Messages through Bottlenecks: On the Combined Use of Slow and Fast Evolving Polymorphic Markers on the Human Y Chromosome

Abstract

In 1995, much to the delight of mitochondrial Eve (Cann et al. 1987), the search for a suitable partner resulted in the discovery of Y-chromosomal Adam (Dorit et al. 1995; Paabo 1995). Like Eve, he was traced back to sub-Saharan Africa, although with a date of 270,000 years ago, he seems a bit older than she. On the basis of the absence of sequence variation in a part of the ZFY gene in 38 globally dispersed male subjects, this date was not undisputed (Donnelly et al. 1996; Fu and Li 1996; Rogers et al. 1996; Weiss and von Haeseler 1996). Later in the same year, two additional studies did reveal a limited number of sequence variants on other parts of the Y chromosome. Because of these variants, estimates were obtained of the times back to our most recent common (male) ancestor of 37,000–49,000 years ago (Whitfield et al. 1995) and of 51,000–411,000 years ago (Hammer 1994). Now, just 5 years later, with simple PCR strategies, ⩾250 polymorphic loci scattered over the entire nonrecombining part of the human Y chromosome can be identified. Among these polymorphisms are (1) biallelic markers with a low mutation rate representing unique (or near-unique) mutation events (UMEs) in human evolution, such as single base-pair substitutions (Underhill et al. 1997), an ALU insertion/deletion polymorphism (Hammer 1994), or a LINE insertion (Santos et al. 2000); (2) moderately fast-evolving microsatellites or simple-tandem repeats (STRs), with an average mutation frequency of ∼.2% per generation (Heyer et al. 1997; Jobling et al. 1999; Kayser et al. 2000); and (3) fast-evolving loci, such as the minisatellite locus MSY1 (Jobling et al. 1998) with a mutation frequency of 6%–11% per generation. With the exception of the two pseudoautosomal regions, the almost 60–Mb nonrecombining part of the Y chromosome is transmitted strictly from father to son without recombination (Jobling and Tyler-Smith 1995). This renders the Y chromosome probably the most versatile haplotypic genotyping system of the human genome. It is thus not surprising that chromosome-Y polymorphisms have been used to follow the migration patterns of our male ancestors from the recent past (Heyer et al. 1997; Foster et al. 1998) through historical times (Skorecki et al. 1997; Hammer et al. 2000), to the origins of modern humans (Hammer et al. 1998). Recently, two excellent review articles featuring the Y chromosome were published. The first (Bertranpetit 2000) addresses the difficulties of reliably tracing back human origins solely on the basis of Y-chromosomal UMEs. The second (Jobling and Tyler-Smith 2000) gives a detailed discussion of many genetic aspects of the Y chromosome in the context of disease and selection. This editorial will be restricted to the combined use of UMEs and STRs on the Y chromosome to reconstruct our genetic history. This application has received considerable attention in recent articles published in this journal and elsewhere (see, e.g., Zerjal et al. 1997; Bianchi et al. 1998; Hurles et al. 1998, 1999; Kittles et al. 1998; Bosch et al. 1999; Karafet et al. 1999; Lahermo et al. 1999; Ruiz-Linares et al. 1999; Helgason et al. 2000b; Hill et al. 2000; Santos et al. 2000). That the combined use of Y-chromosomal UMEs and STRs is not without any caveats will be explained below.