The findings, published in this week's early online edition of the Proceedings of the National Academy of Sciences, are among the first evidence of a novel link between cell surface sugars, Darwinian sexual selection, and immune function in the context of human origins
Sialic acids are sugar molecules found on the surfaces of all animal cells, where they serve as vital contact points for interaction with other cells and with the surrounding environment, including as targets for invasive pathogens. For millions of years, the common ancestors of humans and other apes shared a particular kind of sialic acid known as N-glycolylneuraminic acid or Neu5Gc. Then, for reasons possibly linked to a malarial parasite (http://health.ucsd.edu/news/2005/Pages/09_08_Varki.aspx) that bound Neu5Gc, a gene mutation three million or so years ago inactivated the human enzyme involved in making the molecule. Instead, humans began producing more of a slightly different form of sialic acid called Neu5Ac, the precursor of Neu5Gc.
"This occurred at about the same time as early humans were apparently becoming major predators in their environment," said Pascal Gagneux, PhD, an evolutionary biologist and associate professor of cellular and molecular medicine at UC San Diego. "It's hard to be sure exactly what happened because evolution works on so many things simultaneously, but the change in sialic acid meant that early humans developed an immune response to Neu5Gc. It became viewed by their immune systems as foreign, something to be destroyed. At about the same time, they started eating red meat, a major source of Neu5Gc, which may have further stimulated the immune response."
"Over time, this incompatibility would reduce and then eliminate individuals with Neu5Gc," said Gagneux. "Oddly enough, based on our theoretical model, the process works faster when the fertility rate is only slightly decreased, rather than producing 100 percent infertility."
Gagneux noted that the findings add further weight to the concept of "speciation by infection," in which a combination of infectious diseases suffered by a particular population could predispose that population to diverge from other populations due to reproductive incompatibility. In the case of early humans, one driver may have been female immunity to Neu5Gc.
Previous studies (http://ucsdnews.ucsd.edu/newsrel/health/Varki%208%2022.htm) have shown that the loss of Neu5Gc occurred about two to three million years ago, which happens to be about the time of emergence of Homo ergaster/erectus, the likely ancestor of humans.
"We suggest that the immune mechanism described here was involved in the origin of the genus Homo," said study co-author Ajit Varki, MD, professor of medicine and cellular and molecular medicine and director of the Center for Academic Research and Training in Anthropogeny at UC San Diego.
Co-authors of the paper are Darius Ghaderi, Fang Ma, Miriam Cohen, Patrick Secrest and Rachel E. Taylor, all of the Center for Academic Research and Training in Anthropogeny, Glycobiology Research and Training Center and departments of Medicine and Cellular and Molecular Medicine, UC San Diego; and Stevan Springer, Department of Biology, University of Washington, Seattle.
Scott LaFee | EurekAlert!
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