Recurrent gene duplication leads to diverse repertoires of centromeric histones in Drosophila species
Authors: Kursel Lisa E. , Malik Harmit S. 
Published: November 2016

Despite their essential role in the process of chromosome segregation in most eukaryotes, centromeric histones show remarkable evolutionary lability. Not only have they been lost in multiple insect lineages, but they have also undergone gene duplication in multiple plant lineages. Based on detailed study of a handful of model organisms includingDrosophilamelanogaster, centromeric histone duplication is considered to be rare in animals. Using a detailed phylogenomic study, we find thatCid, the centromeric histone gene, has undergone four independent gene duplications during Drosophila evolution. We find duplicateCidgenes inD. eugracilis(Cid2), in themontiumspecies subgroup (Cid3, Cid4) and in the entireDrosophilasubgenus (Cid5). We show that Cid3, Cid4, Cid5 all localize to centromeres in their respective species. SomeCidduplicates are primarily expressed in the male germline. With rare exceptions,Cidduplicates have been strictly retained after birth, suggesting that they perform non-redundant centromeric functions, independent from the ancestralCid. Indeed, each duplicate encodes a distinct N-terminal tail, which may provide the basis for distinct protein-protein interactions. Finally, we show some Cid duplicates evolve under positive selection whereas others do not. Taken together, our results support the hypothesis thatDrosophilaCid duplicates have subfunctionalized. Thus, these gene duplications provide an unprecedented opportunity to dissect the multiple roles of centromeric histones.

Author Summary

Centromeres ensure faithful segregation of DNA throughout eukaryotic life, thus providing the foundation for genetic inheritance. Paradoxically, centromeric proteins evolve rapidly despite being essential in many organisms. We have previously proposed that this rapid evolution is due to genetic conflict in female meiosis in which centromere alleles of varying strength compete for inclusion in the ovum. According to this ‘centromere drive model’, essential centromeric proteins (like the centromeric histone, CenH3) must evolve rapidly to counteract driving centromeres, which are associated with reduced male fertility. A simpler way to allow for the rapid evolution of centromeric proteins without compromising their essential function would be via gene duplication. Duplication and specialization of centromeric proteins would allow one paralog to function as a drive suppressor in the male germline, while allowing the other to carry out its canonical centromeric role. Here, we present the finding of multipleCenH3(Cid) duplications inDrosophila.We identified four instances of Cid duplication followed by duplicate gene retention inDrosophila.TheseCidduplicates were born between 20 and 40 million years ago. This finding more than doubles the number of knownCenH3duplications in animal species and suggests that mostDrosophilaspecies encode two or moreCidparalogs, in contrast to current view that most animal species only encode a singleCenH3gene. We show that duplicate Cid genes encode proteins that have retained the ability to localize to centromeres. We present three lines of evidence, which suggest that the multiple Cid duplications have been retained due to subfunctionalization. Based on these findings, we propose the novel hypothesis that the multiple functions carried out by CenH3 proteins, i.e.,meiosis, mitosis and gametic inheritance, may be inherently incompatible with one another when encoded in a single locus.