PMC:1271393 / 47576-51314 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1271393","sourcedb":"PMC","sourceid":"1271393","source_url":"https://www.ncbi.nlm.nih.gov/pmc/1271393","text":"In clear contrast to its homologue, CD209L presented extremely elevated nucleotide-diversity levels. High levels of diversity can result either from a relaxation of the functional constraint, which allows the stochastic accumulation of new mutations, or from the action of balancing selection, which maintains over time two or more functionally different alleles (and all linked variation) at intermediate frequencies. Several lines of evidence lend support to the selective hypothesis. First, if CD209L nucleotide diversity has been driven by the action of balancing selection, population-genetics relationships would have been accordingly altered. In this context, diversity studies in neutral, or assumedly neutral, regions of the genome—such as the Y chromosome (Underhill et al. 2000; Hammer et al. 2001; Jobling and Tyler-Smith 2003), mtDNA (Wallace et al. 1999; Ingman et al. 2000; Mishmar et al. 2003), Alu insertions (Watkins et al. 2001), as well as some autosomal genes (Stephens et al. 2001; Akey et al. 2004)—showed that African populations are genetically more diverse than are non-Africans, an observation generally interpreted as a support of the “Out of Africa” model for the origin of modern humans (Lewin 1987). For CD209L, even if we observed 1.5 times more segregating sites in African than in non-African populations, as indicated by the higher θw value found in Africa, similar values of nucleotide diversity were detected in the three groups, with Europeans presenting even higher π values than do Africans. This unusual scenario, which is at odds with neutral expectations, has already been described for other regions of the genome, such as the β-globin gene and the 5′cis-regulatory region of CCR5, for which the action of balancing selection has been convincingly proposed (Harding et al. 1997; Bamshad et al. 2002). Second, balancing selection tends to increase within-population diversity while decreasing F ST, compared with neutrally evolving loci (Cavalli-Sforza 1966; Harpending and Rogers 2000; Akey et al. 2002; Bamshad and Wooding 2003; Cavalli-Sforza and Feldman 2003). Indeed, our data are compatible with these predictions, since the 5%F ST value observed for CD209L is threefold lower than that estimated for CD209 (15%) and is similar to that found, for example, for the bitter-taste receptor gene (5.6%), for which there is compelling evidence of balancing-selection action (Wooding et al. 2004). Third, results of our Tajima's D analysis were significantly positive for European and East Asian populations, because of the skew of CD209L frequency spectrum toward an excess of intermediate-frequency alleles (table 2), a pattern that further supports the action of balancing selection. However, since the null model used to assess significance makes unrealistic assumptions about past population demography (i.e., constant population sizes), the rejection of the standard neutral model cannot be interpreted as unambiguous evidence of selection. Indeed, the observation that only non-African populations showed a significant departure from neutrality raises the question of whether these patterns could have resulted instead from the bottleneck that occurred during the Out of Africa exodus. A way to circumvent this conundrum is to analytically integrate the fact that demography affects all the genome equally, whereas selection directs its effects toward specific loci. Thus, to correct for the confounding effects of demography, we plotted our results against the empirical distributions of Akey et al. (2004) for Tajima's D statistics. Our values remained significant for CD209L, which therefore reinforces the idea that the pattern observed is unlikely to be the sole result of demography.","tracks":[{"project":"2_test","denotations":[{"id":"16252244-11062480-2049656","span":{"begin":784,"end":788},"obj":"11062480"},{"id":"16252244-11420360-2049657","span":{"begin":804,"end":808},"obj":"11420360"},{"id":"16252244-12897772-2049658","span":{"begin":834,"end":838},"obj":"12897772"},{"id":"16252244-10570998-2049659","span":{"begin":863,"end":867},"obj":"10570998"},{"id":"16252244-11130070-2049660","span":{"begin":883,"end":887},"obj":"11130070"},{"id":"16252244-12509511-2049661","span":{"begin":904,"end":908},"obj":"12509511"},{"id":"16252244-11179020-2049662","span":{"begin":942,"end":946},"obj":"11179020"},{"id":"16252244-11452081-2049663","span":{"begin":998,"end":1002},"obj":"11452081"},{"id":"16252244-15361935-2049664","span":{"begin":1016,"end":1020},"obj":"15361935"},{"id":"16252244-3114877-2049665","span":{"begin":1224,"end":1228},"obj":"3114877"},{"id":"16252244-9106523-2049666","span":{"begin":1817,"end":1821},"obj":"9106523"},{"id":"16252244-12149450-2049667","span":{"begin":1838,"end":1842},"obj":"12149450"},{"id":"16252244-4379525-2049668","span":{"begin":1996,"end":2000},"obj":"4379525"},{"id":"16252244-11701634-2049669","span":{"begin":2024,"end":2028},"obj":"11701634"},{"id":"16252244-12466284-2049670","span":{"begin":2042,"end":2046},"obj":"12466284"},{"id":"16252244-12560807-2049671","span":{"begin":2068,"end":2072},"obj":"12560807"},{"id":"16252244-12610536-2049672","span":{"begin":2101,"end":2105},"obj":"12610536"},{"id":"16252244-14997422-2049673","span":{"begin":2433,"end":2437},"obj":"14997422"},{"id":"16252244-15361935-2049674","span":{"begin":3551,"end":3555},"obj":"15361935"}],"attributes":[{"subj":"16252244-11062480-2049656","pred":"source","obj":"2_test"},{"subj":"16252244-11420360-2049657","pred":"source","obj":"2_test"},{"subj":"16252244-12897772-2049658","pred":"source","obj":"2_test"},{"subj":"16252244-10570998-2049659","pred":"source","obj":"2_test"},{"subj":"16252244-11130070-2049660","pred":"source","obj":"2_test"},{"subj":"16252244-12509511-2049661","pred":"source","obj":"2_test"},{"subj":"16252244-11179020-2049662","pred":"source","obj":"2_test"},{"subj":"16252244-11452081-2049663","pred":"source","obj":"2_test"},{"subj":"16252244-15361935-2049664","pred":"source","obj":"2_test"},{"subj":"16252244-3114877-2049665","pred":"source","obj":"2_test"},{"subj":"16252244-9106523-2049666","pred":"source","obj":"2_test"},{"subj":"16252244-12149450-2049667","pred":"source","obj":"2_test"},{"subj":"16252244-4379525-2049668","pred":"source","obj":"2_test"},{"subj":"16252244-11701634-2049669","pred":"source","obj":"2_test"},{"subj":"16252244-12466284-2049670","pred":"source","obj":"2_test"},{"subj":"16252244-12560807-2049671","pred":"source","obj":"2_test"},{"subj":"16252244-12610536-2049672","pred":"source","obj":"2_test"},{"subj":"16252244-14997422-2049673","pred":"source","obj":"2_test"},{"subj":"16252244-15361935-2049674","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ecbb93","default":true}]}]}}