Abstract
Several recent studies have examined the function and evolution of a Drosophila homolog to the human breast cancer susceptibility gene BRCA2, named dmbrca2. We previously identified what appeared to be a recent expansion in the RAD51-binding BRC-repeat array in the ancestor of Drosophila yakuba. In this study, we examine patterns of variation and evolution of the dmbrca2 BRC-repeat array within D. yakuba and its close relatives. We develop a model of how unequal crossing over may have produced the expanded form, but we also observe short repeat forms, typical of other species in the D. melanogaster group, segregating within D. yakuba and D. santomea. These short forms do not appear to be identical-by-descent, suggesting that the history of dmbrca2 in the D. melanogaster subgroup has involved repeat unit contractions resulting in homoplasious forms. We conclude that the evolutionary history of dmbrca2 in D. yakuba and perhaps in other Drosophila species may be more complicated than can be inferred from examination of the published single genome sequences per species.
Highlights
The human breast cancer susceptibility gene BRCA2 encodes a protein widely studied due to its importance in DNA repair [1,2,3]
Mutations in human germline BRCA2 lead to a lifetime increased susceptibility to breast and ovarian cancers [4,5], perhaps resulting from inefficient repair of DNA double strand breaks (DSBs) during homologous recombination [6,7,8]
There is large variation in repeat number across the phylogeny of Drosophila, this variation appears to be absent within the melanogaster group, in which the species that have published genome sequences all contains 3 BRC repeats. The exception to this pattern in the melanogaster group is D. yakuba, whose published genome sequence of dmbrca2bears five BRC repeats. Observation of this alternate repeat form raises several questions: is this higher repeat number real or a genome mis-assembly artifact [19]? If it is real, is this higher repeat number form ubiquitous across all D. yakuba strains, or is a shorter form present in natural populations? Can we infer the historical change in the number of repeats by analyzing nucleotide sequence? And if there are alternate forms, can we detect evidence for associated natural selection in the spread of the large number repeat form? In this study, we investigate the sequence and evolution of the number of BRC repeats in the Drosophila homolog of BRCA2 in D. yakuba and its sister species D. santomea and place it into an evolutionary context
Summary
The human breast cancer susceptibility gene BRCA2 encodes a protein widely studied due to its importance in DNA repair [1,2,3]. There is large variation in repeat number across the phylogeny of Drosophila, this variation appears to be absent within the melanogaster group, in which the species that have published genome sequences all contains 3 BRC repeats.
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