Analysis of European mtDNAs for recombination

Abstract

The standard paradigm postulates that the human mitochondrial genome (mtDNA) is strictly maternally inherited and that, consequently, mtDNA lineages are clonal. As a result of mtDNA clonality, phylogenetic and population genetic analyses should therefore be free of the complexities imposed by biparental recombination. The use of mtDNA in analyses of human molecular evolution is contingent, in fact, on clonality, which is also a condition that is critical both for forensic studies and for understanding the transmission of pathogenic mtDNA mutations within families. This paradigm, however, has been challenged recently by Eyre-Walker and colleagues. Using two different tests, they have concluded that recombination has contributed to the distribution of mtDNA polymorphisms within the human population. We have assembled a database that comprises the complete sequences of 64 European and 2 African mtDNAs. When this set of sequences was analyzed using any of three measures of linkage disequilibrium, one of the tests of Eyre-Walker and colleagues, there was no evidence for mtDNA recombination. When their test for excess homoplasies was applied to our set of sequences, only a slight excess of homoplasies was observed. We discuss possible reasons that our results differ from those of Eyre-Walker and colleagues. When we take the various results together, our conclusion is that mtDNA recombination has not been sufficiently frequent during human evolution to overturn the standard paradigm.

Figure 1

LD as a function of distance for synonymous polymorphisms in the mtDNA coding region. A total of 11 sites were used for analysis, and these included polymorphisms at nucleotides 5147, 6776, 7028, 8697, 11251, 11467, 11719, 11812, 12372, 12612, and 13368. The r² estimators of LD were calculated as in Awadalla et al. (1999).

Figure 2

LD as a function of distance for all site changes within the mtDNA coding region. In addition to the 11 synonymous polymorphisms analyzed (see fig. 1), this analysis included the 14 sequence changes at nucleotides 709, 930, 1811, 1888, 2706, 3010, 4216, 10398, 10463, 12308, 13708, 14233, 14766, and 14798. These additional sites included nonsynonymous polymorphisms as well as sequence changes in the rRNA and tRNA genes. The data shown here were obtained using the r² measure of LD.

Figure 3

LD as a function of distance for sequence changes in the control region. A total of 15 sites were analyzed, and these included the changes at nucleotides 73, 146, 152, 185, 195, 295, 462, 489, 16069, 16126, 16189, 16294, 16304, 16311, and 16519. The data shown here were obtained using the r² measure of LD.