Evolution of an MCM Complex in Flies That Promotes Meiotic Crossovers by Blocking BLM Helicase

Science  07 Dec 2012:
Vol. 338, Issue 6112, pp. 1363-1365
DOI: 10.1126/science.1228190

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Swapping Recombination Proteins

Crossing over is a means by which organisms create genetic diversity through the mixing of gene complexes. The primary meiotic crossover pathway in budding yeast, mice, nematodes, and plants requires the Msh4–Msh5 heterodimer, which promotes crossovers by blocking anticrossover activities of the Bloom syndrome helicase. However, some fly species, including members of the genus Drosophila, have lost Msh4–Msh5. Kohl et al. (p. 1363) now show that Drosophila have evolved a minichromosome maintenance (MCM)–like protein, dubbed mei-MCM, that performs the same function as Msh4–Msh5. Furthermore, these genes appear to have evolved under positive selection, possibly as a result of their repurposing to this novel function.


Generation of meiotic crossovers in many eukaryotes requires the elimination of anti-crossover activities by using the Msh4-Msh5 heterodimer to block helicases. Msh4 and Msh5 have been lost from the flies Drosophila and Glossina, but we identified a complex of minichromosome maintenance (MCM) proteins that functionally replace Msh4-Msh5. We found that REC, an ortholog of MCM8 that evolved under strong positive selection in flies, interacts with MEI-217 and MEI-218, which arose from a previously undescribed metazoan-specific MCM protein. Meiotic crossovers were reduced in Drosophila rec, mei-217, and mei-218 mutants; however, removal of the Bloom syndrome helicase (BLM) ortholog restored crossovers. Thus, MCMs were co-opted into a novel complex that replaced the meiotic pro-crossover function of Msh4-Msh5 in flies.

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