Centromeres under Pressure: Evolutionary Innovation in Conflict with Conserved Function

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.

Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes

“…The epigenetic foundation of centromeres is further highlighted by the existence of neo-centromeres, which are ectopic centromeres devoid of repetitive DNA that is usually found in centromeres. In humans neo-centromeres are fully functional, enabling cell division upon disruption of the endogenous centromere through ectopic CENP-A deposition [ 23 ]. However, neo-centromeres in humans appear to be generally detrimental and are associated with at least two types of cancer, suggesting they are biologically important beyond the level of an individual, such as for karyotype evolution and speciation [ 24 ].…”

Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease

“…Centromeres are characterised by repetitive DNA sequences [125,126] and retroelements [127][128][129][130]. However, it seems that specific DNA sequences are neither necessary nor sufficient for centromere specification.…”

Characterization of Chromosomal Instability in Glioblastoma

“…Growing evidence shows that CFS instability can vary between different cell types in response to replicative stress conditions, partly due to tissue-specific expression of genes located within each CFS (Debatisse et al, 2012). Similarly, transcription of non-coding RNAs can also trigger chromosomal fragility within CFSs as has been shown for other fragile regions of the genome such as centromeres (Balzano et al, 2021;Balzano and Giunta, 2020;Giunta, 2018), leading to rearrangements and aneuploidy (Giunta et al, 2021;Giunta and Funabiki, 2017). Indeed, many of the common fragile sites recorded in lymphocytes harbor genes longer than 650 kb, called very long genes (VLGs) (Smith et al, 2006;Bosco et al, 2010) and long-non-coding RNAs (lncRNAs) as we recently characterized in fibroblasts (Maccaroni et al, 2020).…”