Microsatellite variation and recombination rate in the human genome

Background (purifying) selection on deleterious mutations is expected to re move linked neutral mutations from a population, resulting in a positive co rrelation between recombination rate and levels of neutral genetic variatio n, even for markers with high mutation rates. We tested this prediction of the background selection model by comparing recombination rate and levels o f microsatellite polymorphism in humans. Published data for 28 unrelated Eu ropeans were used to estimate microsatellite polymorphism (number of allele s, heterozygosity, and variance in allele size) for loci throughout the gen ome. Recombination rates were estimated from comparisons of genetic and phy sical maps. First, we analyzed 61 loci from chromosome 22, using the comple te sequence of this chromosome to provide exact physical locations. These 6 1 microsatellites showed no correlation between levels of variation and rec ombination rate. We then used radiation-hybrid and cytogenetic maps to calc ulate recombination rates throughout the: genome. Recombination rates varie d by more than one order of magnitude, and most chromosomes showed signific ant suppression of recombination near the centromere. Genome wide analyses provided no evidence for a strong positive correlation between recombinatio n rate and polymorphism, although analyses of loci with at least 20 repeats suggested a weak positive correlation. Comparisons of microsatellites in l owest-recombination and highest-recombination regions also revealed no diff erence in levels of polymorphism. Together, these results indicate that bac kground selection is not a major determinant of microsatellite variation in humans.