Abstract
Segmental duplications are an important class of mutations. Because a large proportion of segmental duplications may often be strongly deleterious, high frequency or fixed segmental duplications may represent only a tiny fraction of the mutational input. To understand the emergence and elimination of segmental duplications, we survey polymorphic duplications, including tandem and interspersed duplications, in natural populations of Drosophila by haploid embryo genomes. As haploid embryos are not expected to be heterozygous, the genome, sites of heterozygosity (referred to as pseudoheterozygous sites [PHS]), may likely represent recent duplications that have acquired new mutations. Among the 29 genomes of Drosophila melanogaster, we identify 2,282 polymorphic PHS duplications (linked PHS regions) in total or 154 PHS duplications per genome. Most PHS duplications are small (83.4% < 500 bp), Drosophila melanogaster lineage specific, and strain specific (72.6% singletons). The excess of the observed singleton PHS duplications deviates significantly from the neutral expectation, suggesting that most PHS duplications are strongly deleterious. In addition, these small segmental duplications are not evenly distributed in genomic regions and less common in noncoding functional element regions. The underrepresentation in RNA polymerase II binding sites and regions with active histone modifications is correlated with ages of duplications. In conclusion, small segmental duplications occur frequently in Drosophila but rapidly eliminated by natural selection.