Adaptive Evolution of Centromeric Proteins

Abstract

Kinetochore proteins assemble at centromeres and mediate chromosome segregation during eukaryotic cell division. This conserved function conceals a paradox; essential inner kinetochore proteins, CenH3 and CENP‐C, evolve rapidly under positive selection in primates, plants and insects. This paradox may be explained by a genetic conflict between selfish DNA sequences at the centromere and the kinetochore proteins that bind them. The centromere drive hypothesis provides a framework for understanding this conflict and makes predictions for patterns of evolution in the composition of the kinetochore. In contrast with the rapidly evolving inner kinetochore, the components of the outer kinetochore do not make contacts with centromeric DNA and evolve more slowly. Furthermore, genetic conflict at the centromere may underlie observed taxonomic differences in the rate of evolution of kinetochore proteins among species with different meiotic programs.

Key Concepts:

  • Despite an essential and conserved function, some centromere‐binding proteins evolve rapidly.

  • In contrast to canonical histone H3, the centromeric variant of histone H3 displays striking patterns of positive selection in functionally critical domains.

  • CENP‐C displays rapid evolution across a diverse taxa; the functional consequences of this rapid evolution have not yet been studied.

  • Asymmetric female meiosis provides an opportunity for competition among centromeres for evolutionary success but has deleterious consequences in male meiosis leading to genetic conflict.

  • Genetic conflict between centromeres and centromere‐binding proteins can explain the divergent patterns of evolution between inner and outer kinetochore proteins, as well as taxonomic differences in rapid evolution of centromeric proteins.

Keywords: centromeres; chromatin; rapid evolution; gene duplication; outer kinetochore; fibrous corona; microtubules; female meiosis; mitosis

Figure 1.

Kinetochore formation and structure (Cheeseman and Desai, ). (a) After DNA replication and cell division the Mis18 complex prepares centromeric chromatin for additional CenH3 deposition. It is unknown whether a chaperone is universally required for proper CenH3 loading, but many species encode CenH3 chaperones (Scm3/HJURP) that are essential for CenH3 deposition. (b) The CCAN proteins form the structure of the inner kinetochore, directly binding both centromeric DNA and nucleosomes containing CenH3. The CCAN forms the attachment site for the proteins of outer kinetochore and fibrous corona, acting as a link between the centromeric DNA and the rest of the kinetochore. (c) The outer kinetochore and fibrous corona binds the CCAN at the beginning of mitosis. Proteins of the fibrous corona regulate the spindle checkpoint and ensure proper microtubule binding before dissociating from the kinetochore. The complexes of the outer kinetochore remain throughout mitosis and provide mechanism for microtubules to transmit force to the chromosome.

Figure 2.

Centromeric histones differ from canonical histone H3 in sequence and function. (a) Canonical histones are highly conserved, whereas CenH3 are highly divergenced. The variation of the N‐terminal tail of CenH3 is so great that it is not possible to align these features across taxa. (b) Loop 1 domains within the histone fold domain also vary in sequence and length in CenH3s but not canonical H3 proteins. (c) A crystal structure of the histone fold domains of the CenH3 (blue)/ H4 (yellow) heterotetramer (Sekulic et al., ). The amino acids of the rapidly evolving, centromere‐targeting loop 1 are highlighted in red.

Figure 3.

CENP‐C proteins show little homology across taxa. (a) CENP‐C evolves so rapidly that only a 24 amino‐acids domain (referred to as the CENP‐C domain) is homologous between widely diverged species. More closely related species share larger regions of homology. The amino and C‐terminal regions are homologous throughout vertebrates, with a smaller carboxyl motif also present in fungi. Plants share only the CENP‐C motif with animals but have their own homologous region in the N‐terminus (Talbert et al., ). (b) In addition to the rapid evolution in amino acid sequence, CENP‐C is experiencing repeated exon duplication and deletion. Cereal crops have undergone duplication and subsequent deletion of exons 8 and 9. This deletion is followed by repeated duplication and loss of adjacent exons 10 and 11 (Talbert et al., ).

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Further Reading

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Roach, Kevin C, Ross, Benjamin D, and Malik, Harmit S(Nov 2011) Adaptive Evolution of Centromeric Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022868]