SNIAHCRUOYGNIKNAYTSUJMI:

Genome Evolution | First, a Bang Then, a Shuffle: Did duplication fuel vertebrate genome evolution? (Ricki Lewis, Jan. 27, 2003, The Scientist)

Picture an imperfect hall of mirrors, with gene sequences reflecting wildly: That's the human genome. The duplications that riddle the genome range greatly in size, clustered in some areas yet absent in others, residing in gene jungles as well as within vast expanses of seemingly genetic gibberish. And in their organization lie clues to genome origins. "We've known for some time that duplications are the primary force for genes and genomes to evolve over time," says Evan Eichler, director of the bioinformatics core facility at the Center for Computational Genomics, Case Western Reserve University, Cleveland.

For three decades, based largely on extrapolations from known gene families in humans, researchers have hypothesized two complete genome doublings--technically, polyploidization--modified by gene loss, chromosome rearrangements, and additional limited duplications. But that view is changing as more complete evidence from genomics reveals a larger role for recent small-scale changes, superimposed on a probable earlier single doubling. Ken Wolfe, a professor of genetics at the University of Dublin, calls the new view of human genome evolution "the big bang" followed by "the slow shuffle." [...]

Polyploidy is rarer in animals, which must sort out unmatched sex chromosomes, than in plants, which reproduce asexually as well as sexually. "But polyploidization is maintained over evolutionary time in vertebrates quite readily, although rarely. Recent examples, from the last 50 million years ago or so, include salmonids, goldfish, Xenopus [frogs], and a South American mouse," says Postlethwait. On a chromosomal level, polyploidy may disrupt chromosome compatibility, but on a gene level, it is an efficient way to make copies. "Polyploidy solves the dosage problem. Every gene is duplicated at the same time, so if the genes need to be in the right stoichiometric relationship to interact, they are. With segmental duplications, gene dosages might not be in the same balance. This might be a penalty and one reason why segmental genes don't survive as long as polyploidy," Lynch says. [...]

Human genome sequence information has enabled Gu and others to test the 2R hypothesis more globally, reinstating one R. His group used molecular-clock analyses to date the origins of 1,739 duplications from 749 gene families.8 If these duplications sprang from two rounds of polyploidization, the dates should fall into two clusters. This isn't exactly what happened. Instead, the dates point to a whole genome doubling about 550 million years ago and a more recent round of tandem and segmental duplications since 80 million years ago, when mammals radiated.

Ironically, sequencing of the human genome may have underestimated the number of duplications. The genome sequencing required that several copies be cut, the fragments overlapped, and the order of bases derived. The algorithm could not distinguish whether a particular sequence counted twice was a real duplication, present at two sites in the genome, or independent single genes obtained from two of the cut genomes.

Eichler and his group developed a way around this methodological limitation. They compare sequences at least 15,000 bases long against a random sample of shotgunned whole genome pieces. Those fragments that are overrepresented are inferred to be duplicated. The technique identified 169 regions flanked by large duplications in the human genome.

Although parts of the human genome retain a legacy of a long-ago total doubling, the more recent, smaller duplications provide a continual source of raw material for evolution. "My view is that both happen. A genome can undergo polyploidy, duplicating all genes at once, but the rate of segmental duplications turns out to be so high that every gene will have had the opportunity to duplicate" by this method also, concludes Lynch. It will be interesting to see how the ongoing analyses of the human and other genome sequences further illuminate the origins and roles of duplications.

It would appear they've identified several of the precise moments at which God intervened to create Man, in these cases doubling the entire genome to force evolution onto chosen tracks. Posted by Orrin Judd at January 31, 2003 8:48 PM