The Genom of Homo sapiens.pdf

Inferring Human History: Clues fromY-Chromosome HaplotypesP.A. UNDERHILLDepartment of Genetics, Stanford University School of Medicine, Stanford, California 94305-5120DNA molecules are organic elements of informationstorage imbued with imperfect copying processes. Thus,they are fundamental repositories of an organism’s evolutionaryhistory. The field of human molecular evolutionis predicated on the concept that patterns of DNA sequencevariation in living populations encode aspects ofhuman heritage shaped by a constellation of evolutionaryinfluences. The framework of genetic variability in thegenome reflects both evolutionary adaptive processesthat are locus-specific and population-level forces that affectall the components of the genome equally. Geneticresearch often focuses on distinguishing inconsistenciesin patterns of variation between genomic regions to helpbridge the gap between particular genes and traits, includingmatters of function and malfunction. Alternatively,genomic DNA is also an archive of those aspectsof human evolutionary processes reflective of population-levelforces like drift, subdivision, size fluctuation,and migration. By studying the degree of genetic molecularvariation, one can, in principle, reconstruct pastevents such as expansions and settlements from whichorigins of specific populations can be predicted (Cavalli-Sforza et al. 1994). However, since the bulk of commonvariation in the genome occurs between individuals, thedifference between populations is low, making it morechallenging to investigate ambiguities concerning affinitiesand origins of populations. It is the component of between-populationvariance that best provides insights intothe evolution of the spectrum of extant populations (Cavalli-Sforzaand Feldman 2003). In addition, determiningthe migratory patterns of our ancestors and their timing,as well as the amount of population admixture due to suchmigrations, has been experimentally less tractable. Consequently,such issues are often simply ignored when reconstructingpopulation phylogenies where little or nomigration is implicitly assumed.Progress in understanding the spectrum of humanDNA sequence variation and its causes, especially whenintegrated with other knowledge from historians, archaeologists,anthropologists, and linguists, can help recapitulatehuman population histories (Owens and King 1999;Cann 2001). In particular, informative haplotypes, immunefrom the scrambling effects of recurrent mutationand recombination, provide a promising way forward. Inthe early genetic studies, both protein and matrilineal inheritedmitochondrial DNA (mtDNA) loci have providedmuch of the initial evidence. However, considerable recentprogress in elucidating Y-chromosome sequencevariation from the nonrecombining region (NRY) hasmade it possible to more fully investigate the parallel paternalheritage that underlies the central theme of this paper.Although extrapolating variation associated with asingle gene to population history must be done cautiously,the phylogeographic reconstruction of haplotypesoffers one such interpretation that is amenable to testingby further studies from a number of disciplines. Althoughnongenetic evidence provides constraints that improveconfidence in phylogeographic-based interpretations, thedevelopment of statistical methods to objectively evaluatesuch geographic and phylogenetic patterns remainsincomplete (Knowles and Maddison 2002). The growingaccumulation of Y-chromosome haplotype data in geographiccontext will provide a substantial test bed for futurestatistical modeling.Y-CHROMOSOME HAPLOTYPESCONVEY SPATIAL AND TEMPORALINFORMATIONAlthough explorations into prehistory have been traditionallyarcheological, additional perspectives have beenprovided by linguistic and genetic studies. Although therecords of these nonrecombining sex-specific loci maydiverge because of natural selection or differences betweenmale and female behaviors, the accumulation of sequencevariation during the lineal life spans of these haplotypicsystems provides a powerful way to recovergenetic prehistory. Specifically, the particular distinctiveclinal patterns of NRY haplotypes, together with patternsof associated genetic diversification with geography,mark trajectories of gene flow (and by inference, themovement of populations). The lower effective populationsize of Y chromosomes relative to other componentsof the human genome make the Y chromosome particularlysensitive to the influences of drift and founder effect.Whatever the causes of this property (e.g., localized naturalselection, gender-based differential reproductivesuccess, and/or migratory behavior), it is particularly usefulsince it explains the characteristic high stratificationof NRY diversity with geography relative to other genesincluding mtDNA. Although nearly all Y chromosomeshave shared common ancestry, the succession of accumulatinggenetic markers reveals a cascade of differentiationthat randomly coincides with various populationCold Spring Harbor Symposia on Quantitative Biology, Volume LXVIII. © 2003 Cold Spring Harbor Laboratory Press 0-87969-709-1/04. 487