Flipped, Expelled, Copied, And Shrunk: Researchers Document Dramatic Genome Alterations During Primate Evolution

Scrupulously shrinking genomes

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

In this work, Dr. Dixie Mager and her colleagues performed awhole-genome comparison of the human, chimpanzee, and Rhesus monkeysequences, and they identified 37 instances where a retroelement waspresent in Rhesus (a more primitive primate species) but absent ineither humans or chimpanzees. This indicated that these retroelementshad been deleted during the evolution of the more recent primatespecies.

Intriguingly, the scientists further demonstrated that thesedeletions were mediated by short identical sequences that flank theretroelements. They extended the study to random, non-retroelementsequences and showed that deletions caused by short identical DNAsequences were a widespread genomic phenomenon. In fact, thousands ofinsertion-deletion sequence differences between the human andchimpanzee 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 tocounterbalance genome expansion in primates."

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

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

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

In contrast, when comparing the WBS region among variousprimates (Japanese and Rhesus macaque, olive and hamadryas baboon,orangutan, gorilla, chimpanzee, and human), they documented substantialvariation, particularly species-specific duplications andintrachromosomal rearrangements. This indicated that during the past12-16 million years of evolution, the region has undergone rapid anddivergent evolution in primates. "The extraordinary rate ofevolutionary turnover of this region suggests that it may be importantin shaping primate speciation," saysPérez-Jurado.

Ditching drab DNA

Detrimental genetic mutations are usually expelled from apopulation by the forces of natural selection. If a deleteriousmutation is adjacent to a polymorphism at a neutral locus, and there isno recombination -- or exchange of genetic material -- between the two,then the variation at the neutral locus is consequently lost in aprocess that scientists call "negative selection." Until now, the roleof negative selection in shaping patterns of human genetic variationhas remained unknown.

"We can use the genomic sequence of the chimpanzee to helpdetect selection forces in humans," explains Dr. Floyd Reed, leadauthor on a manuscript in the September issue of Genome Research."The chimpanzee sequence reflects the similarities and differences ofthe human genome," he says, "and we can use this to help quantify theexpected contribution of negative selection to human geneticvariation."

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

Digging for the roots of genomic variation

Non-coding sequences of the human and chimpanzee genomes differby only 1.23%; however, this is just an average -- some regions displaymuch higher or lower levels of sequence divergence. Scientists havelong believed that these patterns are not simply due to randomdifferences in mutation rates, but rather are inherent structuralfeatures of the genomes. The factors underlying these large-scalepatterns of genomic variation are the focus of a report by InesHellmann and colleagues in the September issue of Genome Research.

The researchers examined 19 different DNA sequence features thatmay shape patterns of human-chimp genomic variation, as well aspatterns of human diversity. Most strikingly, they observed thatrecombination rates, GC and CpG content, simple repeat structures, anddistance from centromere or telomere are significant predictors ofhuman-chimp inter-species divergence and intra-species diversity inhumans.

"Given that most of these features are likely to be proxies forhigher-level properties, they explain a surprisingly high level of thevariance in divergence," says Hellmann. "It is curious to note thatrecombination rates belong to the best predictors, despite recentfindings that they are evolving very quickly."