Washington, Dec 14: Researchers at the University of California has found that the loss of genes has contributed to the evolution of the human species. he study led by Biomolecular engineering professor David Haussler carried out the first systematic computational analysis to identify long-established genes that have been lost across millions of years of evolution that might contribute to adaptation.
Researchers at the University of California has found that the loss of genes has contributed to the evolution of the human species. he study led by Biomolecular engineering professor David Haussler carried out the first systematic computational analysis to identify long-established genes that have been lost across millions of years of evolution that might contribute to adaptation.
"This is the first study designed to search the entire genome for recent loss of genes that do not have any near-duplicate copies elsewhere in the genome," said Haussler
"These are likely to be the more important gene losses," he added.
The co-authors of the study are postdoc Jingchun Zhu, graduate students Zack Sanborn and Craig Lowe, technical projects manager Mark Diekhans, and evolutionary biologist Tom Pringle.
Jingchun Zhu, first author of the study employed a software program called TransMap developed Diekhans.
It compared the mouse and human genomes, searching for genes having changes significant enough to render them non-functional somewhere during the 75 million years since the divergence of the mouse and the human.
"The idea that gene losses might contribute to adaptation has been kicked around, but not well studied," said Zhu.
The study focused on losses caused by mutations that disrupt the open reading frame (ORF-disrupting mutations) which can be due to insertion or substitution of a DNA base alter the instructions delivered by the DNA, or changes that occur when a large portion of a gene is deleted altogether or moves to a new place on the genome.
The researchers studied the dog genome as it had diverged from ancient common ancestors long ago.
"We used the dog genome as an out-group to filter out false positives," because the dog diverged from our ancient common ancestor earlier than the mouse," Sanborn explained.
"If a gene is still living in both dog and mouse but not in human, it was probably living in the common ancestor and then lost in the human lineage," he added.
They identified 26 losses of long-established genes, including 16 that were not previously known and compared it with genomes of the human, chimpanzee, rhesus monkey, mouse, rat, dog, and opossum to estimate the amount of time the gene was functional before it was lost.
The researchers discovered a gene for acyltransferase-3 (ACYL3).
"This is an ancient protein that exists throughout the whole tree of life," said Zhu.
The analyses disclosed that this gene contained a nonsense mutation in human and chimp, and it appeared to be still functional in rhesus.
"Acyltransferase-3 was not the only lost gene that doesn't have any close functional homologues in the human genome. A highlight of our research was that we were able to find a list of these 'orphan losses,'" Zhu added.
"Some of them have been functional for more than 300 million years, and they were the last copies left in the human genome," he added.
"These orphan genes may be interesting candidates for experimental biologists to explore.
"It would be interesting to find out what was the biological effect of these losses. Once their function is well characterized in species that still have active copies, we could maybe speculate about their effects on human evolution," Zhu concluded.
The findings are published in the December 14 issue of PLoS Computational Biology. (ANI)
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