New data suggest that the accumulation of genetic changes is not solely determined by natural selection. A study by University of Chicago researchers contradicts conventional theory by showing that the percentage of mutations accepted in evolution is also strongly swayed by the speed at which new mutations arrive at a gene: the faster the speed of new mutations, the greater the percentage of those mutations accepted.
"We've discovered a striking phenomenon that challenges a paradigm of molecular evolution that has been around for several decades," said lead author Bruce Lahn, PhD, assistant professor of genetics at the University of Chicago and Howard Hughes Medical Institute investigator. "As such, it may cause a significant shift in the field."
The researchers report their findings in the July 2005, issue of the journal Trends in Genetics. Other authors are Gerald Wyckoff, PhD, previously a postdoctoral fellow in Lahn's lab and now an assistant professor at the University of Missouri-Kansas City, and Christine Malcom and Eric Vallender, both graduate students in Lahn's lab.
For more than three decades, molecular evolutionists have thought that no matter how many genetic mutations show up on a specific gene, whether or not those mutations become fixed in the species is determined primarily by natural selection. The new study shows that the speed at which these new mutations arrive also affects whether the mutations become fixed.
Lahn's team looked at nearly 6,000 genes in their study. For each gene, they compared sequences between two mammalian species. This enabled them to measure the mutation rate of the gene – specifically, the rate of those mutations that do not affect the protein's structure, called synonymous mutation (Ks). These mutations are functionally neutral, which means natural selection is not a factor in whether they are accepted during evolution.
Lahn's team also looked at the mutation rate of nonsynonymous changes (Ka)--the rate of those mutations that do affect protein structure. These mutations are typically subject to natural selection. A nonsynonymous mutation will get accepted into or bounced out of the population based upon how the change alters protein function.
The researchers then studied the Ka/Ks ratio. A low Ka/Ks ratio indicates strong selection; conversely, a high ratio, weak selection. Some genes have a ratio of 0, which means protein changes are not accepted. It is, in a sense, "perfect."
For a pseudogene--a stretch of DNA sequence that resembles a gene but has no function--its Ka/Ks ratio is approximately 1.0, which means that synonymous and nonsynonymous mutations are accepted at the same rate since the gene is functionally irrelevant.
For a gene that is highly functional and important for the organism, its Ka/Ks ratio is typically low. For example, if a gene has a Ka/Ks ratio of 0.1, it means that it's highly selective and is only accepting 10 percent of the nonsynonymous mutations.