The final part of our series of studies reports the results of a pilot study of a clinical case (patient K.), indicating that therapy enabling reconstruction of the genome of hematopoietic stem cells (HSCs) reduces the frequency of SNPs in exons of the genes associated with clonal hematopoiesis of uncertain potential in a patient with a neuroendocrine tumor of the small intestine in the terminal stage of progression. The fundamental principles of the therapy were as follows. Control samples of peripheral blood mononuclear cells (baseline) were collected from the patient. CD34+ HSCs were then mobilized and collected. The HSC genome was modified using a technology enabling ex vivo correction of the nucleotide sequences of DNA chromosomes of poorly differentiated hematopoietic progenitor cells. For this purpose, the collected leukocyte suspension enriched with CD34+ HSCs was treated with fragmented deproteinized genomic DNA obtained from approximately 100 young healthy women in labor (hDNA^gr). The patient was reinfused intravenously with the treated cells. Five days before reinfusion, the patient received immunosuppressive therapy. Samples of peripheral blood mononuclear cells were also collected 4, 8, 12, and 27 months after the therapeutic intervention. Full-exome sequencing of DNA isolated from selected cell samples was performed. A group of commonly accepted clonal hematopoiesis genes was selected as a criterion demonstrating changes in the genome. The following multiplex panels were used at the initial time point as well as time points after 4, 8, and 12 months: MGIEasy Exome Capture V5 Probe set, Roche KAPA HyperExome, Nanodigmbio NEXome Plus Panel v1.0, covering the entire exome and non-coding regions of the analyzed genes adjacent to exons with ~100× coverage. A ~1000× coated panel (Nanodigmbio NanOnco Plus Panel v3.0), including the genes with mutant alleles identified at the initial time point, was used to verify the identified mutations and more accurately determine their proportions in readings at the last stage of the analysis (27 months after the therapy). Whole-exome sequencing of hDNA^gr (Roche KAPA HyperExome), which is used to reconstruct the genome of HSCs whose fragments collectively constitute the complete human genome, was also performed. Although the analysis of readings of whole-exome sequencing of DNA isolated from blood samples after treatment did not reveal any currently known signs of clonal hematopoiesis with uncertain potential in the patient K., we found a significant, within the framework of the selected criterion, decrease in the frequency range of SNPs to 18 % by 27 months of follow-up in 15 % cases of the heterozygous alleles (DNMT1, SF3B1(1–2)). Subsequent analysis of the frequency of occurrence of controlled SNPs and the corresponding data on the depth of their sequencing, performed using the All-FIT algorithm, indicates that by the 27th month of follow-up, the proportion of cells carrying the basic set of SNPs significantly decreases by 12 % (confidence interval (CI) = 5–16 %). In other words, in a mixture of cells heterozygous for this SNP, a population of cells carrying a homozygote without an SNP appears. Our findings may indicate that a significant proportion of cells underwent correction of the SNP to an alternative allele, and this correction was associated with the treatment of the original HSCs with hDNA^gr. The detected changes in the group of clonal hematopoiesis genes suggest the possibility of correcting other loci throughout the HSCs genome. Therefore, the clinical manifestations in the development of the disease show a pronounced positive trend, which has persisted for four years, until present. It is assumed that the positive clinical outcome after therapy with reconstructed hematopoietic stem cells is associated with an increase in the regenerative potential of HSCs, which resulted from the genetic correction of unfavorable mutations in the HSCs genome.

The impact of psychosocial chronic stress on mammalian oocyte maturation, fertilization and early stages of embryonic development remains poorly understood. This study addresses the effects of chronic psychosocial stress on the reproductive outcome in female mice, i. e. the development of in vitro- and in vivo-derived embryos. The model of chronic stress used in the study comprised a 21-day protocol consisting of a period of social isolation followed by the overcrowding. Two experiments were conducted, varying in the type of fertilization. In experiment 1, female mice were stressed at the folliculogenesis stages; then oocyte maturation and in vitro fertilization were performed, and the early development of the in vitro-derived embryos was studied. Experiment 2 differed in that fertilization was performed in vivo, and the resulting in vivo-derived embryos were cultured in vitro since the two-cell stage. To assess preimplantation embryo development, blastocysts were fixed, stained with the TUNEL/DAPI method and analyzed using fluorescence microscopy, i. e. the number of interphase nuclei and the apoptosis index were estimated. The results of Experiment 1 showed that chronic stress did not affect oocyte maturation or their fertilization capacity. However, embryos from the stress group contained fewer interphase nuclei (p < 0.001), which points to a lower cleavage rate. Meanwhile, the apoptosis rate in these blastocysts was comparable to controls. Experiment 2 showed that chronic stress caused a decrease in the proportion of embryos that achieved the blastocyst stage during the culture period and an increase in the proportion of morulae (p < 0.01), as well as a decrease in the number of interphase nuclei in blastocysts (p < 0.001). Experiments demonstrated that the chronic psychosocial stress exerts a moderate but significant effect on early embryonic development, primarily via the reduced proliferative activity of embryonic cells. These results obtained in mice have a translational value for reproductive medicine and highlight the importance of maternal stress when analyzing ART outcomes.

Interspecific hybridization plays a crucial role in tomato (Solanum lycopersicum L.) breeding for introducing beneficial traits from wild relatives, such as resistance to biotic and abiotic stress. Sticky nightshade (Solanum sisymbriifolium Lam.) is a promising source for the introgression of desirable traits. Reports on hybridization between S. lycopersicum and S. sisymbriifolium remain contradictory, differently describing the progeny as doubled haploids or interspecific hybrids. In the present study, we clarify the nature of the progeny derived from hybridization between S. lycopersicum and S. sisymbriifolium by analyzing the early stages of ovule development and characterizing the morphological and cytogenetic features of the resulting plants. Interspecific hybridization between S. lycopersicum and S. sisymbriifolium encounters postzygotic reproductive barriers. Only a small proportion of developing ovules in male-sterile tomato lines, whether self-pollinated or pollinated with S. sisymbriifolium followed the normal developmental pathway. In most cases, either ovule development was arrested, or parthenocarpic seed-like bodies formed instead of normal seeds. Embryo rescue enabled the recovery of 12 plants resulting from interspecific hybridization of S. lycopersicum and S. sisymbriifolium. Morphologically, the plants closely resembled the S. lycopersicum parent, although they displayed several traits distinctive from those of the parental tomato lines. Notably, yellow-orange mature fruits developed in progeny from the cross of green-fruited S. lycopersicum and red-fruited S. sisymbriifolium. Analysis of chromosome numbers in root meristems revealed mixoploidy (2n = 16–26), and meiotic analysis during microsporogenesis showed multiple aberrations in meiosis. Thus, comprehensive embryological, morphological, and cytogenetic analyses provide evidence for the hybrid origin of the obtained plants. This confirms the possibility of overcoming postzygotic barriers between these species and opens avenues for the utilization of S. sisymbriifolium in tomato breeding programs.

According to the latest data, 55 species of the genus Elymus are distributed in Russia, carrying three subgenomic combinations (StH, StY, and StHY). Among them, the StY-genomic group comprises only 10 species, with varying degrees of understanding of their evolutionary relationships. Ancestral taxa of the genus Pseudoroegneria donated the St subgenome to all modern species of the genus Elymus. The StY-genomic group of species possesses an additional Y subgenome of unknown origin, which, according to some data, is close to the St subgenome. We studied the phylogenetic relationships between StY-genomic species from Russia, five species of the genus Pseudoroegneria, and five species of the genus Hordeum from the NCBI GenBank by comparing the nucleotide sequences of the nuclear gene GBSS1 from exons 9 to 14. One of the main objectives was a comparative analysis of phylogenetic patterns based on (i) more conservative exons and (ii) introns that do not encode the amino acid sequences of the enzyme. All gene variants from the St subgenomes of the studied species are divided into three clusters according to three marker groups of nucleotide sequence of clones in the genus Pseudoroegneria: Central Asian (St₁) with the reference species P. strigosa, North American (St₂) with the marker species P. spicata, and Middle Eastern (St₃) with two species, P. tauri and P. libanotica, to which the Eastern European species P. stipifolia gravitates. The H subgenome, originating from ancestral taxa of the genus Hordeum (Critesion), was not detected in any of the studied species. The cluster of Y subgenome in the “introns” variant is generally visually less differentiated than in the “exons” variant. This fact contradicts the established notion that gene regions responsible for the synthesis of enzymatic molecules are more conserved. Among the most notable characteristics in the comparison of nucleotide sequences is the presence of a special Far Eastern race of E. gmelinii with St₃ sequences instead of St₁ and the location of the sequences of all clones of the North Kazakhstan accession E. fedtschenkoi KSA-0935 in the St₂ cluster instead of St₃.

Plants of the genus Miscanthus are a promising perennial energy crop, combining high biomass productivity, resistance to abiotic stress, and low agricultural technology requirements. This review summarizes recent advances in genomic and transcriptomic studies of the molecular genetic mechanisms underlying the economically valuable traits of Miscanthus. Data on whole-genome assemblies of key species – M. sinensis (Msi), M. sacchariflorus (Msa), M. floridulus (Mfl), and M. lutarioriparius (Mlu) – are presented using various technologies (Illumina, PacBio, Oxford Nanopore, Hi-C). Genomic studies have revealed the complex evolution of the genus, including paleoallopolyploidy, chromosomal fusions, and duplications, which accounts for the high genetic diversity of these species. Their genome assemblies at the complete chromosome level have become the basis for comparative genomics, establishing taxonomic relationships (including the recognition of Mlu as a subspecies of Msa and Mfl as a subtype of Msi), and studying synteny with related crops such as sorghum. The information on the Miscanthus genome allows for the complete and accurate identification of a set of genes targeting breeding for the most important biotechnological traits. At the same time, the commercial hybrid M. × giganteus (M × g) is characterized by extremely low levels of genetic polymorphism, making it vulnerable to pathogens and climate fluctuations. The integration of genetic polymorphism data, phylogeography, and functional annotation of genomes opens up opportunities for the development of new, productive, and environmentally friendly Miscanthus varieties through interspecific crossings, ploidy modification, and genetic engineering. These advances contribute to the optimization of the biotechnological potential of Miscanthus for the production of biofuels and other biomaterials and the restoration of degraded lands.

Storage of potato tubers intended for further processing is complicated by their cold-induced sweetening (CIS). Enzymatic hydrolysis of sucrose into glucose and fructose occurs at low temperatures. The resulting high hexose content adversely affects the quality of processed potato products such as chips and fries and promotes the formation of acrylamide, which is a neurotoxin and carcinogen. During CIS, sucrose hydrolysis is catalyzed by vacuolar invertase encoded by the StPain-1 gene. Previous studies have shown that suppression of the enzyme activity confers potato resistance to CIS without reducing the nutritional value of tubers. In this study, CRISPR/Cas9 technology was used to generate Solanum tuberosum L. cv. Fritella plants with a knockout of StPain-1. Two binary vectors based on pKSE401 were constructed (Vector A and Vector B), each carrying two gRNAs targeting exon 1 (sgRNA-P1.A or sgRNA-P1.B) and exon 3 (sgRNA-P3.A or sgRNA-P3.B). Editing efficiency with each gRNA was evaluated through next-generation sequencing (NGS). Transformation with Vector A produced 48 transformants, 22 of which carried knockouts in all StPain-1 alleles. Transformation with Vector B yielded 26 transformants, including 10 plants with complete StPain-1 knockout. Chips made from tubers of nine edited Fritella plants demonstrated reduced vacuolar invertase activity: chips from StPain-1 knockout lines were lighter compared to the non-edited control sample. Quantitative assessment of glucose, fructose, and sucrose levels, as well as StPain-1 mRNA expression in tubers of four selected transformants (two per vector), confirmed enzyme inactivation. The resulting plants exhibit increased resistance to cold-induced sweetening and can be used as a promising source of nonfunctional StPain-1 alleles for breeding new potato varieties.

Fusarium oxysporum (Fo) is among the most dangerous soilborne pathogens, causing Fusarium wilt and root rots in over 100 plant species worldwide. Some pathogen strains can also infect immunocompromised animals and humans. Consequently, studying the molecular mechanisms associated with pathogen virulence and the plant immune response at different stages of disease development is of paramount importance. The process of host recognition by the pathogen and all stages of the infection process involve a wide repertoire of specific signaling molecules, effector proteins, receptor complexes, as well as interconnected and overlapping signaling pathways. Plants, in turn, have evolved a complex defense system to counter this attack: they also possess intricate molecular-level mechanisms that, triggered by pathogen assault, transmit signals to activate a defensive response. In this review, we examine the main currently known molecular mechanisms of Fo-host interaction within the plant-pathogen system: from plant detection and directed hyphal growth driven by chemotropism, to complex interactions at the level of immune response and specific fungal tactics for its suppression. The review includes sections dedicated to the dynamics of plant infection, pathogen genome organization and its genomic diversity, plant immune response and pathogen suppression tactics, as well as an analysis of the main known effector molecules of the pathogen and associated transcription factors. Special emphasis is put on the special form of Fo that infects flax (Linum usitatissimum L.).

Rice, as a key model in the study of agroecosystem genomics, is the focus of research meant to address the challenges of producing sufficient food for the growing global population. In breeding programs developing new varieties, improving the physicochemical properties of the grain is crucial. Based on the analysis of national and international research, this article presents information on new molecular genetic methodologies and advances in the development of new valuable rice genotypes using genome sequencing data. Continuous enrichment of rice germplasm at global breeding centers is achieved through the use of highly effective approaches employing postgenomic and cellular technologies in combination with traditional phenotyping methods. This review examines the achievements of molecular genetic research in rice, focusing on valuable grain quality traits such as vitreousness (chalkiness) and shape (size). GWAS analysis is widely used in marker-assisted and genomic rice breeding programs. More recently, GBS analysis has been used to identify relationships between phenotype and genotype based on the analysis of bi-parental mapping populations and varietal accessions. The post-genomic research period, focused on the search for candidate genes for valuable quality traits, had started after the genomic reference sequences were obtained. As a result, hundreds of QTLs for the chalkiness trait were discovered across 12 chromosomes, few were accurately mapped or sequenced. By 2018, several major QTLs affecting grain size were sequenced and characterized. For example, the presence of the recessive GS3 allele and the dominant GW7^TFA allele increases the grain length-to-width ratio. In 2023, it was shown that overexpression of OsFIF3 inhibits the expression of FLO2 and SUT1, thereby increasing chalkiness and reducing grain size. This breeding breakthrough is attributed, for example, to the use of non-digital markers for length, width, thickness, and the grain length-to-width ratio, GS3RGS1 and RM505, as selection markers. All research is an ongoing process aimed at achieving the highest possible level of high-quality rice products.

Purple-colored grains of cereal crops are characterized by high antioxidant activity. Anthocyanins, polyphenolic compounds found in the pericarp of their grains, have beneficial effects on human health. However, triticale has not yet developed forms with anthocyanin-rich purple grain color. The aim of this work was to obtain new forms of wheat-rye amphiploids with purple grain color using marker-assisted breeding and to compare their anthocyanin content and productivity indicators. Molecular DNA markers were used to determine the genotype of hybrids produced by triticale Sadko (× Triticosecale Wittmack) and a purple-colored emmer wheat line 27-3/17 (T. dicoccum (Schrank) Schuebl.). Purple-colored F₃ hybrids carried two complementary dominant genes Pp3 and Pp-B1 in a homozygous state responsible for the high content of anthocyanins in the grain. In subsequent generations, the wheat-rye amphiploids had a purple grain color. The total anthocyanin content in the whole grain flour of the hybrids ranged from 36 to 529.3 μg/g. The high content was recorded in sample 2-1-6-6 (529.3 μg/g). Samples 2-1-1-4e, 2-1-5-10a and 2-1-6-4b were at the control level (emmer wheat – 382.6 3 μg/g). The F_5–6 hybrid plants had a typical hexaploid triticale phenotype. The spike length and the number of spikelets exceeded those of emmer wheat. The number of spike grains in the hybrids was less than that in the Sadco triticale averaging at 28.0 and 34.4 in 2024 and 2025, respectively. 1,000 grain weight of purple-grained triticale families in 2025 was comparable to the Sadko maternal form and averaged 47.6 g. The yield per unit area of hybrid families (470 g/m²) in 2025 was higher than that of emmer wheat (306 g/m²), but lower than that of Sadko (584 g/m²). Thus, the breeding material of purple-grained triticale forms was obtained, which in a number of ways is similar to the triticale Sadko maternal form, but differs from the paternal form of the purple grain donor emmer wheat.

The production of emmer hybrids with a high content of anthocyanins in the grains for the production of functional foods is a promising breeding direction. Phenotyping and preliminary assessment of the inheritance of gliadin-coding genes were performed for the most promising purple-grained emmer hybrids obtained previously after a complex three-stage crossing of purple-grained durum wheat (T. durum Desf.) with two different forms of spring emmers (T. dicoccum Schrank): the hybrid naked-grained variety Gremme and the red-grained awnless mutant line k25516. Genotyping hybrids for the storage protein genes in wheat grain, gliadins (Gli), enabled the selection of a purple-grained line that fully inherited gliadin-coding genes from emmer wheat k-25516, and a line inheriting these genes from durum wheat and emmer wheat k-25516. To improve the breeding material, backcrossing of three phenotypically and qualitatively different purple-grained hybrid lines with the parental variety Gremme, which demonstrated the highest yield, was conducted. During the Pp (Purple pericarp) genes selection of the plants in F_2–3 progenies, the use of microsatellite markers located close to Pp genes did not demonstrate reliable linkage to the target genes. The intragenic polymorphic PCR markers made it possible to accurately select plants carrying dominant alleles of two complementarily interacting genes, Pp-B1 and Pp3 in F_2–4. Based on the ease of grain threshing, the plants were selected in F₄. Thus, over two years, using small areas of the greenhouse and marker-controlled selection, a collection consisting of 25 naked and semi-naked spring purple-grained lines of wheat-emmer hybrids, constant in anthocyanin coloration and differing in gliadin-coding genes and other quality traits, was obtained.

Over the past two decades, the introduction of whole-genome sequencing analysis of ancient DNA has led to a breakthrough in archaeogenetic research, significantly expanding our understanding of human genetic history. In this context the Northern Black Sea region during first millennium CE (1–1,000 CE) is of particular relevance, as it remained a hub of intense cultural exchange and migration. Despite its historical importance, ancient genomic data from this period remains scarce, and a comprehensive synthesis of existing findings is lacking. This study presents a systematic review and meta-analysis of published whole-genome sequencing data from 48 ancient samples associated with key archaeological cultures of the region: Late Scythian, Sarmatian, Alan, Bulgar, Saltovo-Mayaki and Chernyakhov. Through the systematization of data, we trace genetic continuity at Late Scythian and Alanian sites relative to preceding populations. Episodes of large-scale migration and population replacement have been documented, most clearly evident in the Sarmatian expansion of the 1st–4th centuries CE, with genetic traces extending from the Urals to the Carpathians. Based on limited evidence, genetic continuity has been identified between representatives of the Chernyakhov culture and early Slavic groups. Through our meta-analysis, we further detect intercultural connections between the Alans, Bulgars, and bearers of the Saltovo-Mayaki culture, whose genetic structure reveals the influence of Caucasian and East Eurasian components. Collectively, these findings underscore the complex genetic landscape of the region, shaped by successive migration waves and multifaceted intercultural contacts. We conclude by outlining key unresolved questions and future directions for archaeogenetic research in the Northern Black Sea region during the first millennium CE.

This study introduces a novel approach for noninvasive prenatal testing (NIPT) of chromosomal abnormalities, based on analysis of epigenetic features in circulating cell-free DNA (cfDNA). The core innovation of our method leverages fundamental differences in chromatin organization between maternal and fetal cells. Specifically, we focused on genomic regions that exhibit open chromatin configuration in maternal blood cells but remain tightly packed in fetal tissues (DNase I hypersensitive sites or DHSs). These epigenetic differences create distinct cfDNA fragmentation signatures that allow selective identification of fetal DNA within the maternal cfDNA pool. The study workflow comprised several key steps: performing genome-wide screening to identify differentially accessible chromatin regions, selecting the most informative markers using a machine learning algorithm, and targeted sequencing of the selected epigenetic markers using molecular barcodes. Subsequently, a LASSO regression model was constructed and validated. As a proof of concept, the study demonstrates the method’s efficacy in identifying trisomy 21 (Down syndrome), though the underlying principles can be readily adapted to other abnormalities. Complementing its robust performance, the technique offers practical advantages in terms of platform compatibility – the same epigenetic markers can be assessed using either next-generation sequencing or simpler, more cost-efficient methods like digital PCR. With further refinement, the approach could be extended to screen for additional aneuploidies (trisomies 13 and 18) and microdeletion syndromes. Therefore, this approach offers new opportunities for developing cost-effective testing systems suitable for widespread routine clinical implementation, combining high diagnostic accuracy with reduced analysis costs.

The multifactorial etiology of complex diseases involves the interplay of polygenic/oligogenic susceptibility loci and environmental factors. Complex diseases are characterized by pronounced phenotypic variability, genetic heterogeneity, pleiotropy of genetic variants, variable penetrance, and expressivity. Advances in population-wide genomic sequencing have expanded our understanding of the genetic architecture of complex diseases significantly; however, germline variants explain only a fraction of the observed phenotypic variability. The introduction of deep DNA sequencing and single-cell multi-omics analysis has revealed an additional, previously underestimated category of risk factors: somatic mutations that continuously accumulate in cells throughout an individual’s lifespan, giving rise to genetic mosaicism. This review considers the role of somatic mutations in the pathogenesis of complex diseases in the context of their combined contribution with germline determinants to the formation of disease phenotypes. Particular attention is paid to clonal hematopoiesis of indeterminate potential as the best-studied model of somatic mosaicism associated with age-related conditions. It is demonstrated that the interaction of somatic and germline variants occurs within specific tissue contexts through mechanisms of clonal selection, stochastic clonal drift, and epigenetic dysregulation, causing organ dysfunction. Within the concept of somatic mosaicism, this work suggests a selection mechanism alternative to classical oncogenesis. This pathway, defined as “passive clonal dominance”, describes selection through the persistence of clones that gain advantage not via proliferation but through resistance to apoptosis under chronic stress, which may be particularly relevant to post-mitotic tissues such as the heart muscle and nervous tissue. From a practical standpoint, the somatic variants discussed herein are of interest as candidate biomarkers for predictive diagnostics and risk stratification of complex diseases, pending clinical validation. Moreover, they point to pathophysiological pathways that may reveal targets for therapies aimed at modulating clonal composition and preventing disease progression. The paper also discusses prospects for studying somatic mosaicism in the context of complex diseases, including the potential of dynamic lineage tracing technologies for experimental verification of the proposed clonal selection mechanisms, as well as the need to integrate somatic and germline genetic variant data into unified models for individual disease risk assessment.

Mobile genetic elements (MGEs), or transposons, are autonomous DNA sequences capable of moving and proliferating within the genome. Long considered “selfish” or “junk” DNA, MGEs are now recognized as key components involved in genome evolution, the regulation of gene expression, and the pathogenesis of various diseases. In humans, MGEs are divided into two main classes: retrotransposons (Class I), which replicate via an RNA intermediate through a “copy-and-paste” mechanism, and DNA transposons (Class II), which move via a “cut-and-paste” mechanism without an RNA intermediate. According to the Human Genome Project, retrotransposons constitute the majority (approximately 42 %) of the MGE fraction within the human genome. The most abundant are the non-long terminal repeat (non-LTR) retrotransposons, dominated by autonomous LINE-1 elements. Although approximately 500,000 LINE-1 copies are present in the genome, the vast majority are defective, and only a small fraction (<100) retain the capacity for transposition in modern humans. The second most prevalent group (about 10.6 %) within the retrotransposon family is the short interspersed nuclear elements (SINEs), specifically Alu elements, which are non-autonomous and hijack the LINE-1 molecular machinery for their mobilization and integration. MGE activity is a tightly regulated process in somatic tissues. Epigenetic mechanisms, particularly DNA methylation, normally effectively suppress MGE expression and mobility. Disruption of this control is associated with a wide range of pathologies. For instance, hypomethylation and reactivation of retrotransposons, notably LINE-1, have been demonstrated in various cancers, as well as in neurodegenerative and autoimmune diseases. The aim of this review is to provide a systematic analysis of the current understanding of the role of mobile genetic elements, particularly LINE-1, Alu, and HERV retrotransposons, in the development of human reproductive system disorders. This also includes diseases associated with placental pathology, an area that remains insufficiently studied to date, despite a growing body of data.

The sheep was one of the first domesticated animals in Neolithic Southwest Eurasia. The presented study suggests that the domestication of sheep occurred on the Anatolian plateau, to the northwest of the commonly accepted boundaries of the Fertile Crescent, rather than within it. However, many aspects of the domestication process (the specific place, time, and history after domestication) have remained not fully understood. The review examines in detail the complex origin, traces the primary role of the Asian mouflon (Ovis gmelini) as an ancestor, and also discusses controversial aspects of the contribution of other wild Ovis species. It reveals the history of the introduction and migration of sheep in the world, and summarizes the current scientific understanding of the phylogenetic relationships between populations of wild mouflons and domestic sheep (Ovis aries). A multifaceted process of domestication is considered, and the proposed evolutionary mechanisms are discussed, such as the domestication syndrome and hypotheses about thyroid hormones, as well as the human-mediated selection of key phenotypic traits. The article analyzes the results obtained using various genetic markers, including mitochondrial DNA haplogroups. Phylogenetic analysis using mitochondrial DNA has been successfully applied to identify the phylogeographic patterns and divergence times, from the early Neolithic to the Middle Ages, of sheep migration from the domestication center to Asia, Europe, and Africa. Domesticated sheep, having survived and endured extreme climate changes that occurred in the last post-glacial period, became the ancestors of modern local sheep breeds. Starting from the seventh millennium BC, domesticated sheep were brought to the Caucasus, Central Asia, and Europe. The spread of sheep in Asia began from the Middle East to the Mongolian Plateau and the Indian subcontinent, then to the north and southwest of China. In Russia, the territory of which covers a significant part of Eurasia, a unique breed diversity of sheep has been developed, with haplogroup B typical for breeds of the European-type origin (western geographic regions), and haplogroup A of the Asian-type sheep (eastern geographic regions).