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Primate Tip Sheet

Genome Research September 2005 Tip Sheet

Flipped, expelled, copied, and shrunk: Researchers document dramatic genome alterations during primate evolution.

The September 2005 issue of Genome Research presents a series of studies that provide insight into the evolution and variation of primate genomes. The issue will appear online and in print on September 1, concomitant with the publication of the chimpanzee genome sequence in the journal Nature.

Scrupulously shrinking genomes

Scientists generally believe that insertions of retroelements, or “jumping genes,” once established in a population, are irreversible and are maintained throughout evolution. This unidirectional theory of retroelement evolution, which calls for ever-expanding genome size, is challenged by work that appears in the September issue of Genome Research.

In this work, Dr. Dixie Mager and her colleagues performed a whole-genome comparison of the human, chimpanzee, and rhesus monkey sequences, and they identified 37 instances where a retroelement was present in rhesus (a more primitive primate species) but absent in either humans or chimpanzees. This indicated that these retroelements had been deleted during the evolution of the more recent primate species.

Intriguingly, the scientists further demonstrated that these deletions were mediated by short identical sequences that flank the retroelements. They extended the study to random, non-retroelement sequences and showed that deletions caused by short identical DNA sequences were a widespread genomic phenomenon. In fact, thousands of insertion-deletion sequence differences between the human and chimpanzee genomes were likely mediated by short identical sequences.

“Our work strongly suggests an important role for short, non-adjacent, identical segments of DNA in genomic deletions,” says Dr. Mager, “and it lends insight into deletion mechanisms that help to counterbalance genome expansion in primates.”

Dixie L. Mager, Ph.D. Senior Scientist, Terry Fox Laboratory, B.C. Cancer Research Centre,
Vancouver, Canada
Professor, Department of Medical Genetics, University of British Columbia
Phone: +1-604-675-8139
E-mail: dmager@bccrc.ca

Primate-specific genome plasticity at the Williams-Beuren syndrome locus.

The deletion of a 1.5-megabase segment spanning at least 26 genes on human chromosome 7 causes Williams-Beuren syndrome (WBS), a rare developmental disorder characterized by impaired cognition, dysmorphic facial features, and cardiovascular malformations. Repetitive elements flanking these 26 genes are thought to mediate the de novo deletion of this region in WBS, raising the possibility that it may be a particularly malleable and dynamic region of the genome.

In the September issue of Genome Research, Dr. Luis Pérez-Jurado and his colleagues report their investigation of the structure of the WBS region across numerous species. When they compared the WBS region in mouse (a non-primate mammal) and baboon (an early primate), they discovered that its structure was completely conserved in these two species, indicating that the WBS region has remained static in the rodent lineage since the divergence of rodents and primates approximately 80 million years ago.

In contrast, when comparing the WBS region among various primates (Japanese and rhesus macaque, olive and hamadryas baboon, orangutan, gorilla, chimpanzee, and human), they documented substantial variation, particularly species-specific duplications and intrachromosomal rearrangements. This indicated that during the past 12-16 million years of evolution, the region has undergone rapid and divergent evolution in primates. “The extraordinary rate of evolutionary turnover of this region suggests that it may be important in shaping primate speciation,” says Pérez-Jurado.

Luis A. Pérez-Jurado, M.D., Ph.D.
Associate Professor of Genetics
Universitat Pompeu Fabra, Barcelona, Spain
Phone: +34 93 542 2892
E-mail: luis.perez@upf.edu

Ditching drab DNA

Detrimental genetic mutations are usually expelled from a population by the forces of natural selection. If a deleterious mutation is adjacent to a polymorphism at a neutral locus, and there is no recombination – or exchange of genetic material – between the two, then the variation at the neutral locus is consequently lost in a process that scientists call “negative selection.” Until now, the role of negative selection in shaping patterns of human genetic variation has remained unknown.

“We can use the genomic sequence of the chimpanzee to help detect selection forces in humans,” explains Dr. Floyd Reed, lead author on a manuscript in the September issue of Genome Research. “The chimpanzee sequence reflects the similarities and differences of the human genome,” he says, “and we can use this to help quantify the expected contribution of negative selection to human genetic variation.”

Dr. Reed and his colleagues predicted large differences in levels of genetic variation across the human genome due to selection. “Negative selection could account for as much as a 62% reduction in variation in some regions of the genome,” explains Dr. Reed. “In the future, we can use these predictions to identify regions of the genome that have responded to Darwinian adaptation in humans, due to things like disease resistance or changes in cognitive function.”

Floyd A. Reed, Ph.D.
Department of Biology, University of Maryland
Phone: +1-301-405-6899
E-mail: freed@umd.edu

Digging for the roots of genomic variation

Non-coding sequences of the human and chimpanzee genomes differ by only 1.23%; however, this is just an average – some regions display much higher or lower levels of sequence divergence. Scientists have long believed that these patterns are not simply due to random differences in mutation rates, but rather are inherent structural features of the genomes. The factors underlying these large-scale patterns of genomic variation are the focus of a report by Ines Hellmann and colleagues in the September issue of Genome Research.

The researchers examined 19 different DNA sequence features that may shape patterns of human-chimp genomic variation, as well as patterns of human diversity. Most strikingly, they observed that recombination rates, GC and CpG content, simple repeat structures, and distance from centromere or telomere are significant predictors of human-chimp inter-species divergence and intra-species diversity in humans.

“Given that most of these features are likely to be proxies for higher-level properties, they explain a surprisingly high level of the variance in divergence,” says Hellmann. “It is curious to note that recombination rates belong to the best predictors, despite recent findings that they are evolving very quickly.”

Ines Hellmann
Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
Phone: +49-341-3550-509
E-mail: hellmann@eva.mpg.de

Please direct requests for complete manuscripts to Maria A. Smit, Ph.D., Assistant Editor, Genome Research (smit@cshl.edu) +1-516-422-4013).

Genome Research ( www.genome.org ) is an international, monthly, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics. The journal publishes novel genome-based studies and cutting-edge methodologies in comparative and functional genomics, bioinformatics, proteomics, evolutionary and population genetics, systems biology, epigenetics, and biotechnology.

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit www.cshlpress.com .

Genome Research issues press releases to highlight significant research studies that are published in the journal.

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