Birth, evolution, and transmission of satellite-free mammalian centromeric domains

Abstract

Mammalian centromeres are associated with highly repetitive DNA (satellite DNA), which has so far hindered molecular analysis of this chromatin domain. Centromeres are epigenetically specified, and binding of the CENPA protein is their main determinant. In previous work, we described the first example of a natural satellite-free centromere on Chromosome 11. Here, we investigated the satellite-free centromeres of by using ChIP-seq with anti-CENPA antibodies. We identified an extraordinarily high number of centromeres lacking satellite DNA (16 of 31). All of them lay in LINE- and AT-rich regions. A subset of these centromeres is associated with DNA amplification. The location of CENPA binding domains can vary in different individuals, giving rise to epialleles. The analysis of epiallele transmission in hybrids (three mules and one hinny) showed that centromeric domains are inherited as Mendelian traits, but their position can slide in one generation. Conversely, centromere location is stable during mitotic propagation of cultured cells. Our results demonstrate that the presence of more than half of centromeres void of satellite DNA is compatible with genome stability and species survival. The presence of amplified DNA at some centromeres suggests that these arrays may represent an intermediate stage toward satellite DNA formation during evolution. The fact that CENPA binding domains can move within relatively restricted regions (a few hundred kilobases) suggests that the centromeric function is physically limited by epigenetic boundaries.

Reorganization of the Y Chromosomes Enhances Divergence in Israeli Mole Rats Nannospalax ehrenbergi (Spalacidae, Rodentia): Comparative Analysis of Meiotic and Mitotic Chromosomes

“…The centromere could change its position together with C-heterochromatin. We believe that centromeric transposition is a possible mechanism, because the similar data were reported for other species [ 82 , 83 ].…”

The Impact of Centromeres on Spatial Genome Architecture

“…For instance, while most centromeres from the chicken macrochromosomes comprise chromosome-specific homogeneous arrays of tandem repeats, chromosomes 5, 27, and Z comprise unique sequences. Comparative genomic studies show that the latter are likely to represent evolutionarily more recent and 'immature' centromeres that could represent an intermediate state [25]. Consistent with this, neocentromeres often form on sequences devoid of repetitive DNA [25] and tandem repeats have only recently been accumulating in some evolutionarily new centromeres.…”

“…Comparative genomic studies show that the latter are likely to represent evolutionarily more recent and 'immature' centromeres that could represent an intermediate state [25]. Consistent with this, neocentromeres often form on sequences devoid of repetitive DNA [25] and tandem repeats have only recently been accumulating in some evolutionarily new centromeres. Regardless of their evolutionary framework, the nonrepetitive nature of these centromeres provides a unique opportunity allowing their unambiguous assembly.…”

Centromere deletion in Cryptococcus deuterogattii leads to neocentromere formation and chromosome fusions

“…In addition, several studies have described neocentromere formation after deletion of native centromeres by molecular genetic engineering in fungi, chickens, and Drosophila (Alkan et al, 2007;Ishii et al, 2008;Ketel et al, 2009;Shang et al, 2013). In some organisms, the formation of neocentromeres can be deleterious, leading to disease, cancer, or infertility (Burrack and Berman, 2012;Garsed et al, 2014;Nergadze et al, 2018;Scott and Sullivan, 2013;Warburton, 2004). For example, human neocentromeres are often identified in liposarcomas (Garsed et al, 2014).…”