DNA sequence variation in a non-coding region of low recombination on the human X chromosome

DNA sequence variation has become a major source of insight regarding the o rigin and history of our species(1-5) as well as an important tool for the identification of allelic variants associated with disease. Comparative seq uencing of DNA has to date focused mainly on mitochondrial (mt) DNA, which due to its apparent lack of recombination and high evolutionary rate lends itself well to the study of human evolution(1). These advantages also entai l limitations. For example, the high mutation rate of mtDNA results in mult iple substitutions that make phylogenetic analysis difficult and, because m tDNA is maternally inherited, it reflects only the history of females. For the history of males, the non-recombining part of the paternally inherited Y chromosome can be studied(2). The extent of variation on the Y chromosome is so low that variation at particular sites known to be polymorphic rathe r than entire sequences are typically determined(6). It is currently unclea r how some forms of analysis (such as the coalescent) should be applied to such data, Furthermore, the lack of recombination means that selection at a ny locus affects all 59 Mb of DNA. To gauge the extent and pattern of point substitutional variation in non-coding parts of the human genome, we have sequenced 10 kb of non-coding DNA in a region of low recombination at Xq13. 3. Analysis of this sequence in 69 individuals representing all major lingu istic groups reveals the highest overall diversity in Africa, whereas deep divergences also exist in Asia. The time elapsed since the most recent comm on ancestor (MRCA) is 535.000+/-119.000 years, We expect this type of nucle ar locus to provide more answers about the genetic origin and history of hu mans.