Molecular Dynamics and Evolution of Centromeres in the Genus Equus

Abstract

The centromere is the chromosomal locus essential for proper chromosome segregation. While the centromeric function is well conserved and epigenetically specified, centromeric DNA sequences are typically composed of satellite DNA and represent the most rapidly evolving sequences in eukaryotic genomes. The presence of satellite sequences at centromeres hampered the comprehensive molecular analysis of these enigmatic loci. The discovery of functional centromeres completely devoid of satellite repetitions and fixed in some animal and plant species represented a turning point in centromere biology, definitively proving the epigenetic nature of the centromere. The first satellite-free centromere, fixed in a vertebrate species, was discovered in the horse. Later, an extraordinary number of satellite-free neocentromeres had been discovered in other species of the genus Equus, which remains the only mammalian genus with numerous satellite-free centromeres described thus far. These neocentromeres arose recently during evolution and are caught in a stage of incomplete maturation. Their presence made the equids a unique model for investigating, at molecular level, the minimal requirements for centromere seeding and evolution. This model system provided new insights on how centromeres are established and transmitted to the progeny and on the role of satellite DNA in different aspects of centromere biology.

Keywords: CENP-A; centromere repositioning; centromere sliding; genus Equus; karyotype evolution; neocentromeres; satellite DNA.

Figure 1

Schematic representation of the chromosomal distribution of satellite DNA obtained by FISH experiments in E. caballus, E. asinus, E. grevyi and E. burchelli. (A) In E. caballus, all centromeres, with the exception of that of chromosome 11, are associated with satellite DNA sequences. Satellite DNA is also present at an interstitial position on the long arm of chromosome X. (B) In E. asinus, 18 centromeres are not associated with satellite DNA sequences at the FISH resolution level. Satellite DNA sequences are present at 13 non-centromeric chromosome ends. Satellite DNA is present at an interstitial position on the long arm of chromosome X. (C) In E. grevyi, 17 centromeres are void of satellite DNA and satellite DNA sequences are present at 15 non-centromeric termini and at an interstitial position of the long arm of the X chromosome. (D) In E. burchelli, 7 centromeres do not display satellite DNA sequences and 9 non-centromeric chromosome ends are associated with satellite DNA. Satellite DNA loci are present in the pericentromeric region of chromosomes 1, 4 and 5. Modified from [14].

Figure 2

Model for the maturation of a centromere during evolution. Different routes are delineated leading to a mature satellite-based repositioned centromere (D) from an ancestral satellite-based centromere (A) through satellite-free intermediates (B,C,E,F). Route A–D: a neocentromere arises in a satellite-free region and satellite DNA remains at the ancestral position; the ancestral satellite DNA is lost from the non-centromeric terminus and, finally, the neocentromere acquire satellite repeats, giving rise to a “mature” neocentromere. This route follows the previously proposed model [14]. Routes A, B, E, D or A, B, C, F, D: at an already functional satellite-free neocentromere, amplification occurs as an intermediate step toward complete maturation of the neocentromere. Neocentromere maturation and loss of satellite DNA from the old centromere site are independent events that can occur at different stages. The 16 donkey chromosomes carrying a satellite-free neocentromere and the horse chromosome 11 exemplify satellite-free intermediates (B,C,E,F) and are listed below each step. It cannot be excluded that sequence amplification precedes neocentromere formation (G), but no chromosome corresponding to this step was found so far. Modified from [13,14].