Evolutionary Turnover of Kinetochore Proteins: A Ship of Theseus?

Abstract

The kinetochore is a multiprotein complex that mediates the attachment of a eukaryotic chromosome to the mitotic spindle. The protein composition of kinetochores is similar across species as divergent as yeast and human. However, recent findings have revealed an unexpected degree of compositional diversity in kinetochores. For example, kinetochore proteins that are essential in some species have been lost in others, whereas new kinetochore proteins have emerged in other lineages. Even in lineages with similar kinetochore composition, individual kinetochore proteins have functionally diverged to acquire either essential or redundant roles. Thus, despite functional conservation, the repertoire of kinetochore proteins has undergone recurrent evolutionary turnover.

Keywords: CENP-B; CENP-T; CenH3; evolutionary dynamics; functional conservation; kinetochore.

Figure I. Dramatic variation in kinetochore architectures

We highlight three types of kinetochore arrangements to illustrate their range, from the simplest ‘point’ monocentromere in budding yeast (A), to regional monocentromeres (B), and to holocentromeres seen in many lineages including nematodes C).

Figure 1. Key Figure: Variation in kinetochore composition in four eukaryotic taxa

Kinetochores have been best-dissected biochemically in vertebrates (A) and budding yeast (B). These two kinetochores are remarkably similar in composition, with the most notable difference being the absence of CENP-M in yeast (grayed out) and the fungal-specific origin of the Dam1 complex, the functional counterpart of the Ska1 complex. However, the kinetochores in D. melanogaster (C) and holocentric Bombyx mori (D) are quite distinct from those in vertebrate and budding yeast. The conclusions that certain CCAN components are missing in both (C) and (D) are tempered by the possibility that rapid evolution might have impaired homology searches; these conclusions await further confirmation via proteomic or other experimental means.

Figure 2. Recurrent domestication of pogo-like transposases to give rise to CENP-B DNA-binding proteins

CENP-B proteins have been domesticated multiple independent times in animals and fungi. Three domesticated CENP-B-like proteins were found in fission yeast (highlighted in blue). Blue asterisks indicate potential domestications of additional CENP-B-like proteins in insects (often multiple instances per genome) predicted from bioinformatics analyses [52] that have yet to be confirmed experimentally.