites is very similar to that between their rates of evolution. Within every class,
    synonymous sites are occupied by G or C much more often than intron sites, whose
    nucleotide composition is consistent with neutral mutation-drift equilibrium.
    These patterns suggest that synonymous sites are under weak selection in favor
    of G and C, with the average coefficient s∼0.25/Ne∼10-5, where Ne is the effective
    population size. Such selection decelerates evolution and reduces variability
    at sites with symmetric mutation, but has the opposite effects at sites where
    the favored nucleotides are more mutable. The amino-acid composition of proteins
    dictates that many synonymous sites are CpGprone, which causes them, on average,
    to evolve faster and to be more polymorphic than intron sites. An average genotype
    carries ∼107 suboptimal nucleotides at synonymous sites, implying synergistic
    epistasis in selection against them.
acknowledgement: This research was supported in part by the Intramural Research Program
  of the NIH, National Library of Medicine.
article_processing_charge: No
article_type: original
author:
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
- first_name: Aleksey
  full_name: Ogurtsov, Aleksey
  last_name: Ogurtsov
- first_name: Alexey
  full_name: Kondrashov, Alexey
  last_name: Kondrashov
citation:
  ama: Kondrashov F, Ogurtsov A, Kondrashov A. Selection in favor of nucleotides G
    and C diversifies evolution rates and levels of polymorphism at mammalian synonymous
    sites. <i>Journal of Theoretical Biology</i>. 2006;240(4):616-626. doi:<a href="https://doi.org/10.1016/j.jtbi.2005.10.020">10.1016/j.jtbi.2005.10.020</a>
  apa: Kondrashov, F., Ogurtsov, A., &#38; Kondrashov, A. (2006). Selection in favor
    of nucleotides G and C diversifies evolution rates and levels of polymorphism
    at mammalian synonymous sites. <i>Journal of Theoretical Biology</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.jtbi.2005.10.020">https://doi.org/10.1016/j.jtbi.2005.10.020</a>
  chicago: Kondrashov, Fyodor, Aleksey Ogurtsov, and Alexey Kondrashov. “Selection
    in Favor of Nucleotides G and C Diversifies Evolution Rates and Levels of Polymorphism
    at Mammalian Synonymous Sites.” <i>Journal of Theoretical Biology</i>. Elsevier,
    2006. <a href="https://doi.org/10.1016/j.jtbi.2005.10.020">https://doi.org/10.1016/j.jtbi.2005.10.020</a>.
  ieee: F. Kondrashov, A. Ogurtsov, and A. Kondrashov, “Selection in favor of nucleotides
    G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous
    sites,” <i>Journal of Theoretical Biology</i>, vol. 240, no. 4. Elsevier, pp.
    616–626, 2006.
  ista: Kondrashov F, Ogurtsov A, Kondrashov A. 2006. Selection in favor of nucleotides
    G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous
    sites. Journal of Theoretical Biology. 240(4), 616–626.
  mla: Kondrashov, Fyodor, et al. “Selection in Favor of Nucleotides G and C Diversifies
    Evolution Rates and Levels of Polymorphism at Mammalian Synonymous Sites.” <i>Journal
    of Theoretical Biology</i>, vol. 240, no. 4, Elsevier, 2006, pp. 616–26, doi:<a
    href="https://doi.org/10.1016/j.jtbi.2005.10.020">10.1016/j.jtbi.2005.10.020</a>.
  short: F. Kondrashov, A. Ogurtsov, A. Kondrashov, Journal of Theoretical Biology
    240 (2006) 616–626.
date_created: 2018-12-11T11:48:56Z
date_published: 2006-06-21T00:00:00Z
date_updated: 2026-05-08T10:18:03Z
day: '21'
doi: 10.1016/j.jtbi.2005.10.020
extern: '1'
external_id:
  pmid:
  - '16343547'
fulldoi: https://doi.org/10.1016/j.jtbi.2005.10.020
intvolume: '       240'
issue: '4'
keyword:
- Mutation
- Selection
- Synonymous site
- Evolution
- Genetic drift
language:
- iso: eng
month: '06'
oa_version: None
page: 616 - 626
pmid: 1
publication: Journal of Theoretical Biology
publication_identifier:
  issn:
  - 1095-8541
publication_status: published
publisher: Elsevier
publist_id: '6779'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Selection in favor of nucleotides G and C diversifies evolution rates and levels
  of polymorphism at mammalian synonymous sites
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 240
year: '2006'
...