|Title||Neutral Substitutions Occur at a Faster Rate in Exons Than in Noncoding DNA in Primate Genomes|
|Publication Type||Journal Article|
|Year of Publication||2003|
|Authors||Subramanian, S, Kumar, S|
|Keywords||2010-10-22, fitness effects, genomics, molecular clock, mutation, mutation rate|
Point mutation rates in exons (synonymous sites) and noncoding (introns and intergenic) regions are generally assumed to be the same. However, comparative sequence analyses of synonymous substitutions in exons (81 genes) and that of long intergenic fragments (141.3 kbp) of human and chimpanzee genomes reveal a 30%–60% higher mutation rate in exons than in noncoding DNA. We propose a differential CpG content hypothesis to explain this fundamental, and seemingly unintuitive, pattern. We find that the increased exonic rate is the result of the relative overabundance of synonymous sites involved in CpG dinucleotides, as the evolutionary divergence in non-CpG sites is similar in noncoding DNA and synonymous sites of exons. Expectations and predictions of our hypothesis are confirmed in comparisons involving more distantly related species, including human–orangutan, human–baboon, and human–macaque. Our results suggest an underlying mechanism for higher mutation rate in GC-rich genomic regions, predict nonlinear accumulation of mutations in pseudogenes over time, and provide a possible explanation for the observed higher diversity of single nucleotide polymorphisms (SNPs) in the synonymous sites of exons compared to the noncoding regions.
Neutral Substitutions Occur at a Faster Rate in Exons Than in Noncoding DNA in Primate Genomes
For years, I've worked on their bones. Now I'm working on their genes. Read more about the science studying these ancient people.
From a finger bone of an ancient human came the record of a completely unexpected population. My lab is working on the science of the Denisova genome.
The advent of agriculture caused natural selection to speed up greatly in humans. We're uncovering some of the ways that populations have rapidly changed during the last 10,000 years.