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Related Experiment Videos

The case for selection at CCR5-Delta32.

Pardis C Sabeti1, Emily Walsh, Steve F Schaffner

  • 1Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. pardis@broad.mit.edu

Plos Biology
|October 27, 2005
PubMed
Summary
This summary is machine-generated.

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The CCR5-Delta32 allele, offering HIV resistance, likely emerged over 5,000 years ago, not recently as previously thought. Its genetic pattern suggests neutral evolution rather than strong selective pressures like historical plagues.

Area of Science:

  • Human genetics
  • Evolutionary biology
  • Infectious disease resistance

Background:

  • The CCR5-Delta32 allele provides significant protection against HIV infection.
  • Previous research suggested this allele arose recently (within 1,000 years) and was driven by strong positive selection due to historical epidemics.

Purpose of the Study:

  • To re-evaluate the evolutionary origins and selection pressures of the CCR5-Delta32 allele using updated genetic data.
  • To determine if the genetic variation pattern at CCR5 is exceptional or consistent with neutral evolution.

Main Methods:

  • Analysis of genetic variation patterns at the CCR5 locus using dense genetic maps.
  • Comparison of CCR5-Delta32 genetic patterns with genome-wide control data.
  • Estimation of the allele's age of origin.

Related Experiment Videos

Main Results:

  • The genetic variation pattern at CCR5-Delta32 is not statistically exceptional compared to other genomic loci.
  • New estimates suggest the CCR5-Delta32 allele originated more than 5,000 years ago.
  • The observed genetic patterns are consistent with neutral evolutionary processes.

Conclusions:

  • The evolutionary history of CCR5-Delta32 appears to be driven by neutral evolution, not recent strong selection from epidemics.
  • While some selection cannot be entirely ruled out, the data challenges previous hypotheses about its rapid rise in frequency.
  • Findings have implications for identifying signatures of positive selection in the human genome.