Slip-sliding away: serial changes and homoplasy in repeat number in the Drosophila yakuba homolog of human cancer susceptibility gene BRCA2

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.

Figure 1. Phylogenetic tree of sequenced Drosophila species.

This tree presents the number of “BRC” repeats from the published genome sequence for each species in the genus Drosophila. The blue box highlights the melanogaster group, which has a pattern of apparent stability in repeat number.

Figure 2. Neighbor joining tree created from individual dmbrca2 BRC repeats from published genome sequences.

Sequences included are derived from Drosophila melanogaster (Dme), D. yakuba (Dya), D. sechellia (Dse), D. erecta (Der), and D. simulans (Dsi). Dya3c and Dya3n indicate 5′ and 3′ regions of repeat 3, respectively.

Figure 3. Amino acid sequences from individual dmbrca2 BRC repeat units across Drosophila species.

These amino acid translations from the published genome sequences of Drosophila melanogaster (Dmel), D. yakuba (Dya), D. sechellia (Dse), D. erecta, and D. simulans (Dsi) are aligned and color coded to highlight the similarities between them. D. yakuba repeat 3 (Dya3) is split into two halves that seem to group as follows, the 3′ end with the 1st repeats and the 5′ end with the 3rd repeats.

Figure 4. Schematic of possible unequal crossover event and a hypothetical phylogenetic tree showing when it could have occurred.

Figure 5. Aligned amino acid sequences showing the different forms of the Drosophila 2nd BRC repeat.

These amino acid translations are from Dya2, Dya4, D. yakuba strains Cascade24 and Cascade 21, D. santomea strains STO7 and LAGO1482, Der and Dme. The asterisks above the alignment indicate sites that have differences between the published genome sequences Dya2 and Dya4, but are not fixed among the sequenced 5-repeat strains of D. yakuba (suggesting they are not “diagnostic”).