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Big differences in duplicated DNA distinguish chimp and human genomes

A study comparing the genomes of both humans and chimpanzees has found that much of the genetic difference between the two species came about in events called segmental duplications, in which segments of genetic code are copied many times in the genome. The study appears as a companion article to the draft sequence of the chimpanzee genome published in the Sept. 1 issue of the journal Nature.

Dr. Evan Eichler, associate professor of genome sciences at the University of Washington in Seattle, led this study, in addition to being involved in the Chimpanzee Genome Sequencing Project. Eichler, a Howard Hughes Medical Institute investigator, and his colleagues studied the chimp genome, looking for large-scale segmental duplications that consist of as many as 20,000 base pairs. They found that most of the change to the overall genome landscape between chimps and humans can be attributed to large segmental duplications. Such large-scale genetic events have altered more total base pairs - about 2.7 percent of the genome - than differences from single base-pair changes, which account for about 1.2 percent of the genome.

"For all the talk of the 1.2 percent single base-pair difference and the importance of those, there's even more difference between the species due to duplication events," said Eichler. "Now we need to learn the role of those duplication events in species evolution and disease."

The researchers divided the duplications into three groups: those found in the chimp but not the human, those found in the human but not the chimp, and those found in both species. Among the human-only duplications, some of those sections of the genome are implicated in human developmental disorders such as spinal muscular atrophy and Prader-Willi syndrome. Parts of those duplicated segments have only single copies in the chimp genome, and it is possible that the chimpanzee is therefore not predisposed to the same diseases as a human.

About two-thirds o f human-only duplications were new duplications in our species. They likely started out as a single copy of a segment in an ancestral species of both chimps and humans, and after the species split off from each other, that segment was duplicated many times in the human genome over millions of years. Most of the remaining one-third of duplication differences are due to deletion of segments in one of the two species - the segment is deleted from the genome, copy by copy, over time.

The researchers found that many of the species-specific duplications have also caused differences in gene expression. Of the individual genes within the duplicated segments of the genome, many of those that are specific to either chimps or humans are expressed differently in the two species. Gene expression is the process through which genetic information is changed into structures and functions in a living cell.

In addition to other differences, researchers found that among shared segmental duplications, humans often had fewer copies of those segments than chimps. The most dramatic example involved a piece of DNA near the site of an ancient chromosome fusion point on chromosome 2. In humans, this piece of DNA is represented as four copies, but in the chimp it has expanded to about 500 copies near the end of the chromosomes. Researchers don't yet understand why this particular piece of DNA has been independently unstable in the evolution of both the human and chimp genomes.


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Source:University of Washington


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