Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Why Do Centromeres Evolve So Fast: BIR Replication, Hypermutation, Transposition, and Molecular-Drive

Version 1 : Received: 24 December 2020 / Approved: 25 December 2020 / Online: 25 December 2020 (15:07:06 CET)

How to cite: Rice, W. Why Do Centromeres Evolve So Fast: BIR Replication, Hypermutation, Transposition, and Molecular-Drive. Preprints 2020, 2020120669 (doi: 10.20944/preprints202012.0669.v1). Rice, W. Why Do Centromeres Evolve So Fast: BIR Replication, Hypermutation, Transposition, and Molecular-Drive. Preprints 2020, 2020120669 (doi: 10.20944/preprints202012.0669.v1).

Abstract

Centromeres are among the fastest evolving genomic regions in a diverse array of organisms. The evolutionary process driving this rapid evolution has not been unambiguously established. Here I integrate diverse information to motivate a model in which centromeres evolve rapidly because of their intrinsic molecular phenotype: they tightly bind centromeric proteins throughout the cell cycle. DNA-bound proteins have been shown to cause stalling and collapse of DNA replication forks in many genomic regions, including centromeres. Collapsed replication forks generate one-sided double strand breaks (DSBs) that are repaired by the Break-Induced Repair (BIR) pathway. Here I show why this repair is expected to generate tandem repeat structure and three key features at centromeres: i) increased nucleotide substitution mutation rates, ii) out-of- register re-initiation of replication that leads to indels spanning one or more repeat units, and iii) elevated rates of large and small transpositions within centromeres and between genomic regions. These phenotypes lead to: i) a rapid rate of nucleotide substitutions within a clade of centromeric sequences, ii) continual turnover of monomers within centromeres that fosters molecular-drift and molecular-drive, and iii) recurrent quantum leaps in centromere sequence due to the formation of mosaic monomers and new sequences transposed into non-homologous centromeres. These features are plausibly the major reason centromeres evolve so rapidly. I also speculate on how the DNA sequence of centromeres might perpetually coevolve with the protein sequence of histone CENH3 –the major epigenetic mark of centromeres.

Subject Areas

Centromeres, Evolution; Break-Induce Repair; Transposition; Tandem repeat array

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