Molecular Population Genetics of Drosophila Subtelomeric DNA

Abstract

DNA sequence surveys in yeast and humans suggest that the forces shaping telomeric polymorphism and divergence are distinctly more dynamic than those in the euchromatic, gene-rich regions of the chromosomes. However, the generality of this pattern across outbreeding, multicellular eukaryotes has not been determined. To characterize the structure and evolution of Drosophila telomeres, we collected and analyzed molecular population genetics data from the X chromosome subtelomere in 58 lines of North American Drosophila melanogaster and 29 lines of African D. melanogaster. We found that Drosophila subtelomeres exhibit high levels of both structural and substitutional polymorphism relative to linked euchromatic regions. We also observed strikingly different patterns of variation in the North American and African samples. Moreover, our analyses of the polymorphism data identify a localized hotspot of recombination in the most-distal portion of the X subtelomere. While the levels of polymorphism decline sharply and in parallel with rates of crossing over per physical length over the distal first euchromatic megabase pairs of the X chromosome, our data suggest that they rise again sharply in the subtelomeric region (%80 kbp). These patterns of historical recombination and geographic differentiation indicate that, similar to yeast and humans, Drosophila subtelomeric DNA is evolving very differently from euchromatic DNA. P OPULATION geneticists aspire to understand the evolutionary forces shaping patterns of molecular polymorphism and divergence. The recent increase in the quantity of DNA sequence data from proteincoding regions has led to considerable advances in our understanding of the forces governing the evolution of such regions. For example, genomic surveys have revealed functional variants as well as classes of genes enriched for the signature of natural selection (e.g., Bustamante et al. 2005;Nielsen et al. 2005;Begun et al. 2007). In contrast, regions of the genome containing fewer genes but an increased density of repetitive sequences have been less amenable to population and molecular evolutionary analysis. These regions, typically found adjacent to telomeres and centromeres, are collectively referred to as the heterochromatin. Because heterochromatic DNA is difficult to clone, sequence, and assemble, much less is known about the structure of these regions. Thus, there is almost no foundation for effective population or comparative genomic analyses. Indeed, only recently have researchers begun to identify the sparsely distributed protein-coding sequences embedded in heterochromatin (reviewed in Yasuhara and Wakimoto 2006).Most population and molecular evolutionary surveys from telomeric regions come from yeast and primates (but see recent work on Arabidopsis in Kuo et al. 2006). These studies show that telomeric DNA is evolving very differently from the gene-rich euchromatin. For example, the telomeric regions of several human chromosomes are dramatically different from the corresponding regions in c...

Recurrent Deletion and Gene Presence/Absence Polymorphism: Telomere Dynamics Dominate Evolution at the Tip of 3L inDrosophila melanogasterandD. simulans

“…Remarkably, levels of nucleotide heterozygosity in the euchromatic sequence adjacent to the subtelomeric deletions were severely reduced compared to levels observed in regions of normal crossing over. A similar pattern was recently reported for the X chromosome (Anderson et al 2008). The fact that nucleotide divergence between species is typical (or slightly elevated) relative to that observed throughout most of the genome supports the idea that reduced nucleotide heterozygosity is a result of linked selection.…”

“…Using the mafNets that underlie this track, we find that in the 50-kb region surrounding mthl8 (chr 3L: 2903-52,902), $89% of bases are aligned after accounting for repeat masking. Using the droSim1 assembly from UCSC, D. simulans orthologs of mthl8 and Lsp1g regions used in our polymorphism resequencing survey could be found, but no obvious D. simulans orthologs of the intergenic f25 and f72 loci were detected, which suggests an unusually high rate of indel divergence in this genomic region, similar to what was observed in the subtelomeric sequence of the X chromosome (Anderson et al 2008). The conservation track in Figure 1 demonstrates this visually.…”

“…0.1; yellow, 0.05 , P , 0.1; red, P , 0.05. yeast, and humans (Broun et al 1992;Caenorhabditis elegans Sequencing Consortium 1998;Vergnaud 1999;Winzeler et al 2003). The data reported here and in Anderson et al (2008) show that Drosophila, too, can be added to the list of organisms harboring extensive variation near the tips of chromosomes. The unique repetitive structure of telomeres, which plays a role in replicating the ends of linear chromosomes, is likely to be responsible for this extensive brand of genetic variation.…”

“…The distal region of the Drosophila melanogaster X chromosome shows reduced levels of heterozygosity but relatively low levels of linkage disequilibrium (LD) (Begun and Aquadro 1995;Langley et al 2000). The analysis of the tip of the X chromosome has recently been extended to the subtelomeric sequences, which show rapid divergence, including high levels of insertions and deletions, low heterozygosity, and evidence of extensive recombination (Anderson et al 2008). Here we report on an unusual case of gene presence/absence variation in D. melanogaster and D. simulans.…”

Segregation distortion in chicken and the evolutionary consequences of female meiotic drive in birds

“…Overall, the potential for telomere drive has been explored relatively little, despite early observations in Drosophila showing that distally located chromosomal elements have the ability to alter a chromosome's chances of inclusion in the egg (Novitski, 1951). Indirectly, observations of high rates of subtelomeric sequence turnover in both Drosophila and primates (Anderson et al, 2008) and frequent selective sweeps in human subtelomeric regions (Hellmann et al, 2008) may reflect the action of telomere drive. In addition, if drive at telomeres and centromeres confer similar, negative, fitness consequences, an evolutionary dynamics between telomere sequence and telomere binding proteins, analogous to that described in the Genomic Conflict Theory for centromers, might develop.…”