Tuesday, November 08, 2005

Secrets of the Dead: Descendants of plague survivors and HIV resistance

In September 1665, George Viccars, a tailor in the small, central-England village of Eyam, received a parcel of cloth ridden with plague-infected fleas from London. Four days later, Viccars died. By the end of the month, five more villagers had succumbed to the plague. The panicked town turned to their rector, William Mompesson, who persuaded them to quarantine the entire village to prevent the bacterium from spreading throughout the region. It seemed like suicide. A year later, the first outsiders ventured into Eyam, expecting a ghost town. Yet, miraculously, half the town had survived.
The normal form of the C-C chemokine receptor 5 (CCR5) is one of the cell surface molecules recognized by HIV-1, allowing the virus to infect cells in the immune system. A mutated form of the gene with a deletion of 32 base pairs ("delta32") can not be used by HIV, so people that have two copies of this mutated gene are virtually immune to HIV infection. People that have one copy of the delta32 variant are not complete immune, but have some protection against infection and the course of the disease is less severe when it occurs.

Like HIV, the plague bacterium infects white blood cells. NIH Scientist Dr. Stephen O'Brien hypothesized that the delta32 variant of CCR5 might also protect against plague infection. The village of Eyam appeared to be a good test case. The town has good church records of births, marriages and deaths dating from the 17th century, allowing O'Brien to figure out who had survived and who had perished in the plague. Analysis of the genes of the present-day descendants of plague survivors suggested that the hypothesis was correct.

14% of those tested in Eyam carried the delta32 allele. In comparison, essentially no native Africans or East Asians carry delta32. Further study showed that delta32 is carried by a similar portion of the population in other areas of Europe hit by plague and by the Caucasian population in America (largely settled by plague survivors and their descendants). The implication is that this is an example of natural selection at work on humans. When the plague hit Europe, killing millions, individuals carrying the delta32 variant of CCR5 were more likely to survive, have children, and, eventually, have descendants living today. The lack of delta32 in the native African population could explain in part why that continent has been so hard hit by the AIDS epidemic.

Links:
PBS web site: Secrets of the Dead

Ask a Geneticist: Is there a genetic reason some people survived the plague during the middle ages?
also: Ask a Geneticist: Could we introduce the delta32 gene into everyone's DNA? (non-technical)

• A recent article reanalyzing the genetic data suggesting that CCR5-delta32 in European populations is not a case of natural selection. (technical: Sabeti PC, Walsh E, Schaffner SF, Varilly P, Fry B, et al. (2005) The Case for Selection at CCR5-Δ32. PLoS Biol 3(11): e378)

(via Eastman's online genealogy newsletter)

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