Biology subjects

Yurchenko, A. A.

Publications and source records attributed to Yurchenko, A. A..

10 recordsLinked to original sources

bioRxiv2026

MC1R residue 223 is a convergent target for coat-colour lightening in domestic and wild bovids

Whether similar phenotypes evolve through shared substitutions or alternative molecular routes is a central question in evolutionary genomics. Grey-coated taurine cattle provide a powerful system for investigating this question using geographically distinct Podolian and Alpine lineages. We combined whole-genome resequencing data, complementary selection scans (hapFLK, DCMS and FST) and contrasts between grey-coated and non-grey-coated breeds to investigate the molecular evolution of grey coat colour. Selection analyses identified candidate regions associated with Podolian/steppe divergence and a prominent pigmentation-related signal on BTA18 contaning FANCA, MC1R, and SPIRE2. Most grey breeds shared a BTA18 haplotype containing MC1R p.Arg223Trp and additional candidate variants. Tyrolean Grey cattle lacked this predominant haplotype but carried the coding duplication p.Gly220_Arg223dup, together with differentiation near the ASIP regulatory region. Thus, different candidate coding changes affect the same MC1R residue in different cattle lineages. Haplotype comparisons supported independent Podolian and Alpine origins for p.Arg223Trp and p.Gly220_Arg223dup insertion, respectively. Ancient-genome screening yielded no validated evidence of either variant except p.Arg223Trp in medieval cattle. Comparisons across 1,108 mammalian taxa identified independent recurrence of p.Arg223Trp in the white-coated mountain goat, Oreamnos americanus, where the derived allele was fixed in surveyed individuals (JTT-based neutral probability = 0.0043). Our findings support a model in which grey coat colour in cattle evolved through at least two partially distinct molecular routes within interacting pigmentation pathways. More broadly, they identify MC1R residue 223 as a candidate recurrent target of coat-colour lightening and illustrate how domesticated and wild lineages can repeatedly target constrained functional positions during phenotypic evolution.

evolutionary biology↗

bioRxiv2024

Single-cell Transcriptome Profiling of Post-treatment and Treatment-naive Colorectal Cancer: Insights into Putative Mechanisms of Chemoresistance

Drug resistance remains a major clinical challenge in the treatment of colorectal cancer (CRC) with conventional chemotherapy. Analyzing changes within tumor cells and tumor microenvironment (TME) after treatment and in metastases is essential to understanding how resistance develops. In this study, we analyzed scRNA-seq data from 56 CRCs including treatment-naive tumors and tumors treated with standard chemotherapy with the known response status (18 responders and 6 progressors). In our cohort, primary left-sided CRCs were associated with metastatic potential mesenchymal phenotype and with depleted B cells. In the post-treatment CRC, there was a high prevalence of dendritic cells (DC) in the TME in the response group. The DC-derived signature was associated with better survival in a large CRC cohort from the TCGA. In progressors there was an enrichment of pericyte-like fibroblasts, which appeared to be associated with poor survival in a CRC-TCGA cohort. Progressors also showed elevated fractions of exhausted CD8+ T memory cells suggesting a pro-inflammatory TME. In tumor cells of progressors group, we identified specific expression of chemo-protective markers MTRNR2L1 and CDX1; and their co-expression with stemness-related immune-checkpoint CD24. In summary, scRNA-seq provides a valuable information for the discovery of prognostic markers, and reveals distinct features potentially underlying response to chemotherapy or disease progression in CRC.

cancer biology↗

bioRxiv2024

Discovery and characterization of chromosomal inversions in the arboviral vector mosquito Aedes aegypti

Chromosomal inversions play a fundamental role in evolution and have been shown to regulate epidemiologically important traits in malaria mosquitoes. However, they have never been characterized in Aedes aegypti, the major vector of arboviruses, because of the poor structure of its polytene chromosomes. In this study, we applied a Hi-C proximity ligation approach to identify chromosomal inversions in 25 strains of Ae. aegypti, acquired from its worldwide distribution, as well as in one strain of Ae. mascarensis. The study identified 21 multi-megabase inversions with uneven distributions along the three chromosomes. All chromosomal inversions, including one specific for Ae. mascarensis, were polymorphic. Nevertheless, geographic origin separated the strains into two clusters carrying African and non-African inversions suggesting their potential association with Ae. aegypti subspecies. Some of the inversions colocalized with chemoreceptor genes and quantitative trait loci associated with pathogen infection, implicating the potential role of inversions in host choice and disease transmission.

evolutionary biology↗

bioRxiv2022

Patterns of genetic differentiation imply distinct evolutionary histories of the sibling mosquito species Anopheles messeae and Anopheles daciae in Eurasia

Detailed knowledge of phylogeography is important for control of mosquito species involved in transmission of human infectious diseases. Anopheles messeae is a geographically widespread and genetically diverse dominant vector of malaria in Eurasia. A closely related sibling species, An. daciae, was distinguished from An. messeae based on a few nucleotide differences in its ribosomal DNA. However, the mechanisms of speciation and their evolutionary histories are poorly understood. Here, we performed a large-scale population genetics analysis of 3694 mosquitos from Eurasia to understand the species divergence, diversity, and population structure using the Internal Transcribed Spacer 2 of ribosomal DNA for species identification and frequencies of 11 polymorphic chromosomal inversions as genetic markers. The study revealed striking differences in the geographical distribution of the sibling species. The largest genetic differences between An. messeae and An. daciae were detected in the X sex chromosome suggesting that this chromosome plays a role in speciation. The frequencies of autosomal inversions differed significantly between the species, strongly supporting a restricted gene flow. The clinal variability of some inversion frequencies was revealed in both species implicating their possible involvement in climate adaptations. Statistical analysis of inversion polymorphism clearly distinguished two clusters associated with the two species and demonstrated much higher genetic diversity within An. messeae. Overall, the frequencies of hybrids in all locations were extremely low with the exception of several southeastern populations, where putative hybrids were abundant. Thus, the pattern of genetic differentiation implies dramatic differences in geographic distribution, population structure, and evolutionary histories of the sibling species An. messeae and An. daciae.

evolutionary biology↗

bioRxiv2022

Analysis of Skin Cancers from Xeroderma Pigmentosum Patients Reveals Heterogeneous UV-Induced Mutational Profiles Shaped by DNA Repair

Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis (TLS) DNA polymerase {eta} (V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyzed 38 skin cancer genomes from five XP groups. We found that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate. Mutational profile in XP-V tumors and experiments with POLH-KO cell line revealed the role of polymerase {eta} in the error-free bypass of (i) rare TpG and TpA DNA lesions, (ii) 3 nucleotides in pyrimidine dimers, and (iii) TpT photodimers. Our study unravels the genetic basis of skin cancer risk in XP and provides insights into the mechanisms reducing UV-induced mutagenesis in the general population.

cancer biology↗

bioRxiv2022

Phylogenomics revealed migration routes and adaptive radiation timing of Holarctic malaria vectors of the Maculipennis group

BackgroundUnderstanding the evolutionary relationships between closely related taxa is important for mosquitoes that transmit human diseases. Six out of 41 dominant malaria vectors in the world belong to the Maculipennis group, which is subdivided into two North American subgroups (Freeborni and Quadrimaculatus), and one Eurasian (Maculipennis) subgroup. Although previous studies considered the Nearctic subgroups as ancestral, details about their relationship with the Palearctic subgroup, and their migration times and routes from North America to Eurasia remain controversial. The Eurasian species An. beklemishevi is currently included in the North American Quadrimaculatus subgroup adding to the uncertainties in mosquito systematics. ResultsTo reconstruct historic relationships between the North American and Eurasian mosquitoes, we conducted a phylogenomic analysis of 11 Palearctic and 2 Nearctic species based on 1271 orthologous genes using their transcriptomic or genomic sequences. The analysis indicated that the Palearctic species An. beklemishevi clusters together with other Eurasian species and represents a basal lineage among them. Also, An. beklemishevi is related more closely to An. freeborni, which inhabits the Western United States, rather than to An. quadrimaculatus, a species from the Eastern United States. The time-calibrated tree suggests a migration of mosquitoes in the Maculipennis group from North America to Eurasia about 20-25 million years ago through the Bering Land Bridge. A Hybridcheck analysis demonstrated highly significant signatures of introgression events between allopatric species An. labranchiae and An. beklemishevi. The analysis also identified ancestral introgression events between An. sacharovi and its Nearctic relative An. freeborni despite their current geographic isolation. ConclusionsOur phylogenomic analyses reveal migration routes and adaptive radiation timing of Holarctic malaria vectors and strongly support inclusion of An. beklemishevi into the Maculipennis subgroup. The vectorial capacity and the ability to diapause during winter evolved multiple times in Maculipennis evolution. Detailed knowledge of the evolutionary history in the Maculipennis subgroup will help us better understand the current and future patterns of malaria transmission in Eurasia.

evolutionary biology↗

bioRxiv2020

XPC deficiency increases risk of hematologic malignancies through mutator phenotype and characteristic mutational signature

Recent studies demonstrated a dramatically increased risk of leukemia in patients with a rare genetic disorder, Xeroderma Pigmentosum group C (XP-C), characterized by constitutive deficiency of global genome nucleotide excision repair (GG-NER). However, the genetic mechanisms of non-skin cancers in XP-C patients remain unexplored. In this study, we analyzed a unique collection of internal XP-C tumor genomes including 6 leukemias and 2 sarcomas. We observed an average of 25-fold increase of mutation rates in XP-C vs. sporadic leukemia which we presume leads to its elevated incidence and early appearance. In all XP-C tumors predominant mutational process is characterized by a distinct mutational signature, highlighting a specific mutational pattern in the context of GG-NER deficiency. We observed a strong mutational asymmetry with respect to transcription and the direction of replication in XP-C tumors suggesting association of mutagenesis with bulky purine DNA lesions of probably endogenous origin. These findings suggest existence of a balance between formation and repair of bulky DNA lesions by GG-NER in human body cells which is disrupted in XP-C patients leading to internal cancers.

cancer biology↗

bioRxiv2020

Demographic history, cold adaptation, and recent NRAP recurrent convergent evolution at amino acid residue 100 in the world northernmost cattle from Russia

Native cattle breeds represent an important cultural heritage. They are a reservoir of genetic variation useful for properly responding to agriculture needs in light of ongoing climate changes. Evolutionary processes that occur in response to extreme environmental conditions could also be better understood using adapted local populations. Herein, different evolutionary histories for two of the world northernmost native cattle breeds from Russia were investigated. They highlighted Kholmogory as a typical taurine cattle, while Yakut cattle separated from European taurines ~5,000 years ago and contain numerous ancestral and some novel genetic variants allowing their adaptation to harsh conditions of living above the Polar Circle. Scans for selection signatures pointed to several common gene pathways related to adaptation to harsh climates in both breeds. But genes affected by selection from these pathways were mostly different. A Yakut cattle breed-specific missense mutation, H100Q, in a highly conserved NRAP gene, represents a unique example of a young amino acid residue convergent change shared with at least 16 species of hibernating/cold-adapted mammals from nine distinct phylogenetic orders. This suggests a convergent evolution event along the mammalian phylogenetic tree and fast fixation in a single isolated cattle population exposed to a harsh climate.

genomics↗

bioRxiv2019

Genomic differentiation and intercontinental population structure of mosquito vectors Culex pipiens pipiens and Culex pipiens molestus

Understanding the population structure and mechanisms of taxa diversification is important for organisms responsible for the transmission of human diseases. Two vectors of West Nile virus, Culex pipiens pipiens and Cx. p. molestus, exhibit epidemiologically important behavioral and physiological differences, but the whole-genome divergence between them was unexplored. In this study, we re-sequenced and compared the whole genomes of 40 individual mosquitoes from four locations in Eurasia and North America: the Republic of Belarus, the Kyrgyz Republic, and the United States of America. Principal Component, ADMIXTURE, and neighbor joining analyses of the nuclear genomes identified two intercontinental, monophyletic clusters of Cx. p. pipiens and Cx. p. molestus. The third cluster, having a polyphyletic origin, was formed by Cx. p. pipiens and Cx. quinquefasciatus from the USA. The level of genomic differentiation between the subspecies was uniform along chromosomes. The ADMIXTURE analysis determined signatures of admixture in all Cx. p. pipens populations but not in Cx. p. molestus populations. Comparison of mitochondrial genomes among the specimens showed a paraphyletic origin of the major haplogroups between the subspecies but a monophyletic structure between the continents. Thus, our study identified that Cx. p. molestus and Cx. p. pipiens represent different evolutionary units with monophyletic origin that have undergone incipient ecological speciation.

genomics↗

bioRxiv2019

Chromosome-level assembly of the common lizard (Zootoca vivipara) genome

Squamate reptiles exhibit high variation in their traits and geographical distribution and are therefore fascinating taxa for evolutionary and ecological research. However, high-quality genomic recourses are very limited for this group of species, which inhibits some research efforts. To address this gap, we assembled a high-quality genome of the common lizard Zootoca vivipara (Lacertidae) using a combination of high coverage Illumina (shotgun and mate-pair) and PacBio sequence data, with RNAseq data and genetic linkage maps. The 1.46 Gbp genome assembly has scaffold N50 of 11.52 Mbp with N50 contig size of 220.4 Kbp and only 2.96% gaps. A BUSCO analysis indicates that 97.7% of the single-copy Tetrapoda orthologs were recovered in the assembly. In total 19,829 gene models were annotated in the genome using a combination of three ab initio and homology-based methods. To improve the chromosome-level assembly, we generated a high-density linkage map from wild-caught families and developed a novel analytical pipeline to accommodate multiple paternity and unknown father genotypes. We successfully anchored and oriented almost 90% of the genome on 19 linkage groups. This annotated and oriented chromosome-level reference genome represents a valuable resource to facilitate evolutionary studies in squamate reptiles.

genomics↗