What makes a centromere?

Centromeres are the eukaryotic chromosomal sites at which the kinetochore forms and attaches to spindle microtubules to orchestrate chromosomal segregation in mitosis and meiosis. Although centromeres are essential for cell division, their sequences are not conserved and evolve rapidly. Centromeres vary dramatically in size and organization. Here we categorize their diversity and explore the evolutionary forces shaping them. Nearly all centromeres favor AT-rich DNA that is gene-free and transcribed at a very low level. Repair of frequent centromere-proximal breaks probably contributes to their rapid sequence evolution. Point centromeres are only ~125 bp and are specified by common protein-binding motifs, whereas short regional centromeres are 1-5 kb, typically have unique sequences, and may have pericentromeric repeats adapted to facilitate centromere clustering. Transposon-rich centromeres are often ~100-300 kb and are favored by RNAi machinery that silences transposons, by suppression of meiotic crossovers at centromeres, and by the ability of some transposons to target centromeres. Megabase-length satellite centromeres arise in plants and animals with asymmetric female meiosis that creates centromere competition, and favors satellite monomers one or two nucleosomes in length that position and stabilize centromeric nucleosomes. Holocentromeres encompass the length of a chromosome and may differ dramatically between mitosis and meiosis. We propose a model in which low level transcription of centromeres facilitates the formation of non-B DNA that specifies centromeres and promotes loading of centromeric nucleosomes.