Koban culture genome-wide and archeological data open the bridge between Bronze and Iron Ages in the North Caucasus.

The North Caucasus played a key role during the ancient colonization of Eurasia and the formation of its cultural and genetic ancestry. Previous archeogenetic studies described a relative genetic and cultural continuity of ancient Caucasus societies, since the Eneolithic period. The Koban culture, which formed in the Late Bronze Age on the North Caucasian highlands, is considered as a cultural "bridge" between the ancient and modern autochthonous peoples of the Caucasus. Here, we discuss the place of this archeological culture and its representatives in the genetic orbit of Caucasian cultures using genome-wide SNP data from five individuals of the Koban culture and one individual of the early Alanic culture as well as previously published genomic data of ancient and modern North Caucasus individuals. Ancient DNA analysis shows that an ancient individual from Klin-Yar III, who was previously described as male, was in fact a female. Additional studies on well-preserved ancient human specimens are necessary to determine the level of local mobility and kinship between individuals in ancient societies of North Caucasus. Further studies with a larger sample size will allow us gain a deeper understanding of this topic.

Genetic Diversity of Common Olive (Olea europaea L.) Cultivars from Nikita Botanical Gardens Collection Revealed Using RAD-Seq Method.

In different countries, interest in the commercial cultivation of the olive has recently greatly increased, which has led to the expansion of its range. The Crimean Peninsula is the northern limit of the common olive (Olea europaea L.) range. A unique collection of common olive's cultivars and hybrids has been collected in the Nikitsky Botanical Gardens (NBG). The aim of this study was to assess the genetic diversity of 151 samples (total of several biological replicates of 46 olive cultivars including 29 introduced and 11 indigenous genotypes) using the ddRAD sequencing method. Structural analysis showed that the studied samples are divided into ten groups, each of which mainly includes cultivars of the same origin. Cultivars introduced to the Crimean Peninsula from different regions formed separate groups, while local cultivars joined different groups depending on their origin. Cultivars of Crimean origin contain admixtures of mainly Italian and Caucasian cultivars' genotypes. Our study showed that the significant number of Crimean cultivars contains an admixture of the Italian cultivar "Coreggiolo". Genetic analysis confirmed the synonymy for the cv. "Otur" and "Nikitskaya 2", but not for the other four putative synonyms. Our results revealed the genetic diversity of the olive collection of NBG and provided references for future research studies, especially in selection studies for breeding programs.

Ancient DNA of the Don-Hares Assumes the Existence of Two Distinct Mitochondrial Clades in Northeast Asia.

Paleoclimatic changes during the Pleistocene-Holocene transition is suggested as a main factor that led to species extinction, including the woolly mammoth (Mammuthus primigenius), Steller's sea cow (Hydrodamalis gigas) and the Don-hare (Lepus tanaiticus). These species inhabited the territory of Eurasia during the Holocene, but eventually went extinct. The Don-hare is an extinct species of the genus Lepus (Leporidae, Lagomorpha), which lived in the Late Pleistocene-Early Holocene in Eastern Europe and Northern Asia. For a long time, the Don-hare was considered a separate species, but at the same time, its species status was disputed, taking into account both morphological data and mitochondrial DNA. In this study, mitochondrial genomes of five Don-hares, whose remains were found on the territory of Northeastern Eurasia were reconstructed. Firstly, we confirm the phylogenetic proximity of the "young" specimens of Don-hare and mountain or white hare, and secondly, that samples older than 39 Kya form a completely distinct mitochondrial clade.

Ancient DNA Reveals Maternal Philopatry of the Northeast Eurasian Brown Bear (Ursus arctos) Population during the Holocene.

Significant palaeoecological and paleoclimatic changes that took place during Late Pleistocene-Early Holocene transition are considered important factors that led to megafauna extinctions. Unlike many other species, the brown bear (Ursus arctos) has survived this geological time. Despite the fact that several mitochondrial DNA clades of brown bears became extinct at the end of the Pleistocene, this species is still widely distributed in Northeast Eurasia. Here, using the ancient DNA analysis of a brown bear individual that inhabited Northeast Asia in the Middle Holocene (3460 ± 40 years BP) and comparative phylogenetic analysis, we show a significant mitochondrial DNA similarity of the studied specimen with modern brown bears inhabiting Yakutia and Chukotka. In this study, we clearly demonstrate the maternal philopatry of the Northeastern Eurasian U. arctos population during the several thousand years of the Holocene.

Genomic Signatures of Freshwater Adaptation in Pacific Herring (Clupea pallasii).

Pacific herring (Clupea pallasii) is an essential target of commercial fishing in the North Pacific Ocean. Previous studies have suggested the existence of marine and lake ecological forms of this species within its range. The lake ecological form of herring has a shortened life cycle, spending the winter and spawning in brackish waters near the shoreline without long migrations for feeding; it also has a relatively smaller body size than the marine form. Genetic-based studies have shown that brackish water Pacific herring not only can be distinguished as a separate lake ecological form but possibly has its genetic legacy. Here, as part of an ongoing study, using ddRAD-sequencing data for marine and lake ecological forms from a total of 54 individuals and methods of comparative bioinformatics, we describe genomic signatures of freshwater adaptivity in Pacific herring. In total, 253 genes containing discriminating SNPs were found, and part of those genes was organized into genome clusters, also known as "genomic islands of divergence". Moreover, the Tajima's D test showed that these loci are under directional selection in the lake populations of the Pacific herring. Yet, most discriminating loci between the lake and marine ecological forms of Pacific herring do not intersect (by gene name) with those in other known marine fish species with known freshwater/brackish populations. However, some are associated with the same physiological trait-osmoregulation.

Intergeneric hybridization of two stickleback species leads to introgression of membrane-associated genes and invasive TE expansion.

Interspecific hybridization has occurred relatively frequently during the evolution of vertebrates. This process usually abolishes reproductive isolation between the parental species. Moreover, it results in the exchange of genetic material and can lead to hybridogenic speciation. Hybridization between species has predominately been observed at the interspecific level, whereas intergeneric hybridization is rarer. Here, using whole-genome sequencing analysis, we describe clear and reliable signals of intergeneric introgression between the three-spined stickleback (Gasterosteus aculeatus) and its distant mostly freshwater relative the nine-spined stickleback (Pungitius pungitius) that inhabit northwestern Russia. Through comparative analysis, we demonstrate that such introgression phenomena apparently take place in the moderate-salinity White Sea basin, although it is not detected in Japanese sea stickleback populations. Bioinformatical analysis of the sites influenced by introgression showed that they are located near transposable elements, whereas those in protein-coding sequences are mostly found in membrane-associated and alternative splicing-related genes.

A de novo genome assembly of cultivated Prunus persica cv. 'Sovetskiy'.

Prunus persica is one of the main stone fruit crops in Crimea and southern Russia. The P. persica genome has recently been sequenced and annotated in good quality. However, for a deeper assessment of the peach genome, it is necessary to include in the research other cultivars that are in the collection of the Nikitsky Botanical Garden. The cultivars of the Nikitsky Botanical Garden are unique and differ from Western European and American ones, as they are derived from cultivars and forms originating from Central Asian, North Caucasian, Transcaucasian and Eastern European countries. In this paper, we present the assembly of the P. persica cv. 'Sovetskiy' genome obtained using Oxford Nanopore long reads and Illumina short reads by hybrid assembly methods. The assembled genome of P. persica cv. 'Sovetskiy' is 206.26 MB in 226 scaffolds, with N50 24 Mb, including 8 chromosomes. It contains 27140 coding genes, 26973 (99.38%) of which are annotated in at least one functional database. More than 36.05% of the genome regions were identified as repeating elements.

Non-GCB Diffuse Large B-Cell Lymphoma With an Atypical Disease Course: A Case Report and Clinical Exome Analysis.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid tumor among other non-Hodgkin lymphomas (30-40% of all cases). This type of lymphoma is characterized by significant differences in treatment response and the heterogeneity of clinical traits. Approximately 60% of patients are cured using standard chemotherapy (CT), while in 10-15% of cases, the tumor is characterized by an extremely aggressive course and resistance to even the most high-dose programs with autologous stem cell transplantation (auto-SCT). The activated B-cell (ABC) subtype of DLBCL is characterized by poor prognosis. Here, we describe a clinical case of diffuse ABC-DLBCL with an atypical disease course. Complete remission was achieved after four courses of CT, followed by autologous hematopoietic stem cell transplantation (auto-HSCT). However, early relapse occurred 2 months after the completion of treatment. According to the results of cytogenetic studies, significant chromosome breakdowns were observed. Exome sequencing allowed for the detection of several novel mutations that affect components of the NOTCH2 and NF-κB signaling pathways, a number of epigenetic regulators (KMT2D, CREBBP, EP300, ARID1A, MEF2B), as well as members of the immunoglobulin superfamily (CD58 and CD70). Whether these mutations were the result of therapy or were originally present in the lymphoid tumor remains unclear. Nevertheless, the introduction of genomic technologies into clinical practice is important for making a diagnosis and developing a DLBCL treatment regimen with the use of targeted drugs.

Caucasian treasure: Genomics sheds light on the evolution of half-extinct Sevan trout, Salmo ischchan, species flock.

Five ecologically and phenotypically divergent ecomorphs of the genus Salmo are known from a landlocked alpine lake in the Caucasus, Lake Sevan. It is an example of sympatric diversification within a species-rich lineage with predominate mode of speciation being allopatric. The diversification of Sevan trouts was accompanied by spawning resource partitioning. Four lacustrine ecomorphs with different temporal-spatial spawning strategies and divergent morphology and coloration evolved along with a fifth ecomorph, brook trout, inhabiting the tributaries. Unfortunately, the Sevan trout diversity was almost destroyed by human activity, with two ecomorphs becoming extinct in the 1980s. We performed reconstruction of the evolutionary history of Sevan trouts based on high-throughput sequencing of both contemporary and historical DNA (∼ 50 y.o.) of all Sevan trout ecomorphs. Our study of complete mitogenomes along with genome-wide SNP data revealed the monophyly of four lacustrine ecomorphs and local brook trout, all derived from the anadromous form Caspian salmon, S. caspius. The species tree suggests a scenario of stepwise evolution from riverine to lacustrine spawning. Three genomic clusters were revealed, of which two refer to the riverine and lacustrine spawners within the flock of Sevan trouts (with FST value = 0.069). A few SNP outliers under selection were discovered that could be responsible for assortative mating based on visual recognition. The Holocene climatic oscillations and the desiccation of tributaries could have played an important role in the origin of lacustrine spawning. The relationships between lacustrine ecomorphs were not yet fully resolved. This radiation warrants further investigation.

Genetic structure of marine and lake forms of Pacific herring Clupea pallasii.

The Pacific herring (Clupea pallasii) is one of the most important species in the commercial fisheries distributed in the North Pacific Ocean and the northeastern European seas. This teleost has marine and lake ecological forms a long its distribution in the Holarctic. However, the level of genetic differentiation between these two forms is not well known. In the present study, we used ddRAD-sequencing to genotype 54 specimens from twelve wild Pacific herring populations from the Kara Sea and the Russian part of the northwestern Pacific Ocean for unveiling the genetic structure of Pacific herring. We found that the Kara Sea population is significantly distinct from Pacific Ocean populations. It was demonstrated that lake populations of Pacific herring differ from one another as well as from marine specimens. Our results show that fresh and brackish water Pacific herring, which inhabit lakes, can be distinguished as a separate lake ecological form. Moreover, we demonstrate that each observed lake Pacific herring population has its own and unique genetic legacy.

The complete chloroplast genome sequence of cultivated Prunus persica cv. 'Sovetskiy'.

The peach (Prunus persica L. Batsch) is one of the important stone fruit crops in the Crimea Peninsula and the southern part of Russia. The complete chloroplast genome of the peach cultivar 'Sovetskiy' is published in this paper. The chloroplast genome size is 157,756 bp. It contains 126 genes, including 81 protein-coding genes (PCGs), eight ribosomal RNA (rRNA) genes, and 37 transfer RNA (tRNA) genes. The chloroplast genome also contains a large single-copy region of 85,960 bp, a small single-copy (SSC) region of 19,045 bp, and two inverted repeats regions of 26,375 bp and 26,372 bp. The overall base composition of the genome in descending order is 31.2% - A, 32.1% - T, 18.7% - C, and 18.0% - G. The total GC content of the chloroplast genome is 36.7%. Maximum-likelihood phylogenetic analysis involving nine chloroplast genomes of the Prunus genus revealed a separate cluster for P. persica and its possible landrace - P. ferganensis.

Steller's sea cow genome suggests this species began going extinct before the arrival of Paleolithic humans.

Anthropogenic activity is the top factor directly related to the extinction of several animal species. The last Steller's sea cow (Hydrodamalis gigas) population on the Commander Islands (Russia) was wiped out in the second half of the 18th century due to sailors and fur traders hunting it for the meat and fat. However, new data suggests that the extinction process of this species began much earlier. Here, we present a nuclear de novo assembled genome of H. gigas with a 25.4× depth coverage. Our results demonstrate that the heterozygosity of the last population of this animal is low and comparable to the last woolly mammoth population that inhabited Wrangel Island 4000 years ago. Besides, as a matter of consideration, our findings also demonstrate that the extinction of this marine mammal starts along the North Pacific coastal line much earlier than the first Paleolithic humans arrived in the Bering sea region.

Genomic evidence supports the introgression between two sympatric stickleback species inhabiting the White Sea basin.

Interspecies hybridization is driven by a complex interplay of factors where introgression plays an important role. In the present study, the transfer of genetic material, between two quite distant fish species from different genera, through spontaneous hybridization was documented with dedicated molecular and bioinformatics tools. We investigate the genomic landscape of putative stickleback-relative introgression by carefully analyzing the tractable transposable elements (TE) on the admixed genome of some individuals of two sympatric stickleback species inhabiting northwestern Russia, namely the three-spined (Gasterosteus aculeatus) and the nine-spined (Pungitius pungitius) sticklebacks. Our data revealed that unique TE amplification types exist, supporting our proposed hypothesis that infers on the interspecific introgression. By running a restriction site-associated DNA sequencing (RAD-Seq) with eight samples of G. aculeatus and P. pungitius and subjecting further the results to a contrasting analysis by variated bioinformatic tools, we identified the related introgression-linked markers. The admixture nature observed in a single sample of the nine-spined stickleback demonstrated the possible traces of remote introgression between these two species. Our work reveals the potential that introgression has on providing particular variants at a high-frequency speed while linking blocks of sequence with multiple functional mutations. However, even though our results are of significant interest, an increased number of samples displaying the introgression are required to further ascertain our conclusions.

First report of fig mosaic virus on fig in Russia.

Fig mosaic virus (FMV) (genus Emaravirus in the family Fimoviridae) is considered the etiological agent of fig mosaic disease (FMD) that is recorded in most of the fig growing areas with an average global infection rate of 33%. The multipartite FMV genome is comprised of six negative monocistronic ssRNAs, each of which is separately encapsidated (Preising et al. 2020). Although FMD-like symptoms, which include mosaic, chlorotic ringspots, and oak leaf patterns, were observed in approximately a third of 400 fig accessions in the Nikita Botanical Gardens, Yalta, Russia (Mitrofanova et al. 2016), FMV has not been identified as the causal agent of the disease. In June of 2020, total RNA was isolated from symptomatic leaves of 59 thirty two-year-old trees representing 31 local and 27 introduced Ficus carica L. cultivars and a single F. pseudocarica Miq. tree using RNeasy Plant Mini kit (Qiagen, USA). FMV was tested by RT-PCR using primer sets E5 (Elbeaino et al. 2009) and EMARAVGP (Walia et al. 2009), which amplify a 302-bp fragment of RNA1 and a 468-bp fragment of RNA2, respectively. PCR products of the expected sizes were generated in all samples, indicating a high FMV incidence in the plantings. The genome sequences of FMV isolates from F. carica cvs. Bleuet, Kraps di Hersh, Smena, Temri, and F. pseudocarica (Fig. S1) were determined by high-throughput sequencing on MiSec Illumina platform. Double-stranded RNA was isolated from FMV-positive leaves using Viral Gene-spin™ Viral DNA/RNA Extraction Kit (iNtRON, Korea), followed by cDNA library preparation with the NEBNext® Ultra™ II RNA Library Prep Kit (New England Biolabs, USA). In average, 695,000 quality-filtered 150 bp pair-ended reads per a library were produced and used in a de novo assembly using metaSpades program version 3.14 (Nurk et al. 2017). In each of five samples, BLASTn analysis found six FMV-related contigs. The contigs spanned 99 to 100% of corresponding genomic segments of the most closely related isolates. In addition to FMV, fig cryptic virus-related contigs were also detected in some samples. The FMV contigs covering RNA1 to RNA6 had the highest identity to corresponding genomic segments of isolates AM941711 (96.5 to 96.6%), FM864225 (94.4 to 94.6%), FM991954 (97.9 to 98.2%), AB697863 (96.4 to 96.6%), AB697879 (93.3 to 93.4%), and AB697895 (95.4 to 97.0%), respectively. Five Russian isolates shared 99.2 to 100% nucleotide sequence identity, depending on the genomic segment. Their sequences were deposited in GenBank under accession numbers MW201216 to MW201230 and MW208662 to MW208676. Phylogenetic analysis of six ORFs showed that ORF1 to ORF3 and ORF6 of the Russian isolates clustered with FMV isolates from Italy while ORF4 grouped with the isolate JTT-Pa (AB697863) from Japan (Fig. S2). ORF5 of the Russian isolates formed a separate cluster with the isolates SB1 and SB2 from Serbia and JTT-Vi from Japan (AB697879 to AB697884). Incongruency of phylogenetic relationship among the genomic segments suggests reassortment among ancestors of the Russian FMV isolates. In addition, similar to the SB1, SB2 and JTT-Vi, ORF5 of the Russian isolates encodes a protein of 486 amino acid (aa) residues in contrast to the corresponding protein of Italian isolates consisting of 502 aa. To the best of our knowledge, this is the first report of FMV in Russia. This finding not only expands the information on the geographical distribution of FMV, but also extends knowledge on F. pseudocarica as a natural host of the virus.

The Biomarker and Therapeutic Potential of Circular Rnas in Schizophrenia.

Circular RNAs (circRNAs) are endogenous, single-stranded, most frequently non-coding RNA (ncRNA) molecules that play a significant role in gene expression regulation. Circular RNAs can affect microRNA functionality, interact with RNA-binding proteins (RBPs), translate proteins by themselves, and directly or indirectly modulate gene expression during different cellular processes. The affected expression of circRNAs, as well as their targets, can trigger a cascade of events in the genetic regulatory network causing pathological conditions. Recent studies have shown that altered circular RNA expression patterns could be used as biomarkers in psychiatric diseases, including schizophrenia (SZ); moreover, circular RNAs together with other cell molecules could provide new insight into mechanisms of this disorder. In this review, we focus on the role of circular RNAs in the pathogenesis of SZ and analyze their biomarker and therapeutic potential in this disorder.

A new strain group of common carp: The genetic differences and admixture events between Cyprinus carpio breeds.

Common carp (Cyprinus carpio) has an outstanding economic importance in freshwater aquaculture due to its high adaptive capacity to both food and environment. In fact, it is the third most farmed fish species worldwide according to the Food and Agriculture Organization. More than four million tons of common carp are produced annually in aquaculture, and more than a hundred thousand tons are caught from the wild. Historically, the common carp was also the first fish species to be domesticated in ancient China, and now, there is a huge variety of domestic carp strains worldwide. In the present study, we used double digestion restriction site-associated DNA sequencing to genotype several European common carp strains and showed that they are divided into two distinct groups. One of them includes central European common carp strains as well as Ponto-Caspian wild common carp populations, whereas the other group contains several common carp strains that originated in the Soviet Union, mostly as cold-resistant strains. We believe that breeding with wild Amur carp and subsequent selection of the hybrids for resistance to adverse environmental conditions was the attribute of the second group. We assessed the contribution of wild Amur carp inheritance to the common carp strains and discovered discriminating genes, which differed in allele frequencies between groups. Taken together, our results improve our current understanding of the genetic variability of common carp, namely the structure of natural and artificial carp populations, and the contribution of wild carp traits to domestic strains.

Molecular phylogeny of one extinct and two critically endangered Central Asian sturgeon species (genus Pseudoscaphirhynchus) based on their mitochondrial genomes.

The enigmatic and poorly studied sturgeon genus Pseudoscaphirhynchus (Scaphirhynchinae: Acipenseridae) comprises three species: the Amu Darya shovelnose sturgeon (Pseudoscaphirhynchus kaufmanni (Bogdanow)), dwarf Amu Darya shovelnose sturgeon P. hermanni (Kessler), and Syr Darya shovelnose sturgeon (P. fedtschenkoi (Bogdanow). Two species - P. hermanni and P. kaufmanni - are critically endangered due to the Aral Sea area ecological disaster, caused by massive water use for irrigation to support cotton agriculture, subsequent pesticide pollution and habitat degradation. For another species - P. fedtschenkoi - no sightings have been reported since 1960-s and it is believed to be extinct, both in nature and in captivity. In this study, complete mitochondrial (mt) genomes of these three species of Pseudoscaphirhynchus were characterized using Illumina and Sanger sequencing platforms. Phylogenetic analyses showed the significant divergence between Amu Darya and Syr Darya freshwater sturgeons and supported the monophyletic origin of the Pseudoscaphirhynchus species. We confirmed that two sympatric Amu Darya species P. kaufmanni and P. hermanni form a single genetic cluster, which may require further morphological and genetic study to assess possible hybridization, intraspecific variation and taxonomic status and to develop conservation measures to protect these unique fishes.

A partial genome assembly of the miniature parasitoid wasp, Megaphragma amalphitanum.

Body size reduction, also known as miniaturization, is an important evolutionary process that affects a number of physiological and phenotypic traits and helps animals conquer new ecological niches. However, this process is poorly understood at the molecular level. Here, we report genomic and transcriptomic features of arguably the smallest known insect-the parasitoid wasp, Megaphragma amalphitanum (Hymenoptera: Trichogrammatidae). In contrast to expectations, we find that the genome and transcriptome sizes of this parasitoid wasp are comparable to other members of the Chalcidoidea superfamily. Moreover, compared to other chalcid wasps the gene content of M. amalphitanum is remarkably conserved. Intriguingly, we observed significant changes in M. amalphitanum transposable element dynamics over time, in which an initial burst was followed by suppression of activity, possibly due to a recent reinforcement of the genome defense machinery. Overall, while the M. amalphitanum genomic data reveal certain features that may be linked to the unusual biological properties of this organism, miniaturization is not associated with a large decrease in genome complexity.

Phylogenetic position of the presumably extinct slender-billed curlew, Numenius tenuirostris.

The high-capacity DNA analysis of museum samples opens new opportunities, associated with the investigation of extinct species evolution. Here, the complete mitochondrial genome of the presumably extinct bird species, the slender-billed curlew Numenius tenuirostris (Charadriiformes: Scolopacidae) is presented. Our results showed that mitochondrial DNA (mtDNA) is 16,705 base pairs (bp) in length and contain 13 protein-coding genes, two rRNA genes, and 22 tRNA genes. The overall base composition of the genome is 30.8% - A, 29.8% - C, 25.4% - T, 14.0% - G, and without a significant GC bias of 43.7%. Phylogenetic analyses based on the cytochrome B (cytB) gene and the whole mtDNA sequences revealed that N. tenuirostris had a close genetic relationship to Eurasian curlew (N. arquata), Far Eastern curlew (N. madagascariensis), and long-billed curlew - N. americanus. Besides, it reveals that Numenius genus is genetically distant from other Scolopacidae taxons. Together, these results provide a clear genetic perspective into the speciation process among the curlew genus members and points to a clear taxonomic position of N. tenuirostris.