Loss of Control

A large number of harmful mutations have accumulated in the genomes of humans and chimpanzees, according to a new study. The mutations may be the result of the historically small breeding populations and may explain why humans and chimps have different levels of expression of some genes.

Just having genes isn't enough--they've got to be turned on. Regions of DNA that surround genes frequently regulate when and where genes get activated. These regions tend to be conserved over evolution, and scientists have thus assumed that too many mutations in these regions are fatal.

But a new study by Peter Keightley of the University of Edinburgh and colleagues suggests this may not be the case. The researchers looked at mutation rates in likely regulatory sequences of rat and mouse genomes. They found that these regulatory sequences had acquired fewer mutations than had sequences thought to mutate at the genome's baseline rate. In humans and chimpanzees, however, the researchers discovered that DNA sequences in regulatory areas have accumulated nearly as many mutations as have sequences evolving at the baseline level. Using a statistical test, the authors show that these mutations are not adaptive and are most likely harmful. The researchers report their findings in next month's issue of Public Library of Science Biology.

The team speculates that detrimental mutations have survived in humans and chimps because these species have had much smaller breeding populations than rodents throughout evolution. The effects of these deleterious mutations in humans and chimpanzees are probably either inconsequential or else they are compensated by adaptive changes elsewhere in the genome, Keightley says. The mutations may also explain why some genes have much different expression levels than would be expected between humans and chimps.

Martin Kreitman, an evolutionary geneticist at the University of Chicago, is concerned about the accuracy of matching up the mouse and rat genomes, but says the basic message of the study is "certainly correct." He adds, "It's inevitable that there has been some accumulation of deleterious mutations that would have been purged had [humans and chimpanzees] had larger population sizes."

Related sites
Deleterious mutations and population size
Genetic drift
The PLoS Biology paper
Peter D. Keightley CV and research interests