White Shark Genome Reveals Ancient Elasmobranch Adaptations Associated with Wound Healing and the Maintenance of Genome Stability

The white shark (Carcharodon carcharias; Chondrichthyes, Elasmobranchii) is one of the most publicly recognized marine animals. Here we report the genome sequence of the white shark and comparative evolutionary genomic analyses to the chondrichthyans, whale shark (Elasmobranchii) and elephant shark (Holocephali), as well as various vertebrates. The 4.63-Gbp white shark genome contains 24,520 predicted genes, and has a repeat content of 58.5%. We provide evidence for a history of positive selection and gene-content enrichments regarding important genome stability-related genes and functional categories, particularly so for the two elasmobranchs. We hypothesize that the molecular adaptive emphasis on genome stability in white and whale sharks may reflect the combined selective pressure of large genome sizes, high repeat content, high long-interspersed element retrotransposon representation, large body size, and long lifespans, represented across these two species. Molecular adaptation for wound healing was also evident, with positive selection in key genes involved in the wound-healing process, as well as Gene Ontology enrichments in fundamental wound-healing pathways. Sharks, particularly apex predators such as the white shark, are believed to have an acute sense of smell. However, we found very few olfactory receptor genes, very few trace amine-associated receptors, and extremely low numbers of G protein-coupled receptors. We did however, identify 13 copies of vomeronasal type 2 (V2R) genes in white shark and 10 in whale shark; this, combined with the over 30 V2Rs reported previously for elephant shark, suggests this gene family may underlie the keen odorant reception of chondrichthyans

Draft de novo Genome Assembly of the Elusive Jaguarundi, Puma yagouaroundi

The Puma lineage within the family Felidae consists of 3 species that last shared a common ancestor around 4.9 million years ago. Whole-genome sequences of 2 species from the lineage were previously reported: the cheetah (Acinonyx jubatus) and the mountain lion (Puma concolor). The present report describes a whole-genome assembly of the remaining species, the jaguarundi (Puma yagouaroundi). We sequenced the genome of a male jaguarundi with 10X Genomics linked reads and assembled the whole-genome sequence. The assembled genome contains a series of scaffolds that reach the length of chromosome arms and is similar in scaffold contiguity to the genome assemblies of cheetah and puma, with a contig N50 = 100.2 kbp and a scaffold N50 = 49.27 Mbp. We assessed the assembled sequence of the jaguarundi genome using BUSCO, aligned reads of the sequenced individual and another published female jaguarundi to the assembled genome, annotated protein-coding genes, repeats, genomic variants and their effects with respect to the protein-coding genes, and analyzed differences of the 2 jaguarundis from the reference mitochondrial genome. The jaguarundi genome assembly and its annotation were compared in quality, variants, and features to the previously reported genome assemblies of puma and cheetah. Computational analyzes used in the study were implemented in transparent and reproducible way to allow their further reuse and modification. </p

Analytical “Bake-Off” of Whole Genome Sequencing Quality for the Genome Russia Project Using a Small Cohort for Autoimmune Hepatitis

A comparative analysis of whole genome sequencing (WGS) and genotype calling was initiated for ten human genome samples sequenced by St. Petersburg State University Peterhof Sequencing Center and by three commercial sequencing centers outside of Russia. The sequence quality, efficiency of DNA variant and genotype calling were compared with each other and with DNA microarrays for each of ten study subjects. We assessed calling of SNPs, indels, copy number variation, and the speed of WGS throughput promised. Twenty separate QC analyses showed high similarities among the sequence quality and called genotypes. The ten genomes tested by the centers included eight American patients afflicted with autoimmune hepatitis (AIH), plus one case’s unaffected parents, in a prelude to discovering genetic influences in this rare disease of unknown etiology. The detailed internal replication and parallel analyses allowed the observation of two of eight AIH cases carrying a rare allele genotype for a previously described AIH-associated gene (FTCD), plus multiple occurrences of known HLA-DRB1 alleles associated with AIH (HLA-DRB1-03:01:01, 13:01:01 and 7:01:01). We also list putative SNVs in other genes as suggestive in AIH influence

Genome-wide sequence analyses of ethnic populations across Russia

The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation. Here we report the characterization of genome-wide variation of 264 healthy adults, including 60 newly sequenced samples. People of Russia carry known and novel genetic variants of adaptive, clinical and functional consequence that in many cases show allele frequency divergence from neighboring populations. Population genetics analyses revealed six phylogeographic partitions among indigenous ethnicities corresponding to their geographic locales. This study presents a characterization of population-specific genomic variation in Russia with results important for medical genetics and for understanding the dynamic population history of the world's largest country

Влияние дексаметазона на экспрессию и содержание гликозилированных компонентов в ткани головного мозга мышей

Introduction. Glucocorticoids are actively used in the treatment of various diseases, however their long-term use leads to numerous negative side-effects, the molecular mechanisms of which remain poorly understood.Aim. Study of the short-term (1–10 days) effects of various doses of dexamethasone (Dex) (0,1–10 mg/kg) on the expression of the glucocorticoid receptor (GR, Nr3c1), core proteins of main proteoglycans and heparan sulfate metabolism-involved genes, as well as the content of carbohydrate macromolecules of glycosaminoglycans in the brain tissue of experimental animals.Materials and methods. In the study, C57Bl/6 mice were used. The expression of GR, proteoglycan core proteins and heparan sulfate metabolism-involved genes was determined by real-time polymerase chain reaction with reverse transcription. The content and localization of GR protein molecule were studied by Western blot and immunohistochemical analysis, and the glycosaminoglycan content was determined by dot-blot analysis and Alcian Blue staining.Results. It was shown that a single Dex administration leads to fast (1–3 days) short-term activation of GR expression (+1.5 times, p &lt;0.05), proteoglycan’s genes (syndecan-3, Sdc3; perlecan, Hspg2; phosphacan, Ptprz1; neurocan, Ncan; +2–3-fold; p &lt;0.05) and heparan sulfate-metabolism-involved genes (Ndst1, Glce, Hs2st1, Hs6st1, Sulf1 / 2; +1.5–2-fold; p &lt;0.05) in the mouse brain, with a return to control values by 7–10 days after Dex administration. At the same time, the effect of Dex on carbohydrate macromolecules of glycosaminoglycans was more delayed and stable, increasing the content of low-sulfated glycosaminoglycans in the brain tissue in a dose-dependent manner starting from day 1 after Dex administration. Highly-sulfated glycosaminoglycans showed more delayed response to Dex administration, and an increase in their content was observed only at higher doses (2.5 and 10 mg/kg) and only on 7–10 days after its administration, apparently, mainly due to an increase in heparan sulfate content.Conclusion. In general, the effect of a single injection of Dex on the transcriptional activity of GR, proteoglycan core proteins and heparan sulfate metabolism-involved genes were short-termed, and the genes expression quickly returned to the normal levels. However, even a single use of Dex significantly increased the content of total as well as highly sulfated glycosaminoglycans in the mouse brain tissue, which can lead to the changes in the composition and structure of the brain tissue, as well as its functional characteristics.Введение. Глюкокортикоиды активно используются при лечении различных заболеваний, однако их длительное применение приводит ко множеству побочных эффектов, молекулярные механизмы развития которых остаются недостаточно изученными.Цель исследования – изучение краткосрочного (1–10 сут) влияния различных доз дексаметазона (Dex) (0,1–10 мг/кг) на экспрессию глюкокортикоидного рецептора (GR, Nr3c1), коровых белков основных протеогликанов и ферментов биосинтеза углеводных цепей гепарансульфата, а также содержание углеводных макромолекул гликозаминогликанов в ткани головного мозга экспериментальных животных.Материалы и методы. В исследовании использовали мышей линии C57Bl/6. Экспрессию GR, коровых белков протеогликанов и генов, кодирующих ферменты биосинтеза гепарансульфата, определяли с помощью полимеразной цепной реакции с обратной транскрипцией в реальном времени. Содержание и локализация белковой молекулы GR были изучены методами Вестерн-блоттинга и иммуногистохимического анализа, а содержание гликозаминогликанов – с помощью дот-блот анализа и окраски альциановым синим.Результаты. Было показано, что однократное введение Dex приводило к быстрой (на 1–3-и сутки) кратковременной активации экспрессии GR (+1,5 раза; p &lt;0,05) некоторых генов коровых белков протеогликанов (синдекан-3, Sdc3; перлекан, Hspg2; фосфакан, Ptprz1; нейрокан, Ncan; +2–3 раза; p &lt;0,05) и генов ферментов биосинтеза гепарансульфатов (Ndst1, Glce, Hs2st1, Hs6st1, Sulf1 / 2; +1,5–2 раза; p &lt;0,05) в мозге мышей с возвращением к контрольным показателям к 7–10-м суткам после введения Dex. При этом влияние данного препарата на углеводные макромолекулы гликозаминогликанов имело более отсроченный и стабильный характер, дозозависимо увеличивая содержание общих гликозаминогликанов в ткани мозга, начиная с 1-х суток после введения Dex. Высокосульфатированные гликозаминогликаны демонстрировали более медленный ответ на введение препарата, повышение их содержания наблюдалось только при более высоких дозах (2,5 и 10 мг/кг) и только на 7–10-е сутки после его введения в основном за счет повышения содержания гепарансульфата.Заключение. Влияние однократного применения Dex на транскрипционную активность GR, протеогликанов и ферментов биосинтеза гепарансульфата носит кратковременный характер, и экспрессия генов быстро возвращается к нормальному уровню. Однако даже однократное применение Dex значительно повышает содержание общих и высокосульфатированных гликозаминогликанов в ткани головного мозга мышей, что может привести к изменению состава и структуры ткани головного мозга, а также его функциональных характеристик