Academic journal article Genetics

Multiple Signatures of Positive Selection Downstream of Notch on the X Chromosome in Drosophila Melanogaster

Academic journal article Genetics

Multiple Signatures of Positive Selection Downstream of Notch on the X Chromosome in Drosophila Melanogaster

Article excerpt

ABSTRACT

To identify genomic regions affected by the rapid fixation of beneficial mutations (selective sweeps), we performed a scan of microsatellite variability across the Notch locus region of Drosophila melanogaster. Nine microsatellites spanning 60 kb of the X chromosome were surveyed for variation in one African and three non-African populations of this species. The microsatellites identified an ~14-kb window for which we observed relatively low levels of variability and/or a skew in the frequency spectrum toward rare alleles, patterns predicted at regions linked to a selective sweep. DNA sequence polymorphism data were subsequently collected within this 14-kb region for three of the D. melanogaster populations. The sequence data strongly support the initial microsatellite findings; in the non-African populations there is evidence of a recent selective sweep downstream of the Notch locus near or within the open reading frames CG18508 and Fcp3C. In addition, we observe a significant McDonald-Kreitman test result suggesting too many amino acid fixations species wide, presumably due to positive selection, at the unannotated open reading frame CG18508. Thus, we observe within this small genomic region evidence for both recent (skew toward rare alleles in non-African populations) and recurring (amino acid evolution at CG18508) episodes of positive selection.

THE observed positive correlation between nucleotide diversity and the rate of crossing over at a locus in Drosophila melanogaster (BEGUN and AQUADRO 1992) raised the possibility that within this species, the fixation of advantageous mutations has been frequent. The role of mutation in shaping the correlation has been rejected for Drosophila (no relationship between divergence and recombination; BEGUN and AQUADRO 1992). However, the relative roles of positive selection vs. the continuous removal of deleterious mutations ("background selection"; CHARLESWORTH et al. 1993; HUDSON and KAPLAN 1995) are still debated (see ANDOLFATTO 2001a and AQUADRO et al. 2001). Attempts to distinguish between these forces have led to results that are mixed or difficult to interpret (e.g., AQUADRO et al. 1994; BEGUN and WHITLEY 200Oa; LANGLEY et al. 2000; ANDOLFATTO 2001a,b; NACHMAN 2001; KAUER et al. 2002; SCHÔFL and SCHLÔTTERER 2004).

While this debate continues, a growing number of studies show that positive selection has affected molecular evolution at specific genomic regions within D. melanogaster. These studies have largely been conducted at loci for which there were a priori expectations that advantageous fixations had occurred. Recent examples of such loci in Drosophila are Pgm (VERRELLI and EANES 2000), Relish (BEGUN and WHITLEY 200Ob), mth (SCHMIDT et al. 2000; DUVERNELL et al. 2003), desat2 (TAKAHASHI et al. 2001), and immunity-related proteins (SCHLENKE and BEGUN 2003).

These results have motivated scans of the genome for patterns and levels of variability at multiple microsatellites and/or short segments of nucleotide sequence that might indicate recent positive selection (see review by SCHLOTTERER 2002a). The premise is that markers closest to the target of a sweep would show a reduction of variability and/or a nonequilibrium allele frequency distribution (depending on the strength of selection, time since the sweep, and regional rates of recombination; e.g., KAPLAN et al. 1989). Genome scans have been preformed in two ways. Some studies are based on coarse large-scale chromosomal or genome-wide scans of variation (e.g., SCHLOTTERER 2002b; PAYSEUR et al. 2002; GLINKA et al. 2003; KAUER et al. 2003; KAYSER et al. 2003; ORENGO and AGUADÉ 2004; STORZ et al. 2004). Others are based on genotyping markers in spécifie genomic regions. The primary goal of these studies is to localize, on a much finer scale, the specific targets of positive selection (KoHN et al. 2000; NURMINSKY et al. 2001; HARR et al. 2002; SCHLENKE and BEGUN 2004). Studies of this sort should shed light onto the types of genetic changes that have resulted in fitness differences within and between species. …

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