Adaptive evolution of the histone fold domain in centromeric histones

Abstract

Centromeric DNA, being highly repetitive, has been refractory to molecular analysis. However, centromeric structural proteins are encoded by single-copy genes, and these can be analyzed by using standard phylogenetic tools. The centromere-specific histone, CenH3, replaces histone H3 in centromeric nucleosomes, and is required for the proper distribution of chromosomes during cell division. Whereas histone H3s are nearly identical between species, CenH3s are divergent, with an N-terminal tail that is highly variable in length and sequence. Both the N-terminal tail and histone fold domain (HFD) are subject to adaptive evolution in Drosophila. Similarly, comparisons between Arabidopsis thaliana and Arabidopsis arenosa detected adaptive evolution, but only in the N-terminal tail. We have extended our evolutionary analyses of CenH3s to other members of the Brassicaceae, which allowed the detection of positive selection in both the N-terminal tail and in the HFD. We find that adaptively evolving sites in the HFD can potentially interact with DNA, including sites in the loop 1 region of the HFD that are required for centromeric targeting in Drosophila. Other adaptively evolving sites in the HFD can be localized on the structure of the nucleosome core particle, revealing an extended surface in addition to loop 1 in which conformational changes might alter histone-DNA contacts or water bridges. The identification of adaptively evolving sites provides a structural basis for the interaction between centromeric DNA and the protein that is thought to underlie the evolution of centromeres and the accumulation of pericentric heterochromatin.