PMC:1271393 / 40564-43577 JSONTXT

{"project":"2_test","denotations":[{"id":"16252244-11237013-2049638","span":{"begin":512,"end":516},"obj":"11237013"},{"id":"16252244-11452081-2049639","span":{"begin":672,"end":676},"obj":"11452081"},{"id":"16252244-11237013-2049640","span":{"begin":1131,"end":1135},"obj":"11237013"},{"id":"16252244-11237013-2049641","span":{"begin":1584,"end":1588},"obj":"11237013"},{"id":"16252244-12213772-2049642","span":{"begin":1603,"end":1607},"obj":"12213772"},{"id":"16252244-12466850-2049643","span":{"begin":1626,"end":1630},"obj":"12466850"},{"id":"16252244-12740762-2049644","span":{"begin":1648,"end":1652},"obj":"12740762"}],"text":"Contrasting Patterns of Diversity in the CD209/CD209L Region\nOur diversity study revealed completely different patterns for the two genes. First, levels of nucleotide diversity (π) were found to be much lower for CD209 than for CD209L (table 2). On the basis of 1.42 million SNPs, the International SNP Map Working Group defined 7.5×10−4 as the average value of nucleotide diversity for the human genome and showed that 95% of all bins presented π values varying from 2.0×10−4 to 15.8×10−4 (Sachidanandam et al. 2001). In addition, an independent study analyzed nucleotide and haplotype diversity for 313 genes and defined the average π value as 5.4×10−4 (Stephens et al. 2001). In this context, the values observed for CD209 (3–7×10−4) are in agreement with these genome estimations, with the exception of the African sample, which showed extreme levels of diversity (26.0×10−4) because of the presence of cluster A. By contrast, the π values observed for CD209L (16–18×10−4) are at least twofold higher than average genome estimates and fall into the upper limit of the 95% CI defined by the SNP Consortium (Sachidanandam et al. 2001). This contrast in nucleotide diversity between the two genes can be explained either by a disparity in local mutation rates or by actual differences in selective pressures. However, no major differences in mutation rates (1.57×10−9 vs. 1.70×10−9) were observed between the two homologues, nor was there substantial variation in GC content, which has been positively correlated with mutation rates and levels of polymorphisms (Sachidanandam et al. 2001; Smith et al. 2002; Waterston et al. 2002; Hellmann et al. 2003). Indeed, the GC content for CD209 (53.7%) was slightly higher than that observed for CD209L (50.9%), which reinforces the idea that different selective pressures may indeed have been the driving force behind the distinct patterns of diversity observed. Second, the patterns of repeat variation in the neck region also turned out to be strikingly different between the two genes. CD209 showed levels of heterozygosity of only 2%, whereas CD209L presented an extraordinarily high level of worldwide diversity, with an overall heterozygosity of 54% (table 5 and fig. 5). Although the neck regions of both genes share 92% of nucleotide identity, nonuniform mutation rates could, again, explain the patterns observed. However, this does not seem to be the case, since mutation-rate variation should influence the number of alleles observed rather than their frequencies, which are subject either to genetic drift or to natural selection. Indeed, we observed an even higher number of repeat alleles for CD209 (eight alleles) than for CD209L (seven alleles) (table 4 and fig. 5). Overall, differences in genomic forces seem to be insufficient to explain the contrasting patterns observed at both the sequence and neck-region length variation levels; therefore, the action of differential selective pressures acting on these genes becomes the most plausible scenario."}