Academic journal article Genetics

Microsatellite Length Differences between Humans and Chimpanzees at Autosomal Loci Are Not Found at Equivalent Haploid Y Chromosomal Loci

Academic journal article Genetics

Microsatellite Length Differences between Humans and Chimpanzees at Autosomal Loci Are Not Found at Equivalent Haploid Y Chromosomal Loci

Article excerpt

ABSTRACT

When homologous microsatellites are compared between species, significant differences in mean length are often noted. A dominant cause of these length differences is ascertainment bias due to selection for maximum repeat number and repeat purity when the markers are being developed. However, even after ascertainment bias has been allowed for through reciprocal comparisons, significant length differences remain, suggesting that the average microsatellite mutation rate differs between species. Two classes of mechanism have been proposed: rapid evolution of enzymes involved in the generation and repair of slippage products (enzyme evolution model) and heterozygote instability, whereby interchromosomal events at heterozygous sites offer extra opportunities for mutations to occur (heterozygote instability model). To examine which of these hypotheses is most likely, we compared ascertainment bias and species length differences between humans and chimpanzees in autosomal and Y chromosomal microsatellites.We find that levels of ascertainment bias are indistinguishable, but that interspecies length differences are significantly greater for autosomal loci compared with haploid Y chromosomal loci. Such a pattern is consistent with predictions from the heterozygote instability model and is not expected under models of microsatellite evolution that do not include interchromosomal events such as the enzyme evolution model.

MICROSATELLITES are sequences of repeated short (1-5 bp) motifs used commonly as genetic markers due to their high levels of slippage-generated repeat copy number variation (LEVINSON and GUTMAN 1987; SCHLÖTTERER and TAUTZ 1992). However, despite intense study, many aspects of microsatellite evolution remain unresolved. For example, although most mutations involve the gain or loss of a single repeat unit, some studies report a tendency for gains in length to outnumber losses (AMOS et al. 1996; KAYSER et al. 2000; DUPUY et al. 2004), while others report either unbiased mutations (BRINKMANN et al. 1998; XU et al. 2000) or a tendency to decline in length (SAJANTILA et al. 1999) especially among very long microsatellites (XU et al. 2000; HUANG et al. 2002). Mutation rates and other properties appear to depend critically on the structure of the microsatellite, with repeat number and the degree of interruption both being important (BRINKMANN et al. 1998; KAYSER et al. 2000, 2004;HUANG et al. 2002). Such structural variation may help to explain the contradictory nature of some of these studies (for overview see ELLEGREN 2004).

An alternative view on the mutation process can be gained by exploiting the fact that primer sets designed for one species often amplify homologous loci in related species, a process referred to as cross-species amplification. Early studies using this approach found an unexpected pattern in whichmicrosatellites in one species were often consistently longer than their homologs in a related species. Thus, human microsatellites are usually longer than their chimpanzee homologs (RUBINSZTEIN et al. 1995; AMOS and RUBINSZTEIN 1996; AMOS et al. 1996), microsatellites in sheep are longer than in cows (CRAWFORD et al. 1998), and barn swallow loci are longer than in other related birds (PRIMMER and ELLEGREN 1998).

Unfortunately, length comparisons between species are complicated by an ascertainment bias (ELLEGREN et al. 1995, 1997; ZHU et al. 2000; WEBSTER et al. 2002; AMOS et al. 2003). During marker development, highly polymorphic loci are normally preferred and, since the degree of polymorphism and microsatellite length are positively correlated (e.g., KAYSER et al. 2004), this usually means that loci are chosen to be as long as possible in the target species. As a consequence, there is a tendency for markers to be longer and thus more polymorphic in the species from which they were originally cloned, relative to homologous products in related species they are applied to. …

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