The companion paper (Rice 2020) found that the centromeric repeats of the Western European house mouse (Mus musculus domesticus) have unusual structure: i) despite moderate pairwise sequence divergence (average = 5.9%), no monomer sequence was common and many hundreds of monomer sequences were observed, ii) local sequence divergence among neighboring monomers was nearly as high as genome-wide divergence, and iii) matching sequences were rare between side-by-side monomers. Here I integrate information from many published studies to formulate a hypothesis for the evolution of this structure. Non-matching sequences of neighboring centromeric monomers is hypothesized to be selectively favored in the context of molecular drive because it reduces the rate of monomer deletion during repair of double strand breaks (DSBs) via the Single Strand Annealing (SSA) pathway. The foundation for the hypothesis is the observation that centromeres of most populations of M. m. domestics reside close to the telomere, i.e., all their chromosomes are telocentrics. This proximity influences repair of centromeric DSBs because it places at least part of the centromere within the Telomere-Affected Repair Region (TARR; a location with increased concentrations of the shelterin-complex proteins that bind telomeres, especially TRF2). Shelterin proteins increase the level of 5’→3’ end resection at DSBs and thereby: i) decrease the frequency of repair via the c- NHEJ pathway, and ii) increase the frequency of homology-directed repair (HD-repair) –including the SSA repair pathway. It is hypothesized that certain ‘trigger’ events (e.g., sub-telomeric deletions) occur in local populations that increase the influence of TARR on the centromere. This increase elevates the occurrence of SSA repair of centromeric DSBs to a level that causes centromeres to begin to gradually shrink. Chronic shrinkage leads to coevolution between centromere size and karyotype number. Once centromeres shrink to a size below a critical minimum (that causes substantially reduced kinetochore size), fusions between non- homologous telocentrics with undersized centromeres produces metacentrics with an expanded centromere size (and a corresponding ‘quantum-jump’ in kinetochore size). These metacentrics: i) accumulate to fixation because they are favored by centromere drive, and ii) are released from the influence of TARR and thereby gradually recover larger centromere size. Fission of metacentrics with enlarged centromeres can next plausibly regenerate pairs of telocentrics with sufficiently large centromeres (which recruit normal-sized kinetochores) to be favored by centromere drive and accumulate to fixation. This fixation completes a cycle of coevolution within genomes that oscillate between two extremes: i) high karyotype number (2N = 40; all telocentrics) with larger centromeres, and ii) low karyotype number (2N << 40; mainly metacentrics) with initially small centromeres that gradually increase in size.

The pine pitch canker pathogen, Fusarium circinatum, is globally regarded as one of the most important threads to commercial pine-based forestry. Although genome sequences of this fungus are available, these remain highly fragmented or structurally ill-defined. Our overall goal was to provide high-quality assemblies for two notable strains of F. circinatum, and to characterize these in terms of coding content, repetitiveness, and the position of telomeres and centromeres. For this purpose, we used Oxford Nanopore Technologies MinION long read sequences, as well as Illumina short sequence reads. By leveraging the genomic synteny inherent to F. circinatum and its close relatives, these sequence reads were assembled to chromosome-level, where contiguous sequences mostly spanned from telomere to telomere. Comparative analyses unveiled remarkable variability in the twelfth and smallest chromosome, which is known to be dispensable. It presented a striking length polymorphism, with one strain lacking substantial portions from the chromosome's distal and proximal regions. These regions, characterized by a lower gene density and G+C content and an increased prevalence of repetitive elements, contrast starkly with the syntenic segments of the chromosome, as well as with the core chromosomes. We propose that these unusual regions might have arisen or expanded due to the presence of transposable elements. Comparison of overall chromosome structure revealed that centromeric elements often underpin intrachromosomal differences between F. circinatum strains, especially at chromosomal breakpoints. This suggested a potential role for centromeres in shaping the chromosomal architecture of F. circinatum and its relatives. The publicly available genome data generated here, together with the detailed metadata provided, represent essential resources for future studies of this important plant pathogen.

Centromeres, the chromosomal loci where spindle fibers attach during cell division to segregate chromosomes, are typically found within satellite arrays in plants and animals. Satellite arrays have been difficult to analyze because they comprise megabases of tandem head-to-tail highly repeated DNA sequences. Much evidence suggests that centromeres are epigenetically defined by the location of nucleosomes containing the centromere-specific histone H3 variant cenH3, independently of the DNA sequences where they are located; however, the reason that cenH3 nucleosomes are generally found on rapidly evolving satellite arrays has remained unclear. Recently, long read sequencing technology has clarified the structures of satellite arrays and sparked rethinking of how they evolve, while new experiments and analyses have helped bring both understanding and further speculation about the role these highly repeated sequences play in centromere identification.

The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.