Islands of retroelements are the major components ofDrosophilacentromeres

Abstract

Centromeres are essential chromosomal regions that mediate kinetochore assembly and spindle attachments during cell division. Despite their functional conservation, centromeres are amongst the most rapidly evolving genomic regions and can shape karyotype evolution and speciation across taxa. Although significant progress has been made in identifying centromere-associated proteins, the highly repetitive centromeres of metazoans have been refractory to DNA sequencing and assembly, leaving large gaps in our understanding of their functional organization and evolution. Here, we identify the sequence composition and organization of the centromeres of Drosophila melanogaster by combining long-read sequencing, chromatin immunoprecipitation for the centromeric histone CENP-A, and high-resolution chromatin fiber imaging. Contrary to previous models that heralded satellite repeats as the major functional components, we demonstrate that functional centromeres form on islands of complex DNA sequences enriched in retroelements that are flanked by large arrays of satellite repeats. Each centromere displays distinct size and arrangement of its DNA elements but is similar in composition overall. We discover that a specific retroelement, G2/Jockey-3, is the most highly enriched sequence in CENP-A chromatin and is the only element shared among all centromeres. G2/Jockey-3 is also associated with CENP-A in the sister species Drosophila simulans, revealing an unexpected conservation despite the reported turnover of centromeric satellite DNA. Our work reveals the DNA sequence identity of the active centromeres of a premier model organism and implicates retroelements as conserved features of centromeric DNA.

The Impact of Centromeres on Spatial Genome Architecture

“…Still, in some plant organisms, including Oryza sativa and Arabidopsis thaliana, the molecular structure of large centromeric regions for several chromosomes has been determined ( Figure 1 and Box 1) [14][15][16][17][18]. In addition, a recent study characterized the organization and sequence composition of all native Drosophila centromeres, confirming the structure unraveled by original mapping efforts on the Dp1230 minichromosome ( Figure 1 and Box 1) [19,20]. Finally, the complete sequence of the first human centromere has also been released by assembling the higher-order-repeat (HOR) structure of the human chromosome Y satellite array ( Figure 1 and Box 1) [21].…”

Early Diverging Fungus Mucor circinelloides Lacks Centromeric Histone CENP-A and Displays a Mosaic of Point and Regional Centromeres

“…The pericentric regions of M. circinelloides are large ($15-75 kb), gene free, and transcriptionally silenced sequences that are interspersed by Grem-LINE1s, which are repeats of a LINE1-like non-LTR retrotransposable element. Several retroelements have been identified in the centromeres and neocentromeres of highly diverged eukaryotes: non-LTR LINE1-like elements in mammals [43][44][45][46][47][48] and Jockey elements in the fruit fly [49] and LTR retrotransposons in plants [50] and fungi [23,38]. Based on these findings, a model has been proposed that CENP-A is recruited by genomic sequences rich in repeats and transposable elements and thus gives rise to the centromeres [51].…”

Early diverging fungus Mucor circinelloides lacks centromeric histone CENP-A and displays a mosaic of point and regional centromeres

“…The pericentric regions of M. circinelloides are large (∼15-75 kb), gene-free, and transcriptionally silenced sequences that are interspersed by Grem-LINE1s, which are repeats of a LINE1-like non-LTR retrotransposable element. These types of retroelements have been identified in the centromeres and neocentromeres of highly diverged eukaryotes, especially LINE1-like elements in mammals 36–41 and also other non-LTR retroelements as active components of fruit fly centromeres 42 , and LTR retrotransposons in plants 43 and fungi 22 . Based on these findings, a model has been proposed that CENP-A is recruited by genomic sequences rich in retrotransposable elements and thus, gives rise to the centromeres 44 .…”