Trivedi, M.; Gianfrate, F.; de Gennaro, L.; Ayllon, M.; Munson, K. M.; Hoekzema, K.; Yoo, D.; Ehmke, E.; Yoder, A. D.; Chang, S.; Lalgudi, C.; Krasnow, M. A.; Ventura, M.; Eichler, E. E.

Centromeres represent essential chromosomal structures required for faithful chromosome segregation during cell division but are paradoxically hypermutable, leading to centromere drive and reproductive isolation in closely related species. Using long-read sequencing, we generate nearly complete genomes (2.1-2.5 Gbp) from eight lemur species and characterize the sequence, epigenetic and cytogenetic structure of 223 strepsirrhini centromeres providing an alternative primate perspective of centromere evolution. No lemur centromere consists of -satellite DNA that typifies the haplorhine lineage; instead, each species evolved its own distinct higher-order centromeric repeat sequence, varying substantially in both monomer length (ranging from 41-548 bp) and primary sequence composition (GC percentages 28.7-67.9%) including centromere cooption of telomeric repeats in brown lemurs. Most centromeres show characteristic hypomethylation dip regions (110-300 kbp) as candidates for kinetochore attachment. The centromere sequence motif shows no apparent sequence homology among lemur genera, even for species separated by less than 15 million years (Lemur and Eulemur). We estimate a >6-fold increased rate in primary centromeric motif turnover in strepsirrhines when compared to haplorhines and this occurred in conjunction with positive selection of the CENP-B protein in lemur lineages. We propose that lemur radiation and centromere diversification are linked, whereby accelerated motif turnover provides a stasipatric barrier contributing to rapid chromosomal evolution.