Cellular and Molecular Mechanisms of Centromere Drive

Abstract

The asymmetric outcome of female meiosis I, whereby an entire set of chromosomes are discarded into a polar body, presents an opportunity for selfish genetic elements to cheat the process and disproportionately segregate to the egg. Centromeres, the chromosomal loci that connect to spindle microtubules, could potentially act as selfish elements and “drive” in meiosis. We review the current understanding of the genetic and epigenetic contributions to centromere identity and describe recent progress in a powerful model system to study centromere drive in mice. The progress includes mechanistic findings regarding two main requirements for a centromere to exploit the asymmetric outcome of female meiosis. The first is an asymmetry between centromeres of homologous chromosomes, and we found this is accomplished through massive changes in the abundance of the repetitive DNA underlying centromeric chromatin. The second requirement is an asymmetry in the meiotic spindle, which is achieved through signaling from the oocyte cortex that leads to asymmetry in a posttranslational modification of tubulin, tyrosination. Together, these two asymmetries culminate in the biased segregation of expanded centromeres to the egg, and we describe a mechanistic framework to understand this process.

Human chromosome‐specific aneuploidy is influenced by DNA ‐dependent centromeric features

“…Certainly, it is known that mammalian oogenesis meiosis is naturally biased, because homologous chromosomes have unequal chances of being inherited by the offspring (Henikoff & Malik, ). In these conditions of female asymmetric meiosis, “stronger” centromeres are known to preferentially segregate to the egg due to higher amounts of centromere proteins (Lampson & Black, ). This could explain the positive evolution of the centromere toward the presence of a higher number of CENP‐B boxes and the absence of CENP‐B boxes at the Y chromosome which does not undergo this female‐specific selection.…”

“…A direct correlation between centromere size and bias in chromosome segregation was demonstrated in mouse asymmetric female meiosis, a phenomenon defined as centromere drive (Henikoff & Malik, ). Here it was shown that, between two homologous chromosomes, the chromosome that carries a centromere with a higher amount of centromeric DNA sequences and centromere proteins (a concept globally defined as “centromere strength”) was preferentially retained in the egg during the first meiotic division (Chmátal et al , ; Iwata‐Otsubo et al , ; Lampson & Black, ). This could explain part of the molecular mechanisms behind asymmetric division in female gametogenesis.…”

Sex chromosome quadrivalents in oocytes of the African pygmy mouse Mus minutoides that harbors non-conventional sex chromosomes

“…First, the proportion of quadrivalents with fewer than three crossovers might be overestimated because of the formation of MLH1independent crossovers, which are estimated to account for about 10% of all crossovers in M. musculus (Baker et al 1996;Woods et al 1999;Marcon and Moens 2003;Kolas et al 2005b;Guillon et al 2005). Moreover, the segregation of specific chromosome pairs or of an achiasmate univalent chromosome might deviate from random in mouse oocytes (LeMaire-Adkins and Hunt 2000; Lampson and Black 2017;Wu et al 2018). One might also speculate on a mechanism promoting the segregation of achiasmate X* and Y chromosomes, somehow similar to the mechanism ensuring the male meiosis I segregation of achiasmate X and Y chromosomes in closely related species from the subgenus Nannomys (Jotterand-Bellomo 1981;Britton-Davidian et al 2012).…”

Functional Significance of Satellite DNAs: Insights From Drosophila

“…"Strong" centromeres contain more satellite repeats; they form more CENP-A nucleosomes for kinetochore assembly and bind more kinetochore proteins (CENP-C and HEC1) relative to the "weaker" centromeres (Iwata-Otsubo et al, 2017). This asymmetry of the meiotic spindle of division is established owing to the presence of CDC42 signaling and RAN-GTPase gradient, which cause the cortical polarization and subsequent migration of one spindle to the cortex in the site of the formation of the polar body, and to post-translational modification (tyrosination) of microtubule α-tubulin (Akera et al, 2017;Lampson and Black, 2017;Kursel and Malik, 2018). The second spindle of division remains in the center of the cell and does not undergo the modification.…”