AIDS in Africa has potential to affect human evolution, UC Berkeley scientists report

May 29, 2001

Berkeley - If anyone doubts that epidemics can affect the course of human evolution, take a look at AIDS.

Three biologists from the University of California, Berkeley, show in this week's issue of Nature (May 31, 2001) that over a period of several generations, AIDS could alter the frequency of specific genetic mutations in African populations, delaying the average time between HIV infection and onset of disease.

Though this genetic evolution probably won't impact health management in Africa - public health experts pray that drugs or vaccines will soon cut the high mortality and infection rates on the continent - it provides a rare example of how epidemic infectious diseases can exert selective pressure on the human genome.

The only other widely accepted example of selection of this intensity caused by an infectious disease acting on a gene conferring resistance is malaria. Over hundreds of years, the disease selected for certain genes that increased the chance of human survival to reproductive age, but which caused other blood diseases, primarily sickle cell anemia but also the thalassemias.

"Natural selection in the case of AIDS in Africa is as strong as the selection malaria had on the gene that causes sickle cell anemia," said mathematical biologist Montgomery Slatkin, professor of integrative biology at UC Berkeley. "That's what surprised us."

Charles Darwin coined the term "natural selection" and focused on it as the driving force of evolution, whereby slight variations that increase the number of offspring tend to become more common in successive generations. The same idea is embodied in the phrase "survival of the fittest."

Scientists have speculated that infectious diseases that reached epidemic proportions over the course of history - from bubonic plague and measles to smallpox - have affected human evolution, selecting for genes that reduce mortality before or through the reproductive years. Evidence, however, is hard to find, Slatkin said.

That was why he and postdoctoral fellows Paul Schliekelman and Chad Garner took notice when a United Nations study of AIDS in Africa reported that the prevalence of the disease approached 40 percent in some countries. Given today's infection rate and mortality, the lifetime chance of a 15-year-old boy dying of AIDS is 65 percent in South Africa and nearly 90 percent in Botswana.

Diseases serious enough to affect this proportion of the population can, by natural selection, affect genetic variation in the population.

The UC Berkeley group focused on a gene called CCR5 that affects the latency period for AIDS, that is, how long after infection symptoms appear. Four years ago, other scientists showed that some people in Africa have a mutation in the CCR5 gene that makes them develop AIDS two to four years earlier than average, while others have a different mutation that delays symptoms by two to four years.

Using data on birth and death rates in South Africa in the 1980s, before the AIDS epidemic began, and employing standard epidemiologic and population genetics models, they showed that over the course of 100 years, the gene conferring greater resistance to AIDS would increase in frequency from 40 percent of the population to more than half. The mutation that makes people more susceptible would decrease from 20 percent of the population to only 10 percent. The shift in frequency of these genes would effectively lengthen the average latency by one year, from 7.8 years to 8.8 years.

The frequency shift is primarily due to the opportunity for continued reproduction during the extra two to four years, allowing those with the resistant version of the gene, or allele, to produce 10-20 percent more children than those with the susceptible allele. That amounts to about one extra child per person, Slatkin said.

"The change in gene frequencies will happen over a long time period, not immediately," Schliekelman said. "But if the disease remains unchecked, it will gradually select for the gene that delays the onset of the disease."

Interestingly, a different mutation, called delta-32, in the CCR5 gene is found in northern Europeans, though rarely in Africans. A person with two copies of this mutated CCR5 gene apparently is completely resistant to HIV infection. CCR5, which codes for a receptor on the surface of immune cells, seems to be important in AIDS because the HIV virus locks onto it before entering cells. Mutations that alter or delete the receptor would thus make it more difficult or impossible for HIV to infect immune cells.

Slatkin said that it appears the CCR5 mutation in northern Europe has been selected for in the past 700 years, possibly by another epidemic disease with as strong a selective pressure as malaria and AIDS. Some scientists have suggested that bubonic plague, which decimated Europe during the 14th century, may have been the cause.

Slatkin, however, suspects it was measles or some disease that strikes young children, since that would have a greater effect on reproduction than diseases like plague, which affects all ages. Bubonic plague, though devastating, also did not last long enough to exert sufficient selection on resistance genes, he said.
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NOTE: Slatkin, Schliekelman and Garner can be reached at 510-643-6300 or 643-6299, or via e-mail at slatkin@socrates.berkeley.edu, pdschlie@socrates.berkeley.edu and cgarner@socrates.berkeley.edu, respectively.

University of California - Berkeley

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