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Related Experiment Videos

Chromatin structure and evolution in the human genome.

James G D Prendergast1, Harry Campbell, Nick Gilbert

  • 1Colon Cancer Genetics Group, Division of Oncology, University of Edinburgh, Western General Hospital, Edinburgh, UK. James.Prendergast@hgu.mrc.ac.uk

BMC Evolutionary Biology
|May 11, 2007
PubMed
Summary
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Genome chromatin structure influences mutation rates. Open chromatin shows lower mutation rates, while closed chromatin exhibits higher rates, impacting evolutionary studies.

Area of Science:

  • Genomics and Evolutionary Biology
  • Human Genetics
  • Chromatin Structure and Function

Background:

  • Evolutionary rates vary across the human genome, with neighboring genes often showing similar divergence and selection.
  • Higher-order chromosome organization is hypothesized to explain these patterns, but robust data linking chromatin structure to evolutionary rates was lacking.

Purpose of the Study:

  • To investigate the global association between human chromatin structure (open vs. closed) and genome-wide divergence and selection for the first time.
  • To analyze how chromatin organization impacts mutation rates and selective pressures across different genomic regions.

Main Methods:

  • Utilized genome-wide analysis of open and closed human chromatin structures.
  • Examined synonymous site divergence (dS) at non-CpG sites and other mutation measures (intergenic, intronic, repeat divergence, SNP density).

Related Experiment Videos

  • Analyzed human-chimpanzee divergence across intron-exon boundaries and investigated the role of ncRNA genes in closed chromatin.

    • Main Results:

    • Paradoxically, synonymous site divergence (dS) at non-CpG sites is highest in open chromatin, driven by increased transitions.
    • Other mutation measures and SNP density are highest in closed chromatin regions.
    • Genes in closed chromatin show lower fourfold degenerate site divergence compared to neighboring introns/intergenic regions, indicating stronger selection.

    Conclusions:

    • Non-CpG mutation rates are lowest in open chromatin and highest in closed chromatin.
    • Closed chromatin may have higher background mutation rates, potentially due to increased DNA damage or reduced repair.
    • Synonymous site divergence (dS) is an unreliable measure of mutation rates in closed chromatin due to strong selective pressures.