Integrated analysis of sequence evolution and population history using hypervariable compound haplotypes

We have examined compound haplotypes from a highly informative region of hu man chromosome 16, in which information from the rapid evolution of a highl y unstable minisatellite is integrated with data on the longer-term evoluti on of this segment from 10 flanking substitutional polymorphisms, Combined with sequence data from non-human primates, analysis of relationships betwe en these compound haplotypes allows the reconstruction of a rooted network of the evolutionary pathways between them, Most relationships can be explai ned via simple substitutional mutations, although the origins of some haplo types involve recurrent events at a hotspot for substitutional mutation and /or gene conversion. For compound haplotypes including the minisatellite ar ray, the network found in a range of world-wide populations constitutes a h ighly informative data set for the analysis of population history (437 diff erent compound haplotypes were discriminated among 658 studied). Since the mutation rates and processes of the minisatellite array are known from dire ct studies, ages for individual lineages have been estimated using associat ed minisatellite diversity, These analyses suggest that the higher informat ion content and sampling depth of these compound haplotypes may allow more precise calibration of lineage ages than is possible using coalescent analy sis of DNA sequence. Using this method we have dated the oldest Eurasian li neage as 52 000-66 000 years and the oldest European specific lineage as 37 600-56 200 years.