Skip to comments.EVOLUTION: Genome Comparisons Hold Clues to Human Evolution
Posted on 12/13/2003 12:46:20 PM PST by Lessismore
Despite decades of study, geneticists don't know what makes humans human. Language, long arms, and tree-climbing prowess aside, humans and our kissing cousins, chimpanzees, share practically all of our DNA. Genomic studies have suggested that the regulation of genes, rather than the genes themselves, set the two primate species apart.
But genes are still an important part of the story, says Michele Cargill, a geneticist at Celera Diagnostics in Alameda, California. She and her colleagues found key differences between chimp and human genome coding sequences, differences that propelled human evolution and sometimes lead to genetic diseases. Genes for olfaction and hearing, among others, have undergone distinct, rapid changes over the course of human evolution, whereas chimps' skeletal system genes have been similarly labile. The work, reported on page 1960, "is a valuable start to the genomic approach to identify 'humanness' and the genetic bases for human and ape disease differences," says Ajit Varki, a glycobiologist at the University of California, San Diego.
Cargill and her colleagues narrowed the number of genes to consider by culling all but those found in each of three species: chimp, human, and mouse. They gathered sequence data from Celera's complete human and mouse genomes and used the human data to identify chimp genes. (A public consortium has completed a draft chimp genome sequence; see below.) Of 7600 shared genes, the researchers identified those that had more than the expected number of base changes, given the normal mutation rates in each species. They concluded that 1547 human genes and 1534 chimp genes had experienced relatively rapid changes that likely endowed a survival advantage. The mouse data helped the team determine what genes to use and revealed the degree and direction of change in the primate genomes.
The study confirmed a report from earlier this year that a gene called the forkhead-box P2 transcription factor experienced unusually rapid evolutionary change in humans. The gene is necessary for proper speech development, and it's thought to have played an important role in human evolution. By analyzing the function and biochemical makeup of the proteins encoded by the genes they studied, Cargill and colleagues discovered other genes that might have had a similar effect.
In both chimps and humans, about 107 of the 1000 genes involved in cell signaling and 11 of 78 involved in amino acid metabolism have undergone major changes since the time of the species' last common ancestor 5 million years ago. But the genes didn't follow the same track in the two species, suggesting that they faced different pressures from natural selection. In humans, 27 of 48 olfactory proteins and three of 21 hearing proteins showed significant accelerated change, whereas that was not true in the chimp. In contrast, the chimp's genes for mesoderm development and skeletal structure proved unusually active.
At first, some of the patterns didn't seem to make sense, says co-author Andrew Clark, a population geneticist at Cornell University in Ithaca, New York. For example, one wouldn't expect rapid evolution of enzymes that modify proteins, because these enzymes are an essential part of basic metabolism and are not easily changed. But humans had 11 genes that ran contrary to this assumption. Upon reflection, the researchers realized that the alterations likely were adaptive when early humans began to consume more meat and needed the enzymes to digest the extra protein.
Rapid evolution of olfactory genes is more of a puzzle. Other research has shown that many of the human genes for proteins involved in recognizing odors are accumulating mutations. Mutations can have positive, negative, or no effect on the protein's utility. Because humans no longer rely strongly on their sense of smell to survive, any changes were assumed to have had no effect or a negative effect. Surprisingly, according to the new study, some olfaction genes have been evolving in a positive way: Their changes appear to have been selected for during human evolution. The genes may have promoted certain dietary changes or informed sexual selection, says Clark. Alternatively, olfactory receptors could be involved in more than just smell, says James Sikela, a genome scientist at the University of Colorado Health Sciences Center in Denver, who was not involved in the study.
The researchers were surprised to find out how many of the genes they studied are known to cause disease if damaged, including seven involved in amino acid metabolism. The discoveries bode well for geneticists: Looking for genes that have diverged since the time of humans' and chimps' common ancestor "could be another way to shorten the time to find these disease genes," says Cargill.
The mouse sequence served as a ready and useful reference, but Varki and others say that comparing human and chimp genes with the genome of a closer relative, such as another great ape, would reveal even more genes that defined the branches of the primate family tree.
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