Thursday, December 21, 2006

 

Humans and Chimps: Close But Not That Close..

Approximately 6 percent of human and chimp genes are unique to those species, report scientists from Indiana University Bloomington and three other institutions. The new estimate, reported in the inaugural issue of Public Library of Science ONE (December 2006), takes into account something other measures of genetic difference do not - the genes that aren't there.

That isn't to say the commonly reported 1.5 percent nucleotide-by-nucleotide difference between humans and chimps is wrong, said IUB computational biologist Matthew Hahn*, who led the research. IUB postdoctoral researcher Jeffery Demuth** is the paper's lead author.

"Both estimates are correct in their own way," Hahn said. "It depends on what you're asking. There isn't a single, standard estimate of variation that incorporates all the ways humans, chimps and other animals can be genetically different from each other."

By studying "gene families" - sets of genes in every organism's genome that are similar (or identical) because they share a common origin - the scientists also provide new information about the evolution of humanness. After surveying gene families common to both humans and chimps, the researchers observed in the human genome a significant increase in the duplication of genes that influence brain functions.

"Our results support mounting evidence that the simple duplication and loss of genes has played a bigger role in our evolution than changes within single genes," Hahn said.

That finding complements reports by University of Colorado and University of Michigan researchers in the journals Science and PLoS Biology earlier this year, in which researchers showed that both gains and losses of individual genes have contributed to human divergence from chimpanzees and other primates.

Hahn and his research partners examined 110,000 genes in 9,990 gene families that are shared by humans, common chimpanzees (Pan troglodytes), mice, rats and dogs. The scientists found that 5,622, or 56 percent, of the gene families they studied from these five species have grown or shrunk in the number of genes per gene family, suggesting changes in gene number have been so common as to constitute an evolutionary "revolving door."

The researchers paid special attention to gene number changes between humans and chimps. Using a statistical method they devised, the scientists inferred humans have gained 689 genes (through the duplication of existing genes) and lost 86 genes since diverging from their most recent common ancestor with chimps. Including the 729 genes chimps appear to have lost since their divergence, the total gene differences between humans and chimps was estimated to be about 6 percent.

Hahn said any serious measure of genetic difference between humans and chimps must incorporate both variation at the nucleotide level among coding genes and large-scale differences in the structure of human and chimp genomes. The real question biologists will face is not which measure is correct but rather which sets of differences have been more important in human evolution.

"That's not for me to decide," he said.

Source: Indiana University "Human-chimp difference may be bigger" Tuesday, December 20 2006

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Based on the PLoS ONE open access paper:

"The Evolution of Mammalian Gene Families"

Citation: Demuth JP, Bie TD, Stajich JE, Cristianini N, Hahn MW (2006) The Evolution of Mammalian Gene Families. PLoS ONE 1(1): e85. doi:10.1371/journal.pone.0000085

Abstract

Gene families are groups of homologous genes that are likely to have highly similar functions. Differences in family size due to lineage-specific gene duplication and gene loss may provide clues to the evolutionary forces that have shaped mammalian genomes. Here we analyze the gene families contained within the whole genomes of human, chimpanzee, mouse, rat, and dog. In total we find that more than half of the 9,990 families present in the mammalian common ancestor have either expanded or contracted along at least one lineage. Additionally, we find that a large number of families are completely lost from one or more mammalian genomes, and a similar number of gene families have arisen subsequent to the mammalian common ancestor. Along the lineage leading to modern humans we infer the gain of 689 genes and the loss of 86 genes since the split from chimpanzees, including changes likely driven by adaptive natural selection. Our results imply that humans and chimpanzees differ by at least 6% (1,418 of 22,000 genes) in their complement of genes, which stands in stark contrast to the oft-cited 1.5% difference between orthologous nucleotide sequences. This genomic "revolving door" of gene gain and loss represents a large number of genetic differences separating humans from our closest relatives.

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*From Mathew Hahn's homepage:

...Divergence in genetic networks: Proteins do not evolve in isolation, but rather as components of complex genetic networks. Therefore, a protein's position in a network may indicate how central it is to cellular function, and hence how constrained it is evolutionarily. We have examined the protein-protein interaction networks in yeast, worm, and fly, and have found that proteins with a more central position in all three networks - regardless of the number of direct interactors - evolve more slowly and are more likely to be essential for survival. By studying various types of genetic networks in a number of different genomes, we can begin to understand the determinants of sequence evolution - and therefore of phenotypic evolution.

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**From Jeffery Demuth's homepage:

...There is a growing appreciation that many major morphological and functional changes in evolution result from duplications that range in size from genes to whole genomes. Furthermore, differential silencing of duplicate gene copies between populations may contribute to speciation. Unlike the analysis of orthologous sequences, where there are widely accepted neutral expectations for molecular evolution, there is no corresponding framework for the study of gene duplication and loss. While many studies attribute large changes in the size of gene families to natural selection, there is no solid theoretical foundation for what might be expected purely due to stochastic gain and loss of genes. To address this deficiency, we have developed a likelihood-based method that makes efficient use of genomic data in a phylogenetic context. The method allows us to identify gene families that are expanding or contracting significantly faster than can be explained by a random process.

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