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Genetic Divergence Of Man From Chimp Has Aided Human Fertility But Could Have Made Us More Prone To Cancer

May 15, 2005
Cornell University
The one percent of the human and chimpanzee genomes that differ from each other reveal how evolution has individually shaped the two species' genes since sharing a common ancestor five million years ago, according to a study led by Cornell University researchers Rasmus Nielsen, Andrew Clark and Carlos Bustamante.

Distribution of Mutations: The figure shows the number of synonymous and nonsynonymous nucleotide differences in 13,731 human--chimpanzee orthologous gene pairs. From: Nielsen R, Bustamante C, Clark AG, Glanowski S, Sackton TB, et al. (2005) A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees. PLoS Biol 3(6): e170

ITHACA, N.Y. -- Chimpanzees and humans share a common ancestor, and even today 99 percent of the two species' DNA is identical. But since the paths of man and chimp diverged 5 million years ago, that one percent of genetic difference appears to have changed humans in an unexpected way: It could have made people more prone to cancer.

A comparative genetic study led by Cornell University researchers suggest that some mutations in human sperm cells might allow them to avoid early death and reproduce, creating an advantage that ensures more sperm cells carry this trait. But this same positive selection could also have made it easier for human cancer cells to survive.

"If we are right about this, it may help explain the high prevalence of cancer," says Rasmus Nielsen, lead author of the paper, and a former assistant professor of the Department of Biological Statistics and Computational Biology at Cornell who is now a professor at the University of Copenhagen, Denmark. The study, published in a recent issue of PLoS Biology (Vol. 3, Issue 6), a peer-reviewed, open-access journal published by the Public Library of Science (PLoS), focuses on identifying biological processes where positive selection -- adaptations that lead to new directions -- produced evolutionary changes that can be identified in the genomes of both humans and chimps.

To make these comparisons, the researchers used chimpanzee DNA sequence data generated by Celera Genomics of Rockville, Md. The chimpanzee and human versions of each gene were aligned, and on average they differ at only slightly more than 1 percent of the positions in the DNA.

The researchers' searched out the relatively few genes (13,731 sequences) that have diverged the most since sharing a common ancestor, most likely a primate that looked like a cross between a gorilla, chimp and human. While the scientists more or less expected to see that immune defense systems in each species have rapidly evolved separately to keep pace with attacking, mercurial bacteria and viruses, they were surprised to find that genes associated with the brain were practically the same.

One of the more interesting observations occurred in some genes that govern cell death in sperm cells and tumor cells alike. Both types of cells use a mechanism called apoptosis -- a pathway that includes genes that program a cell's demise and death. During the production of sperm cells, for example, apoptosis kills many of the cells before they reach maturity. But mutations in these genes could inhibit apoptosis in some sperm cells, allowing more sperm to reach maturity, reproduce again and ensure that future cells will carry the gene that defuses early self-destruction.

Unfortunately, this same machinery also allows cancer cells to live on. The researchers suspect that some mutations that allow sperm cells to increase their chances of reproduction might also diminish an organism's ability to turn off tumor cell growth and fight cancer.

"Eliminating cancer cells by apoptosis is one of the main processes used by the organism to fight cancer," says Nielsen.

According to the study, immune defense genes also have evolved quickly, creating greater genetic differences between humans and chimps.

"The main reason why immune- and defense-related genes have diverged is probably because they are involved in an evolutionary arms race with pathogens," says Nielsen. "Viruses and other pathogens evolve very quickly, and the human immune system is constantly being challenged by the emergence of new pathogenic threats." Pathogens such as the bubonic plague, AIDS and influenza put constant pressures on the human immune system to adapt by positive selection.

Surprisingly, the study found that genes associated with the brain could not explain apparent differences in brain form, function and power between humans and chimps. The researchers wonder if a few small genetic changes had big effects on how the brains of each species have developed.

"It could be relatively few switch genes that account for the difference," says Andrew Clark, a co-author on the study and a professor of molecular biology and genetics at Cornell. Carlos Bustamante, an assistant professor of Biological Statistics and Computational Biology at Cornell, was also a major contributor to this study.

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Materials provided by Cornell University. Note: Content may be edited for style and length.

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