Pattern and process in human genetic diversity: from genomes to populations

This Wellcome-funded Senior Fellowship project (2004-2009) built directly upon work in our previous project 'The Y chromosome as a marker for the history and structure of human populations', aiming to:

• extend and refine the human Y chromosome for use as a phylogeographic tool. We aimed to exploit a new resource of multiple novel microsatellites to define sub-lineages and to estimate, with new precision, time to most recent common ancestor for groups of Y chromosomes. This should allow phylogeographic studies at refined resolution, objective tests of hypotheses about the human past, and will have applications in the study of histories of human genealogies.
• analyse the fundamental and dynamic processes of gene conversion that shape diversity within Y-chromosomal paralogues. Haploidy, a well-characterised phylogeny and a high proportion of paralogous sequences make the Y an ideal system in which to study gene conversion, a poorly understood but important process in patterning human genetic diversity. We aimed to use indirect (phylogenetic) and direct (sperm DNA) methods to study conversion in two classes of Y paralogues - direct repeats, and inverted repeats arranged as 'palindromes', including giant repeats in which mechanisms may have evolved to protect genes essential in spermatogenesis against mutation.
• Based on extensive experience of the Y as a model, but recognising the limitations of evolutionary studies using this single locus, this project has also asked whether the haplotype block structure of the genome allows it to be treated like a set of miniature Y chromosomes, in which historical recombination is absent. We aimed to develop novel and informative phylogeographic SNP- and microsatellite-defined autosomal and X-chromosomal haplotypes, selected using data emerging from the HapMap project, and use these in large-scale population studies. Aims were to establish absence of recombination; construct phylogenies using binary markers, rooting them using chimpanzee sequences; investigate cross-population concordance of haplotype block structures; interpret non-concordance in terms of population history, and possible polymorphism in recombination behaviour; and use microsatellite diversity to estimate TMRCA for haplotypes.

This work aimed to illuminate the fundamental processes of mutation, conversion and recombination, and show how these interact with population processes to pattern human genetic diversity.

For publications emerging so far from this project, please see our main web-page. This project formed the basis for a follow-up Senior Fellowship project, Sex, genomes, history: molecular, evolutionary and cultural effects on human genetic diversity.

Funding

Last updated: 3rd August, 2009
Mark Jobling
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