Today at 3:00 pm: Dr. Yi's seminar, 5th floor 38AFrom: Alexey Kondrashov [kondrashov@ncbi.nlm.nih.gov]
Sent: Thursday, May 08, 2003 2:08 PM
To: ncbi-seminar@ncbi.nlm.nih.gov
Subject: Today at 3:00 pm: Dr. Yi's seminar, 5th floor 38A

Mutation Rate Variation in the Genomes of Higher Primates

Soojin Yi, University of Chicago

We investigated several aspects of mutation rate variation in the genomes of higher primates. First, we reexamined the classical molecular clock hypothesis such as the proposal of a global clock for all eutherians, i.e., a single global rate of 2.2 ¥ 10-9 substitutions per nucleotide site per year (Kumar & Subramanian 2002). We used non-coding, non-repetitive DNA data from Old World monkeys (OWMs), chimpanzees, and humans, and used fossil records to calibrate the molecular clock. From this we show that mutation rates in noncoding, non-repetitive DNA of higher primates are half of the proposed global rate and much smaller than the commonly used rate (3.5 ¥ 10-9) for eutherians. In addition, with the New World monkey lineage as an outgroup, we estimate that the rate of substitution in introns is 30% higher in the OWM lineage than in the human lineage. Second, we ask whether there exists regional variation in the mutation rates in the genomes of higher primates. Using new and existing intron sequence data from higher primates, we find significant rate variation among genomic regions and a positive correlation between the rate of substitution and the GC content. We further explore the effect of recombination on evolutionary rates by comparing patterns of molecular evolution of the pseudoautosomal region (PAR) and the X-specific region. In mouse, a dramatically increased level of nucleotide substitution in PAR region has been reported, which is taken as an evidence of the mutagenetic effect of recombination (Perry and Ashworth 1999; Montoya-Burgos et al. 2003). In contrast, we show that the pattern of molecular evolution of the XG locus at the pseudoautosomal boundary (PAB) in humans is not affected by recombination. On the other hand, we found that the GC contents of the sequences are strongly correlated with the degree of divergence in this region. In other words, we show that the effects of GC content and recombination on evolutionary rates are decoupled in the human PAB.