GENOME EVOLUTION AND THE INSERTION/DELETION SPECTRUM

观察到缺失谱（缺失率和大小分布）

The deletion spectrum (rate and size distribution of deletions) observed in "dead-on-arrival" copies of the LINE element Helena shows an overall rate of DNA loss in Drosophila that is approximately 75 times greater than that found in mammals. These data may have important implications for mutation pressure, the evolutionary persistence of DNA sequences whose presence is not constrained by selection, and possibly for differences in genome size. However, there are a number of problems in extrapolating the Helena data to the entire genome. One possibility is that the Helena element is prone to deletions, and so is not representative of other Drosophila sequences, or even of other LINE elements. Another possibility is that the deletion spectrum of Helena is biased because many copies are present in heterochromatin, and the insertion/deletion (indel) spectrum may differ between heterochromatin and euchromatin. A third possibility is that Helena and other transposable elements have an elevated deletion spectrum owing to the fact that they are middle repetitive DNA, and that single-copy sequences, such as pseudogenes, would have a different indel spectrum. The only way to resolve these issues is by obtaining additional data on other types of sequences in the Drosophila genome. We therefore propose to determine the indel spectrum in the LINE element jockey in species of the D. melanogaster subgroup. These experiments will be carried out in such a way that elements present in euchromatin can be distinguished from those present in heterochromatin. This approach provides a unique opportunity to address the issue of whether the indel spectrum differs between heterochromatin and euchromatin; it also allows a critical test of the "heterochromatic graveyard" hypothesis of Charlesworth, which states that transposable elements are subject to weaker selection in heterochromatin than in euchromatin, and therefore persist longer in heterochromatin. (If true, LINE elements in heterochromatin should be, on the average, older and therefore have more nucleotide substitutions.) We will also study the spectrum of indels, relative to nucleotide substitutions, in two bona fide pseudogenes present in D. melanogaster and other species in the D. melanogaster subgroup, namely, swapsi (a swallow pseudogene) and Lcppsi (a larval citticle protein pseudogene). Analysis of the limited data presently available for these pseudogenes yields inconclusive, and possibly inconsistent, results.