---
OA_type: closed access
_id: '847'
abstract:
- lang: eng
  text: The accumulation of genome-wide information on single nucleotide polymorphisms
    in humans provides an unprecedented opportunity to detect the evolutionary forces
    responsible for heterogeneity of the level of genetic variability across loci.
    Previous studies have shown that history of recombination events has produced
    long haplotype blocks in the human genome, which contribute to this heterogeneity.
    Other factors, however, such as natural selection or the heterogeneity of mutation
    rates across loci, may also lead to heterogeneity of genetic variability. We compared
    synonymous and non-synonymous variability within human genes with their divergence
    from murine orthologs. We separately analyzed the non-synonymous variants predicted
    to damage protein structure or function and the variants predicted to be functionally
    benign. The predictions were based on comparative sequence analysis and, in some
    cases, on the analysis of protein structure. A strong correlation between non-synonymous,
    benign variability and non-synonymous human-mouse divergence suggests that selection
    played an important role in shaping the pattern of variability in coding regions
    of human genes. However, the lack of correlation between deleterious variability
    and evolutionary divergence shows that a substantial proportion of the observed
    non-synonymous single-nucleotide polymorphisms reduces fitness and never reaches
    fixation. Evolutionary and medical implications of the impact of selection on
    human polymorphisms are discussed.
acknowledgement: We are grateful to Alexey Kondrashov and Alison Wellman for the careful
  reading of the manuscript and providing us with their valuable comments.
article_processing_charge: No
article_type: original
author:
- first_name: Shamil
  full_name: Sunyaev, Shamil
  last_name: Sunyaev
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
- first_name: Peer
  full_name: Bork, Peer
  last_name: Bork
- first_name: Vasily
  full_name: Ramensky, Vasily
  last_name: Ramensky
citation:
  ama: Sunyaev S, Kondrashov F, Bork P, Ramensky V. Impact of selection, mutation
    rate and genetic drift on human genetic variation. <i>Human Molecular Genetics</i>.
    2003;12(24):3325-3330. doi:<a href="https://doi.org/10.1093/hmg/ddg359">10.1093/hmg/ddg359</a>
  apa: Sunyaev, S., Kondrashov, F., Bork, P., &#38; Ramensky, V. (2003). Impact of
    selection, mutation rate and genetic drift on human genetic variation. <i>Human
    Molecular Genetics</i>. Oxford Academic. <a href="https://doi.org/10.1093/hmg/ddg359">https://doi.org/10.1093/hmg/ddg359</a>
  chicago: Sunyaev, Shamil, Fyodor Kondrashov, Peer Bork, and Vasily Ramensky. “Impact
    of Selection, Mutation Rate and Genetic Drift on Human Genetic Variation.” <i>Human
    Molecular Genetics</i>. Oxford Academic, 2003. <a href="https://doi.org/10.1093/hmg/ddg359">https://doi.org/10.1093/hmg/ddg359</a>.
  ieee: S. Sunyaev, F. Kondrashov, P. Bork, and V. Ramensky, “Impact of selection,
    mutation rate and genetic drift on human genetic variation,” <i>Human Molecular
    Genetics</i>, vol. 12, no. 24. Oxford Academic, pp. 3325–3330, 2003.
  ista: Sunyaev S, Kondrashov F, Bork P, Ramensky V. 2003. Impact of selection, mutation
    rate and genetic drift on human genetic variation. Human Molecular Genetics. 12(24),
    3325–3330.
  mla: Sunyaev, Shamil, et al. “Impact of Selection, Mutation Rate and Genetic Drift
    on Human Genetic Variation.” <i>Human Molecular Genetics</i>, vol. 12, no. 24,
    Oxford Academic, 2003, pp. 3325–30, doi:<a href="https://doi.org/10.1093/hmg/ddg359">10.1093/hmg/ddg359</a>.
  short: S. Sunyaev, F. Kondrashov, P. Bork, V. Ramensky, Human Molecular Genetics
    12 (2003) 3325–3330.
date_created: 2018-12-11T11:48:49Z
date_published: 2003-12-15T00:00:00Z
date_updated: 2026-05-28T14:13:45Z
day: '15'
doi: 10.1093/hmg/ddg359
extern: '1'
external_id:
  pmid:
  - '14570704 '
intvolume: '        12'
issue: '24'
language:
- iso: eng
month: '12'
oa_version: None
page: 3325 - 3330
pmid: 1
publication: Human Molecular Genetics
publication_identifier:
  eissn:
  - 1460-2083
  issn:
  - 0964-6906
publication_status: published
publisher: Oxford Academic
publist_id: '6803'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Impact of selection, mutation rate and genetic drift on human genetic variation
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 12
year: '2003'
...