Monday, June 19, 2006

The "HIV resistance mutation" might be very old

This month's Trends in Genetics has an update on the story of CCR5-delta32, a human mutation present at high frequency in Europeans and Western Asians but rare outside this region. People who are homozygous for this mutation are resistant to infection by HIV. It has been thought that the allele has been under positive selection, that is, that it has improved the survival of people carrying it, long before HIV was around, and might have therefore have conferred resistance to some other epidemic such as plague or smallpox.

The update talks about data that CCR5-delta32 might not have been historically under such strong selection as previously thought. The main new argument is that the mutation has been found in Bronze age bones, which means it has been around for a long time and might not be ramping upward in frequency over time as would be expected for a resistance gene. Secondly, an analysis called linkage disequilibrium, used to show evidence for positive selection, has been repeated with larger data sets and gives more ambiguous results.

Even though the population measurements for this mutation are less certain in humans, the evidence that CCR5 is critical for the timecourse of HIV infection is still very strong, and the mutation might still be an interesting marker for Northern European migrations (i.e. the Vikings).

An open-access discussion of CCR5-delta32 is here . I have blogged about this mutation and some interesting historical hypotheses here .

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