Evolutionary New Centromeres Research Articles

Spatial inter-centromeric interactions facilitated the emergence of evolutionary new centromeres.

Centromeres of Candida albicans form on unique and different DNA sequences but a closely related species, Candida tropicalis, possesses homogenized inverted repeat (HIR)-associated centromeres. To investigate the mechanism of centromere type transition, we improved the fragmented genome assembly and constructed a chromosome-level genome assembly of C. tropicalis by employing PacBio sequencing, chromosome conformation capture sequencing (3C-seq), chromoblot, and genetic analysis of engineered aneuploid strains. Further, we analyzed the 3D genome organization using 3C-seq data, which revealed spatial proximity among the centromeres as well as telomeres of seven chromosomes in C. tropicalis. Intriguingly, we observed evidence of inter-centromeric translocations in the common ancestor of C. albicans and C. tropicalis. Identification of putative centromeres in closely related Candida sojae, Candida viswanathii and Candida parapsilosis indicates loss of ancestral HIR-associated centromeres and establishment of evolutionary new centromeres (ENCs) in C. albicans. We propose that spatial proximity of the homologous centromere DNA sequences facilitated karyotype rearrangements and centromere type transitions in human pathogenic yeasts of the CUG-Ser1 clade.

Genome Evolution in Arabideae Was Marked by Frequent Centromere Repositioning.

Centromere position may change despite conserved chromosomal collinearity. Centromere repositioning and evolutionary new centromeres (ENCs) were frequently encountered during vertebrate genome evolution but only rarely observed in plants. The largest crucifer tribe, Arabideae (∼550 species; Brassicaceae, the mustard family), diversified into several well-defined subclades in the virtual absence of chromosome number variation. Bacterial artificial chromosome-based comparative chromosome painting uncovered a constancy of genome structures among 10 analyzed genomes representing seven Arabideae subclades classified as four genera: Arabis, Aubrieta, Draba, and Pseudoturritis Interestingly, the intra-tribal diversification was marked by a high frequency of ENCs on five of the eight homoeologous chromosomes in the crown-group genera, but not in the most ancestral Pseudoturritis genome. From the 32 documented ENCs, at least 26 originated independently, including 4 ENCs recurrently formed at the same position in not closely related species. While chromosomal localization of ENCs does not reflect the phylogenetic position of the Arabideae subclades, centromere seeding was usually confined to long chromosome arms, transforming acrocentric chromosomes to (sub)metacentric chromosomes. Centromere repositioning is proposed as the key mechanism differentiating overall conserved homoeologous chromosomes across the crown-group Arabideae subclades. The evolutionary significance of centromere repositioning is discussed in the context of possible adaptive effects on recombination and epigenetic regulation of gene expression.

Epigenetic origin of evolutionary novel centromeres

Most evolutionary new centromeres (ENC) are composed of large arrays of satellite DNA and surrounded by segmental duplications. However, the hypothesis is that ENCs are seeded in an anonymous sequence and only over time have acquired the complexity of “normal” centromeres. Up to now evidence to test this hypothesis was lacking. We recently discovered that the well-known polymorphism of orangutan chromosome 12 was due to the presence of an ENC. We sequenced the genome of an orangutan homozygous for the ENC, and we focused our analysis on the comparison of the ENC domain with respect to its wild type counterpart. No significant variations were found. This finding is the first clear evidence that ENC seedings are epigenetic in nature. The compaction of the ENC domain was found significantly higher than the corresponding WT region and, interestingly, the expression of the only gene embedded in the region was significantly repressed.

Centromere repositioning explains fundamental number variability in the New World monkey genus Saimiri

Cytogenetics has historically played a key role in research on squirrel monkey (genus Saimiri) evolutionary biology. Squirrel monkeys have a diploid number of 2n=44, but vary in fundamental number (FN). Apparently, differences in FN have phylogenetic implications and are correlated with geographic regions. A number of hypothetical mechanisms were proposed to explain difference in FN: translocations, heterochromatin, or, most commonly, pericentric inversions. Recently, an additional mechanism, centromere repositioning, was discovered, which can alter chromosome morphology and FN. Here, we used chromosome banding, chromosome painting, and BAC-FISH to test these hypotheses. We demonstrate that centromere repositioning on chromosomes 5 and 15 is the mechanism that accounts for differences in FN. Current phylogenomic trees of platyrrhines provide a temporal framework for evolutionary new centromeres (ENC) in Saimiri. The X-chromosome ENC could be up to 15 million years (my) old that on chromosome 5 as recent as 0.3my. The chromosome 15 ENC is intermediate, as young as 2.24my. All ENC have abundant satellite DNAs indicating that the maturation process was fairly rapid. Callithrix jacchus was used as an outgroup for the BAC-FISH data analysis. Comparison with scaffolds from the S. boliviensis genome revealed an error in the last marmoset genome release. Future research including at the sequence level will provide better understanding of chromosome evolution in Saimiri and other platyrrhines. Probably other cases of differences in chromosome morphology and FN, both within and between taxa, will be shown to be due to centromere repositioning and not pericentric inversions.

Centromere repositioning in mammals

The evolutionary history of chromosomes can be tracked by the comparative hybridization of large panels of bacterial artificial chromosome clones. This approach has disclosed an unprecedented phenomenon: 'centromere repositioning', that is, the movement of the centromere along the chromosome without marker order variation. The occurrence of evolutionary new centromeres (ENCs) is relatively frequent. In macaque, for instance, 9 out of 20 autosomal centromeres are evolutionarily new; in donkey at least 5 such neocentromeres originated after divergence from the zebra, in less than 1 million years. Recently, orangutan chromosome 9, considered to be heterozygous for a complex rearrangement, was discovered to be an ENC. In humans, in addition to neocentromeres that arise in acentric fragments and result in clinical phenotypes, 8 centromere-repositioning events have been reported. These 'real-time' repositioned centromere-seeding events provide clues to ENC birth and progression. In the present paper, we provide a review of the centromere repositioning. We add new data on the population genetics of the ENC of the orangutan, and describe for the first time an ENC on the X chromosome of squirrel monkeys. Next-generation sequencing technologies have started an unprecedented, flourishing period of rapid whole-genome sequencing. In this context, it is worth noting that these technologies, uncoupled from cytogenetics, would miss all the biological data on evolutionary centromere repositioning. Therefore, we can anticipate that classical and molecular cytogenetics will continue to have a crucial role in the identification of centromere movements. Indeed, all ENCs and human neocentromeres were found following classical and molecular cytogenetic investigations.

Uncoupling of Satellite DNA and Centromeric Function in the Genus Equus

In a previous study, we showed that centromere repositioning, that is the shift along the chromosome of the centromeric function without DNA sequence rearrangement, has occurred frequently during the evolution of the genus Equus. In this work, the analysis of the chromosomal distribution of satellite tandem repeats in Equus caballus, E. asinus, E. grevyi, and E. burchelli highlighted two atypical features: 1) several centromeres, including the previously described evolutionary new centromeres (ENCs), seem to be devoid of satellite DNA, and 2) satellite repeats are often present at non-centromeric termini, probably corresponding to relics of ancestral now inactive centromeres. Immuno-FISH experiments using satellite DNA and antibodies against the kinetochore protein CENP-A demonstrated that satellite-less primary constrictions are actually endowed with centromeric function. The phylogenetic reconstruction of centromere repositioning events demonstrates that the acquisition of satellite DNA occurs after the formation of the centromere during evolution and that centromeres can function over millions of years and many generations without detectable satellite DNA. The rapidly evolving Equus species gave us the opportunity to identify different intermediate steps along the full maturation of ENCs.

Evolutionary-new centromeres preferentially emerge within gene deserts

A study identifying genomic restructuring and the absence of genes as conditions permissive for the seeding of new centromeres in primates

Evolutionary Formation of New Centromeres in Macaque

A systematic fluorescence in situ hybridization comparison of macaque and human synteny organization disclosed five additional macaque evolutionary new centromeres (ENCs) for a total of nine ENCs. To understand the dynamics of ENC formation and progression, we compared the ENC of macaque chromosome 4 with the human orthologous region, at 6q24.3, that conserves the ancestral genomic organization. A 250-kilobase segment was extensively duplicated around the macaque centromere. These duplications were strictly intrachromosomal. Our results suggest that novel centromeres may trigger only local duplication activity and that the absence of genes in the seeding region may have been important in ENC maintenance and progression.