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Homomorphic sex chromosomes and their turnover are common in teleosts. We investigated the evolution of nascent sex chromosomes in several populations of two sister species of African annual killifishes, Nothobranchius furzeri and N. kadleci, focusing on their under-studied repetitive landscape. We combined bioinformatic analyses of the repeatome with molecular cytogenetic techniques, including comparative genomic hybridization, fluorescence in situ hybridization with satellite sequences, ribosomal RNA genes (rDNA) and bacterial artificial chromosomes (BACs), and immunostaining of SYCP3 and MLH1 proteins to mark lateral elements of synaptonemal complexes and recombination sites, respectively. Both species share the same heteromorphic XY sex chromosome system, which thus evolved prior to their divergence. This was corroborated by sequence analysis of a putative master sex determining (MSD) gene gdf6Y in both species. Based on their divergence, differentiation of the XY sex chromosome pair started approximately 2 million years ago. In all populations, the gdf6Y gene mapped within a region rich in satellite DNA on the Y chromosome long arms. Despite their heteromorphism, X and Y chromosomes mostly pair regularly in meiosis, implying synaptic adjustment. In N. kadleci, Y-linked paracentric inversions like those previously reported in N. furzeri were detected. An inversion involving the MSD gene may suppress occasional recombination in the region, which we otherwise evidenced in the N. furzeri population MZCS-121 of the Limpopo clade lacking this inversion. Y chromosome centromeric repeats were reduced compared with the X chromosome and autosomes, which points to a role of relaxed meiotic drive in shaping the Y chromosome repeat landscape. We speculate that the recombination rate between sex chromosomes was reduced due to heterochiasmy. The observed differences between the repeat accumulations on the X and Y chromosomes probably result from high repeat turnover and may not relate closely to the divergence inferred from earlier SNP analyses.

Repetitive DNA may have significant impact on genome evolution. African annual killifishes of the genusNothobranchius(Teleostei: Nothobranchiidae), which has adapted to temporary water pools in African savannahs, possess genomes with high repeat content. They are also characterized by rapid karyotype and sex chromosome evolution but the role of genome repeats in these processes remains largely unknown. Here, we analyzed the distribution of telomeric (TTAGGG)nrepeat and Nfu-SatC satellite DNA (isolated formerly fromN. furzeri) by fluorescencein situhybridization in representatives across theNothobranchiusphylogeny (15 species), and withFundulosoma thierryias an outgroup. All analyzed taxa shared the presence of Nfu-SatC repeat but with diverse organization and distribution on chromosomes (from small clusters scattered genome-wide, to large localized accumulations, or a combined pattern). Nfu-SatC landscape was similar in conspecific populations ofN. guentheriandN. melanospilusbut slightly-to-moderately differed between populations ofN. pienaari, and between closely relatedN. kuhntaeandN. orthonotus. Inter-individual variability in Nfu-SatC patterns was found inN. orthonotusandN. krysanovi, including distinct segments present often in heterozygous condition. We revealed mostly no sex-linked patterns of studied repeat’s distribution in any of the sampled species including those with known sex chromosomes. Only inN. brieni(having an X1X2Y multiple sex chromosome system), Nfu-SatC probe covered substantial portion of the Y chromosome, similarly as formerly found inN. furzeriandN. kadleci(XY sex chromosomes), sister species not closely related toN. brieni. All studied species further shared patterns of telomeric FISH, with expected signals at the ends of all chromosomes and no additional interstitial telomeric sites. In summary, we revealed i) the presence of conserved satDNA class inNothobranchiusclade (a rare pattern among ray-finned fishes), ii) independent trajectories ofNothobranchiussex chromosome diferentiation, with recurrent and convergent accumulation of Nfu-SatC on the Y chromosome in some species, and iii) genus-wide shared propensity to loss of telomeric repeats during the mechanism of interchromosomal rearrangements. Collectively, our findings advance our understanding of genome structure, mechanisms of karyotype reshuffling and sex chromosome differentiation inNothobranchiuskillifishes from the genus-wide perspective.

Satellite DNA (satDNA) is rapidly evolving class of tandem repeats with some motifs being involved in centromere organization and function. Rapid co-evolution of centromeric satDNA and associated proteins has been mostly attributed to the so-called centromere drive. To identify repeats associated with centromeric regions and test for the role of meiotic drive in their evolution, we investigated satDNA across Southern and Coastal clades of African annual killifishes of the genus Nothobranchius. C-banding showed expansion of (peri)centromeric heterochromatin regions in the Southern-clade killifishes. Molecular cytogenetic and bioinformatic analyses further revealed that two previously identified satellites, Nfu-SatA and Nfu-SatB, are associated with centromeres only in one lineage of the Southern clade. Nfu-SatB was, however, detected outside centromeres also in other members of the Coastal clade, which is consistent with the "library" hypothesis of satDNA evolution. We also identified a novel satDNA, Cl-36, associated with (peri)centromeres in N. foerschi, N. guentheri and N. rubripinnis from the Coastal clade. Our findings could be explained by centromere drive shaping karyotype change and centromeric repeat turnover in Nothobranchius species with possible reversal of spindle polarity within the Southern clade.

The karyotype differentiation of the twelve known members of the Nothobranchius ugandensis Wildekamp, 1994 species group is reviewed and the karyotype composition of seven of its species is described herein for the first time using a conventional cytogenetic protocol. Changes in the architecture of eukaryotic genomes often have a major impact on processes underlying reproductive isolation, adaptation and diversification. African annual killifishes of the genus Nothobranchius Peters, 1868 (Teleostei: Nothobranchiidae), which are adapted to an extreme environment of ephemeral wetland pools in African savannahs, feature extensive karyotype evolution in small, isolated populations and thus are suitable models for studying the interplay between karyotype change and species evolution. The present investigation reveals a highly conserved diploid chromosome number (2n = 36) but a variable number of chromosomal arms (46–64) among members of the N. ugandensis species group, implying a significant role of pericentric inversions and/or other types of centromeric shift in the karyotype evolution of the group. When superimposed onto a phylogenetic tree based on molecular analyses of two mitochondrial genes the cytogenetic characteristics did not show any correlation with the phylogenetic relationships within the lineage. While karyotypes of many other Nothobranchius spp. studied to date diversified mainly via chromosome fusions and fissions, the N. ugandensis species group maintains stable 2n and the karyotype differentiation seems to be constrained to intrachromosomal rearrangements. Possible reasons for this difference in the trajectory of karyotype differentiation are discussed. While genetic drift seems to be a major factor in the fixation of chromosome rearrangements in Nothobranchius, future studies are needed to assess the impact of predicted multiple inversions on the genome evolution and species diversification within the N. ugandensis species group.

The African weakly electric elephantfish family Mormyridae comprises 22 genera and almost 230 species. Up-to-date cytogenetic information was available for 17 species representing 14 genera. Here we report chromosome number and morphology in Hyperopisus bebe (Lacepède, 1803) and Pollimyrus isidori (Valenciennes, 1847) collected from the White Nile system in southwestern Ethiopia. Both taxa displayed the diploid chromosome number 2n = 40, but they differed in fundamental numbers: FN = 66 in H. bebe and FN = 72 in P. isidori; previously the same diploid chromosome number 2n = 40 was reported in an undescribed species of Pollimyrus Taverne, 1971 (FN = 42) from the same region. Our results demonstrate that not only pericentric inversions, but fusions also played a substantial role in the evolution of the mormyrid karyotype structure. If the hypothesis that the karyotype structure with 2n = 50–52 and prevalence of the uni-armed chromosomes close to the ancestral condition for the family Mormyridae is correct, the most derived karyotype structures are found in the Mormyrus Linnaeus, 1758 species with 2n = 50 and the highest number of bi-armed elements in their compliments compared to all other mormyrids and in Pollimyrus isidori with the highest number of bi-armed elements among the mormyrids with 2n = 40.

We studied the mitotic chromosome sets in three elephantfish species of the genus Mormyrus (Mormyridae, Osteoglossiformes) occurring in the White Nile and Omo-Turkana basins in south-western Ethiopia. The karyotype structure (2n = 50, FN = 84) appeared to be similar in M. caschive, M. hasselquistii and M. kannume. The Mormyrus is 14th mormyrid genera studied cytogenetically and its karyotype is unique within the family because of the least number of uni-armed chromosomes.

Background Prostate cancer is one of the most common and socially significant cancers among men. The aim of our study was to reveal changes in miRNA expression profiles associated with lymphatic dissemination in prostate cancer and to identify the most prominent miRNAs as potential prognostic markers for future studies. Methods High-throughput miRNA sequencing was performed for 44 prostate cancer specimens taken from Russian patients, with and without lymphatic dissemination (N1 – 20 samples; N0 – 24 samples). Results We found at least 18 microRNAs with differential expression between N0 and N1 sample groups: miR-182-5p, miR-183-5p, miR-96-5p, miR-25-3p, miR-93-5p, miR-7-5p, miR-615-3p, miR-10b, miR-1248 (N1-miRs; elevated expression in N1 cohort; p miR-1271-5p, miR-184, miR-222-3p, miR-221-5p, miR-221-3p, miR-455-3p, miR-143-5p, miR-181c-3p and miR-455-5p (N0-miRs; elevated expression in N0; p . The expression levels of N1-miRs were highly correlated between each other (the same is applied for N0-miRs) and the expression levels of N0-miRs and N1-miRs were anti-correlated. The tumor samples can be divided into two groups depending on the expression ratio between N0-miRs and N1-miRs. Conclusions We found the miRNA expression signature associated with lymphatic dissemination, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.

The elephantfish family Mormyridae is the most diverse lineage of the primitive teleostean clade Osteoglossomorpha distributed in inland waters of all continents except Antarctica and Europe. The family Mormyridae is endemic to Africa and includes 22 genera and almost 230 species. The evolutionary radiation of mormyrids most probably should be attributed to their capability of both generating and receiving weak electric signals. Up-to-date cytogenetic studies have revealed substantial karyotype differentiation among the nine investigated elephantfish species and genera (a single species studied per each genus). In the present study, karyotypes of five species representing five mormyrid genera (four unexplored ones) collected from the White Nile system in southwestern Ethiopia are described for the first time. The results show substantial variety of the diploid chromosome and fundamental numbers: 2n = 48 and FN = 54 inBrevimyrus niger(Günther, 1866), 2n = 50 and FN = 72 inCyphomyrus petherici(Boulenger, 1898), 2n = 50 and FN = 78 inHippopotamyrus pictus(Marcusen, 1864), 2n = 50 and FN = 76 inMarcusenius cyprinoides(Linnaeus, 1758), 2n = 52 and FN = 52 inMormyrops anguilloides(Linnaeus, 1758). Karyotype structure in the latter species seems to be close to the ancestral condition for the family. This hypothesis is discussed in the light of available data on karyotype diversity and phylogeny of mormyrids.

Sex chromosomes are generally derived from a pair of classical type-A chromosomes, and relatively few alternative models have been proposed up to now.(1,2) B chromosomes (Bs) are supernumerary and dispensable chromosomes with non-Mendelian inheritance found in many plant and animal species(3,4) that have often been considered as selfish genetic elements that behave as genome parasites.(5,6) The observation that in some species Bs can be either restricted or predominant in one sex(7–14) raised the interesting hypothesis that Bs could play a role in sex determination.(15) The characterization of putative B master sex-determining (MSD) genes, however, has not yet been provided to support this hypothesis. Here, in Astyanax mexicanus cavefish originating from Pachón cave, we show that Bs are strongly male predominant. Based on a high-quality genome assembly of a B-carrying male, we characterized the Pachón cavefish B sequence and found that it contains two duplicated loci of the putative MSD gene growth differentiation factor 6b (gdf6b). Supporting its role as an MSD gene, we found that the Pachón cavefish gdf6b gene is expressed specifically in differentiating male gonads, and that its knockout induces male-to-female sex reversal in B-carrying males. This demonstrates that gdf6b is necessary for triggering male sex determination in Pachón cavefish. Altogether these results bring multiple and independent lines of evidence supporting the conclusion that the Pachón cavefish B is a “B-sex” chromosome that contains duplicated copies of the gdf6b gene, which can promote male sex determination in this species.

Sex chromosomes are generally derived from a pair of classical type-A chromosomes, and relatively few alternative models have been proposed up to now. B chromosomes (Bs) are supernumerary and dispensable chromosomes with non-Mendelian inheritance found in many plant and animal species, that have often been considered as selfish genetic elements that behave as genome parasites. The observation that in some species Bs can be either restricted or predominant in one sex raised the interesting hypothesis that Bs could play a role in sex determination. The characterization of putative B master sex-determining (MSD) genes, however, has not yet been provided to support this hypothesis. Here, in Astyanax mexicanus cavefish originating from Pachon cave, we show that Bs are strongly male-predominant. Based on a high-quality genome assembly of a B-carrying male, we characterized the Pachon cavefish B sequence and found that it contains two duplicated loci of the putative MSD gene growth differentiation factor 6b gdf6b). Supporting its role as an MSD gene, we found that the Pachon cavefish gdf6b gene is expressed specifically in differentiating male gonads, and that its knockout induces male-to-female sex reversal in B-carrying males. This demonstrates that gdf6b is necessary for triggering male sex determination in Pachon cavefish. Altogether these results bring multiple and independent lines of evidence supporting the conclusion that the Pachon cavefish B is a “B-sex” chromosome containing duplicated copies of the gdf6b gene acting as an MSD gene promoting male sex determination in this species.

Background Vagal paragangliomas (VPGLs) belong to a group of rare head and neck neuroendocrine tumors. VPGLs arise from the vagus nerve and are less common than carotid paragangliomas. Both diagnostics and therapy of the tumors raise significant challenges. Besides, the genetic and molecular mechanisms behind VPGL pathogenesis are poorly understood. Methods The collection of VPGLs obtained from 8 patients of Russian population was used in the study. Exome library preparation and high-throughput sequencing of VPGLs were performed using an Illumina technology. Results Based on exome analysis, we identified pathogenic/likely pathogenic variants of the SDHx genes, frequently mutated in paragangliomas/pheochromocytomas. SDHB variants were found in three patients, whereas SDHD was mutated in two cases. Moreover, likely pathogenic missense variants were also detected in SDHAF3 and SDHAF4 genes encoding for assembly factors for the succinate dehydrogenase (SDH) complex. In a patient, we found a novel variant of the IDH2 gene that was predicted as pathogenic by a series of algorithms used (such as SIFT, PolyPhen2, FATHMM, MutationTaster, and LRT). Additionally, pathogenic/likely pathogenic variants were determined for several genes, including novel genes and some genes previously reported as associated with different types of tumors. Conclusions Results indicate a high heterogeneity among VPGLs, however, it seems that driver events in most cases are associated with mutations in the SDHx genes and SDH assembly factor-coding genes that lead to disruptions in the SDH complex.

Background Carotid and vagal paragangliomas (CPGLs and VPGLs) are rare neoplasms that arise from the paraganglia located at the bifurcation of carotid arteries and vagal trunk, respectively. Both tumors can occur jointly as multiple paragangliomas accounting for approximately 10 to 20% of all head and neck paragangliomas. However, molecular and genetic mechanisms underlying the pathogenesis of multiple paragangliomas remain elusive. Case presentation We report a case of multiple paragangliomas in a patient, manifesting as bilateral CPGL and unilateral VPGL. Tumors were revealed via computed tomography and ultrasound study and were resected in two subsequent surgeries. Both CPGLs and VPGL were subjected to immunostaining for succinate dehydrogenase (SDH) subunits and exome analysis. A likely pathogenic germline variant in the SDHD gene was indicated, while likely pathogenic somatic variants differed among the tumors. Conclusions The identified germline variant in the SDHD gene seems to be a driver in the development of multiple paragangliomas. However, different spectra of somatic variants identified in each tumor indicate individual molecular mechanisms underlying their pathogenesis.

The genes controlling meiotic progression in plants and not affecting mitotic progression are most widely studied in maize Zea mays and cruciferous plant Arabidopsis thaliana. These include the genes controlling the differentiation of somatic cells into sporogenous ones and meiosis-initiating genes, genes encoding meiosis-specific proteins of chromosomes and synaptonemal complexes, genes of mediator proteins and enzymes of meiotic DNA recombination and crossover, and genes controlling meiosis-specific behavior of centromeres and the course of two meiotic divisions. A large number of such genes have been cloned and studied at the molecular level. The studies of meiotic genes in rice Oriza sativa are actively developing, while studies of corresponding genes in barley Hordeum vulgare, rye Secale cereale, tomato Solanum lycopersicum, and hexaploid wheat Triticum aestivum are less advanced. To identify meiotic genes, chemical and insertional mutagenesis, genetic and cytological analysis, genomic and proteomic studies, methods of reverse genetics, and bioinformatics are used.

Practical aspects of the application of cytogenetic indicators during the analysis of the environmental state are considered in the article. Cytogenetic characteristics of the Nothobranchius rachovii fish species (proposed as a test object) are presented.

After completing their functioning, synaptonemal complexes (SCs) degrade during the diplotene stage. In the pollen mother cells of rye Secale cereale L., this occurs through the formation of gaps in lateral elements of the SCs and the shortening of fragments of SCs until their complete disappearance. However, when contrasting SCs with silver nitrate solution at a pH 3.5–4.5, these gaps appear to be filled with threads associated with SC lateral elements. As the diplotene stage proceeds and gradual degradation of SC fragments continues, these threads turn into submicroscopic spirals. In this study, we found that the threads and spirals associated with degrading synaptonemal complexes are stained by antibodies to the ASY1 protein of Arabidopsis thaliana lateral elements and thus are degradation products of the lateral elements of SCs.

In the present paper, we clarify the genetic structure and taxonomy of six vole species occurring in Mongolia including Microtus mongolicus, M. maximowiczii, M. limnophilus, Eolagurus luteus, E. przewalskii and Lagurus lagurus based on the sequence data of cytochrome b and three nuclear genes. All available genetic data indicate that M. mongolicus includes two divergent genetic lineages, which should be recognized as distinct species: M. mongolicus (East Mongolia, Khentii) and M. alpinus (Khangai and adjacent areas). Both M. maximowiczii and M. limnophilus are represented in Mongolia by specific haplogroups of the intraspecies level. Nuclear, mitochondrial and chromosomal data support strong differentiation between Eolagurus luteus and E. przewalskii.

A theoretical model for high-T c superconductivity is presented based on electron pairing due to their interaction with two-level or multi-level tunneling units (TU's) present in high-T c materials. TU's were found experimentally in YBa2Cu3O 7-δ, Bi2CaSr2Cu2O8 , Tl2CaBa2Cu2O8 and in Tl2CaBa2CuO6 . The TU's have specific directions of orientation with respect to the crystal axis and hence cause a strongly anisotropic scattering of the conduction electrons and a strongly anisotropic gap function Δ(k) with wave vector k. For the weak coupling case we obtain, (i) an analytically derived Δ(k) which has a linear combination of s-wave and dx2-y2-wave symmetry with nodes in Δ(k), (ii) a high-T c determined by the elastic interaction potential between the TU's, (iii) an isotope effect consistent with experiment, (iv) a large uniaxial pressure p dependence of T c for YBa2Cu3O 7-δ close to optimal oxygen doping and (dT c /dpa) ≈ -(dT c /dpb) where Pa and Pb are the pressures in the a and b directions, (v) a quantitative agreement with experiment for dT c /dPi (i = a, b) when we use the elastic constant. The recently observed d ± s wave pairing in twinned YBa2Cu3O 7-δ, with a reversal of the sign of s-wave component across the twin boundary, is also in agreement with our model.

The symmetry of the gap function is derived for a system in which the conduction electrons are scattered by elastically interacting tunneling units, causing pairing and superconductivity. For specific examples of tunneling units found in experiments on a number of high T c materials we obtain; (i) a strongly anisotropic effective electron-electron interaction due to the anisotropic coupling to the tunneling units; (ii) a strongly anisotropic gap in k -space even for a spherical fermi surface; (iii) a high transition temperature; (iv) a gap function with nodes and a combination of s and d x 2 − y 2 symmetry.