Concurrent Duplication of Drosophila Cid and Cenp-C Genes Resulted in Accelerated Evolution and Male Germline-Biased Expression of the New Copies

Abstract

Despite their essential role in the process of chromosome segregation in eukaryotes, kinetochore proteins are highly diverse across species, being lost, duplicated, created, or diversified during evolution. Based on comparative genomics, the duplication of the inner kinetochore proteins CenH3 and Cenp-C, which are interdependent in their roles of establishing centromere identity and function, can be said to be rare in animals. Surprisingly, the Drosophila CenH3 homolog Cid underwent four independent duplication events during evolution. Particularly interesting are the highly diverged Cid1 and Cid5 paralogs of the Drosophila subgenus, which are probably present in over one thousand species. Given that CenH3 and Cenp-C likely co-evolve as a functional unit, we investigated the molecular evolution of Cenp-C in species of Drosophila. We report yet another Cid duplication (leading to Cid6) within the Drosophila subgenus and show that not only Cid, but also Cenp-C is duplicated in the entire subgenus. The Cenp-C paralogs, which we named Cenp-C1 and Cenp-C2, are highly divergent. Both Cenp-C1 and Cenp-C2 retain key motifs involved in centromere localization and function, while some functional motifs are conserved in an alternate manner between the paralogs. Interestingly, both Cid5 and Cenp-C2 are male germline-biased and evolved adaptively. However, it is currently unclear if the paralogs subfunctionalized or if the new copies acquired a new function. Our findings point towards a specific inner kinetochore composition in a specific context (i.e., spermatogenesis), which could prove valuable for the understanding of how the extensive kinetochore diversity is related to essential cellular functions.

Centromere structure and function: lessons from Drosophila

“…2018 ). Interestingly, the cenp-c gene was also found to have duplicated during evolution, something that was probably expected, given its association with Cal1 and dCENP-A ( Rosin and Mellone 2016 ; Teixeira et al . 2018 ).…”

“…2012 ; Rosin and Mellone 2016 ; Kursel and Malik 2017 ). While, in melanogaster , dCENP-A is encoded by a single copy gene, two recent studies have reported that in other species, there have been five independent duplications of the genes during evolution, with the products retaining their centromeric localization but seems that their functions might be nonredundant, while some are expressed primarily in the male germline ( Kursel and Malik 2017 ; Teixeira et al . 2018 ).…”

“…2018 ). Like some of the cid genes, one cenp-c duplication product also presents a male bias, raising the exciting possibility that kinetochore structure is diverse in specific contexts ( Teixeira et al . 2018 ).…”

Adaptations for centromere function in meiosis

“…Species from the Sophophora subgenus typically express three of them (Cid1, Cid3, and Cid4), whereas the Drosophila subgenus expresses two paralogs (Cid1 and Cid5). More recently, a novel Cid duplication was described for the Drosophila subgenus (Cid6) [56]. All the variants tested in D. auraria show centromeric localization, suggesting that all retained centromeric function [51].…”

“…After the duplication, one of the genes can assume more specialized functions, whereas the other one still performs its initial role. Interestingly, CENP-A duplicates differ mostly in the N-terminal tail sequence [51][52][53][54][55][56].…”