Adaptive Evolution of Foundation Kinetochore Proteins in Primates

Abstract

Rapid evolution is a hallmark of centromeric DNA in eukaryotic genomes. Yet, the centromere itself has a conserved functional role that is mediated by the kinetochore protein complex. To broaden our understanding about both the DNA and proteins that interact at the functional centromere, we sought to gain a detailed view of the evolutionary events that have shaped the primate kinetochore. Specifically, we performed comparative mapping and sequencing of the genomic regions encompassing the genes encoding three foundation kinetochore proteins: Centromere Proteins A, B, and C (CENP-A, CENP-B, and CENP-C). A histone H3 variant, CENP-A provides the foundation of the centromere-specific nucleosome. Comparative sequence analyses of the CENP-A gene in 14 primate species revealed encoded amino-acid residues within both the histone-fold domain and the N-terminal tail that are under strong positive selection. Similar comparative analyses of CENP-C, another foundation protein essential for centromere function, identified amino-acid residues throughout the protein under positive selection in the primate lineage, including several in the centromere localization and DNA-binding regions. Perhaps surprisingly, the gene encoding CENP-B, a kinetochore protein that binds specifically to alpha-satellite DNA, was not found to be associated with signatures of positive selection. These findings point to important and distinct evolutionary forces operating on the DNA and proteins of the primate centromere.

Absence of positive selection on CenH3 inLuzulasuggests that holokinetic chromosomes may suppress centromere drive

“…in those offering an opportunity for centromere drive (Melters et al, 2013). Similarly, adaptively evolving CenH3 has so far been detected only in lineages with asymmetric meiosis (Henikoff et al, 2001;Talbert et al, 2004Talbert et al, , 2008Hirsch et al, 2009;Schueler et al, 2010;Zedek and Bures, 2012;Finseth et al, 2015) and not in lineages displaying symmetric meiosis (Talbert et al, 2004(Talbert et al, , 2008Baker and Rogers, 2006), which is in accordance with the centromere drive model.…”

“…In fact, all the studies that have addressed selection regimes acting on CenH3 have been carried out on monocentric organisms (e.g. Henikoff et al, 2001;Talbert et al, 2004;Hirsch et al, 2009;Schueler et al, 2010) or on Caenorhabditis (Zedek and Bures, 2012) which is holokinetic in mitosis but forms a cup-like kinetochore in meiosis with ambiguous utilization of CenH3 (Chan et al, 2004;Monen et al, 2005). If the recurrent adaptive evolution of CenH3 is really a consequence of centromere drive, it should be missing (or at least less frequent) not only in lineages with symmetric meiosis but also in lineages with asymmetric meiosis that possess holokinetic chromosomes, such as the plant genus Luzula (Heckmann et al, 2013).…”

Epigenetic Inheritance of Centromeres

“…Yet centromeric DNA satellites are among the most rapidly evolving sequences in a genome. We were led to a possible resolution of this paradox with the discovery that CenH3s in Drosophila are evolving under positive selection , and this finding was subsequently extended to CENP-C, a large centromere-specific DNA-binding protein and to other eukaryotes with rapidly evolving centromeres (Malik and Henikoff 2009;Schueler et al 2010). Recurrent positive selection implies genetic conflict, and there is one situation, female meiosis, in which centromeres would be expected to compete against one another.…”

Centromere location in Arabidopsis is unaltered by extreme divergence in CENH3 protein sequence

“…Unlike canonical histones, the CENH3 protein sequence is hypervariable. In several plant and animal species, signatures of long-term adaptive evolution have been detected, especially in its N-terminal tail domain Talbert et al 2002;Schueler et al 2010). This concept is also central to the "centromere drive" hypothesis, which reasons that centromeric DNA is evolving selfishly to hijack female meiosis.…”