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Review
. 2020 Aug 10;11(8):912.
doi: 10.3390/genes11080912.

Centromeres under Pressure: Evolutionary Innovation in Conflict with Conserved Function

Elisa Balzano  1 , Simona Giunta  2
Affiliations
Review

Centromeres under Pressure: Evolutionary Innovation in Conflict with Conserved Function

Elisa Balzano et al. Genes (Basel). .

Abstract

Centromeres are essential genetic elements that enable spindle microtubule attachment for chromosome segregation during mitosis and meiosis. While this function is preserved across species, centromeres display an array of dynamic features, including: (1) rapidly evolving DNA; (2) wide evolutionary diversity in size, shape and organization; (3) evidence of mutational processes to generate homogenized repetitive arrays that characterize centromeres in several species; (4) tolerance to changes in position, as in the case of neocentromeres; and (5) intrinsic fragility derived by sequence composition and secondary DNA structures. Centromere drive underlies rapid centromere DNA evolution due to the "selfish" pursuit to bias meiotic transmission and promote the propagation of stronger centromeres. Yet, the origins of other dynamic features of centromeres remain unclear. Here, we review our current understanding of centromere evolution and plasticity. We also detail the mutagenic processes proposed to shape the divergent genetic nature of centromeres. Changes to centromeres are not simply evolutionary relics, but ongoing shifts that on one side promote centromere flexibility, but on the other can undermine centromere integrity and function with potential pathological implications such as genome instability.

Keywords: HORs; centromere; centromere evolution; chromosome instability; mutagenesis; repetitive DNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CenH3 protein alignments, conservation and diversity across species. The structural elements of CenH3 proteins are illustrated, with conserved residues in blue. The histogram above the sequences shows the conserved regions: the carboxyl terminal domain and its components (L1 and α-helix) are highly preserved across eukaryotes. The shared CENP-A Targeting Domain (CATD) drives the association between proteins and centromeres [50]. Despite the variability of the amino terminal tail, this domain contains a phosphorylatable serine for CenH3 mitotic function [51]. This image is courtesy of Damien Goutte-Gattat [52].
Figure 2
Figure 2
Centromere structures in different eukaryotes. (A) The S. cerevisiae point centromere is 125 bp in size and it is composed of three centromere DNA elements (CDEs): CDEI, CDEII and CDEIII. (B) The S. pombe centromere is made of inner (ImrL and ImrR) and outer (dg and dh) inverted repetitive sequences that flank a central unique sequence (Cnt). (C) The two main satellite domains (AATAT and AAGAG) of the D. melanogaster centromere are interspersed with transposable elements (black lines). (D) A. thaliana has a 180 bp repeat unit intermingled with retrotransposons (black lines). (E) The mouse centromere is made up of major satellite sequences (MaSat) of 234 bp monomers (spanning ~6 Mb; green arrows) and minor satellite sequences (MiSat) of 120 bp monomers (spanning ~600 kb; blue arrows). (F) Human centromeres contain tandem repeats of α-satellite 171 bp monomers organized head to tail into higher order repeats (HORs). (G) The meta-polycentric centromere of P. sativum is a very long centromere of 13 families of satellite DNA repeats and one family of Ty3/gypsy retrotransposons, organized into 3–5 domains containing CenH3. (H) The polycentric or holocentric centromere of C. elegans covers the entire length of chromosome on which there are several points for microtubule attachment. In spite of this great diversity, all these centromeres perform faithful roles in chromosome segregation.
Figure 3
Figure 3
Mutagenic processes that may operate at centromere sequences and have contributed to their repetitive origins. (A) Unequal exchange following recombination can cause gain or loss of tandem repeats and DNA rearrangements. (B) Gene conversion causes the unidirectional transfer of genetic information among homologous repetitive DNA sequences and can result in reciprocal or non-reciprocal exchange (the latter is depicted). (C) Replication slippage on misalignment repeated DNA strands during replication is thought to induce centromere expansion or contraction depending on whether the hairpin (depicted)/distortion is found on the newly synthesized strand (blue repeats) or the bulge (depicted)/distortion is on the template DNA (green repeats). (D) Break-induced replication (BIR) repairs one-ended double-stranded break (DSB) substrate, produced by replication fork collapse. (E) Rolling circle replication occurs when the 3′ end circularizes, and its replication produces repeated concatemers. (F) Single strand annealing (SSA) repairs DSBs through the annealing of complementary ssDNA strands succeeded by DNA tail end digestion and ligation. These repair pathways are essential for maintaining genome stability, yet when operating on repetitive sequences (especially arranged in tandem and sharing high degree of sequence homology like at the centromere), they may result in mutagenic variability as a way for ongoing DNA evolution and shaping.
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