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Birth-and-death evolution of ribonuclease 9 genes in Cetartiodactyla

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Science China(Life Sciences) 2023年第5期66卷 1170-1182页

作者： Datian Lang Xiaoping Wang Chunbing Liu Weihang Geng david m.irwin Shanyuan Chen Chunqing Li Li Yu Heng Xiao School of Life Sciences Yunnan UniversityKunming 650500China School of Ecology and Environmental Science Yunnan UniversityKunming 650091China State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan Yunnan UniversityKunming 650091China Biodiversity Research Center of Wumeng mountain Department of Agronomy and Life ScienceZhaotong UniversityZhaotong 657000China Department of Laboratory medicine and Pathobiology University of TorontoTorontoOntario M5S 1A8Canada

RNase9 plays a reproductive function and has been recognized as an important member of the ribonuclease(RNase)A superfamily,a gene family that is widely used as a model for molecular evolutionary studies.Here,we identified 178 RNase9 genes from 95 Cetartiodactyla species that represent all four lineages and 21 families of this clade.Unexpectedly,RNase9experienced an evolutionary scenario of“birth and death”in Ruminantia,and expression analyses showed that duplicated RNase9A and RNase9B genes are expressed in reproductive tissues(epididymis,vas deferens or prostate).This expression pattern combined with the estimate that these genes duplicated during the middle Eocene,a time when Ruminantia become a successful lineage,suggests that the RNase9 gene duplication might have been advantageous for promoting sperm motility and male fertility as an adaptation to climate seasonality changes of this period.In contrast,all RNase9 genes were lost in the Cetacean lineage,which might be associated with their high levels of prostatic lesions and lower reproductive rates as adaptations to a fully aquatic environment and a balance to the demands of ocean resources.This study reveals a complex and intriguing evolutionary history and functional divergence for RNase9 in Cetartiodactyla,providing new insights into the evolution of the RNaseA superfamily and molecular mechanisms for organismal adaptations to the environment.

关键词： RNase9 gene duplication gene loss Cetartiodactyla

The role of N-glycosylation in cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1098-1110页

作者： Yu Lin david m.Lubman Department of Surgery University of Michigan Medical CenterAnn ArborMI 48109USA

Despite advances in understanding the development and progression of cancer in recent years,there remains a lack of comprehensive characterization of the cancer glycoproteome.Glycoproteins play an important role in medicine and are involved in various human disease conditions including cancer.Glycan-moieties participate in fundamental cancer processes like cell signaling,invasion,angiogenesis,and metastasis.Aberrant N-glycosylation significantly impacts cancer processes and targeted therapies in clinic.Therefore,understanding N-glycosylation in a tumor is essential for comprehending disease progression and discovering anti-cancer targets and biomarkers for therapy monitoring and diagnosis.This review presents the fundamental process of protein N-glycosylation and summarizes glycosylation changes in tumor cells,including increased terminal sialylation,N-glycan branching,and corefucosylation.Also,the role of N-glycosylation in tumor signaling pathways,migration,and metabolism are discussed.Glycoproteins and glycopeptides as potential biomarkers for early detection of cancer based on site specificity have been introduced.Collectively,understanding and exploring the cancer glycoproteome,along with its role in medicine,implication in cancer and other human diseases,highlights the significance of N-glycosylation in tumor processes,necessitating further research for potential anticancer targets and biomarkers.

关键词： N-Glycosylated proteins Cancer signaling Cancer angiogenesis Cancer metabolism Cancer biomarkers

Genome-wide identification of functional enhancers and their potential roles in pig breeding

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Journal of Animal Science and Biotechnology 2022年第6期13卷 1690-1702页

作者： Yinqiao Wu Yuedong Zhang Hang Liu Yun Gao Yuyan Liu Ling Chen Lu Liu david m.irwin Chunhui Hou Zhongyin Zhou Yaping Zhang State Key Laboratory of Genetic Resources and Evolution and Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650223YunnanChina Kunming College of Life Science University of Chinese Academy of SciencesKunming 650204YunnanChina State Key Laboratory for Conservation and Utilization of Bio-resource in Yunnan Yunnan UniversityKunming 650091YunnanChina School of Life Science Yunnan UniversityKunming 650091YunnanChina Institute of Physical Science and Information Technology Anhui UniversityHefei 230601AnhuiChina Department of Laboratory medicine and Pathobiology University of TorontoTorontoCanada Department of Biology School of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223YunnanChina

Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,development and disease.Genome-wide quantification of functional enhancers in the pig is needed.Results:We performed self-transcribing active regulatory region sequencing(STARR-seq)in the porcine kidney epithelial PK15 and testicular ST cell lines,and reliably identified 2576 functional enhancers.most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes.Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3,which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones.This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages.Additionally,the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers.Conclusions:In summary,we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.

关键词： Breeding Functional enhancers Pig STARR-seq

Unveiling the functional and evolutionary landscape of RNA editing in chicken using genomics and transcriptomics

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Zoological Research 2022年第6期43卷 1011-1022页

作者： Yun-mei Wang Ling-Qun Ye ming-Shan Wang Jin-Jin Zhang Saber Khederzadeh david m irwin Xiao-Die Ren Ya-Ping Zhang Dong-Dong Wu State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan650223China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan650223China Kunming College of Life Science University of the Chinese Academy of SciencesKunmingYunnan650223China KIZ-CUHK Joint Laboratory of Bioresources and molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650201China Department of Ecology and Evolutionary Biology Howard Hughes Medical InstituteUniversity of California Santa CruzSanta CruzCA 95064USA Department of Laboratory medicine and Pathobiology University of TorontoTorontoOntario M5S 1A8Canada Kunming Natural History museum of Zoology Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China

The evolutionary and functional features of RNA editing are well studied in mammals,cephalopods,and insects,but not in birds.Here,we integrated transcriptomic and whole-genomic analyses to exhaustively characterize the expansive repertoire of adenosine-to-inosine(A-to-I)RNA editing sites(RESs)in the chicken.In addition,we investigated the evolutionary status of the chicken editome as a potential mechanism of domestication.We detected the lowest editing level in the liver of chickens,compared to muscles in humans,and found higher editing activity and specificity in the brain than in non-neural tissues,consistent with the brain’s functional complexity.To a certain extent,specific editing activity may account for the specific functions of tissues.Our results also revealed that sequences critical to RES secondary structures remained conserved within avian evolution.Furthermore,the RNA editome was shaped by purifying selection during chicken domestication and most RESs may have served as a selection pool for a few functional RESs involved in chicken domestication,including evolution of nervous and immune systems.Regulation of RNA editing in chickens by adenosine deaminase acting on RNA(ADAR)enzymes may be affected by non-ADAR factors whose expression levels changed widely after ADAR knockdown.Collectively,we provide comprehensive lists of candidate RESs and non-ADAR-editing regulators in the chicken,thus contributing to our current understanding of the functions and evolution of RNA editing in animals.

关键词： RNA editing Transcriptomics Population genomics Domestication Evolution Chicken

Genomic organization and evolution of ruminant lysozyme c genes

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Zoological Research 2015年第1期36卷 1-17页

作者： david m.irwin Department of Laboratory medicine and Pathobiology University of Toronto Banting and Best Diabetes Centre University of Toronto

Ruminant stomach lysozyme is a long established model of adaptive gene evolution. Evolution of stomach lysozyme function required changes in the site of expression of the lysozyme c gene and changes in the enzymatic properties of the enzyme. In ruminant mammals, these changes were associated with a change in the size of the lysozyme c gene family. The recent release of near complete genome sequences from several ruminant species allows a more complete examination of the evolution and diversification of the lysozyme c gene family. Here we characterize the size of the lysozyme c gene family in extant ruminants and demonstrate that their pecoran ruminant ancestor had a family of at least 10 lysozyme c genes, which included at least two pseudogenes. Evolutionary analysis of the ruminant lysozyme c gene sequences demonstrate that each of the four exons of the lysozyme c gene has a unique evolutionary history, indicating that they participated independently in concerted evolution. These analyses also show that episodic changes in the evolutionary constraints on the protein sequences occurred, with lysozyme c genes expressed in the abomasum of the stomach of extant ruminant species showing the greatest levels of selective constraints.

关键词： lysozyme ruminant evolutionary Genomic extant stomach genomic constraints Ailuropoda duplication

mitochondrial recruitment in myelin:an anchor for myelin dynamics and plasticity?

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Neural Regeneration Research 2024年第7期19卷 1401-1402页

作者： Jean-david m.Gothié Timothy E.Kennedy Department of Neurology and Neurosurgery Montreal Neurological InstituteMcGill UniversityMontrealQCCanada

Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by oligodendrocytes.myelin is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered sheath.myelin is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.

关键词： plasticity insulation dynamics

Establishment of an optimized CTC detection model consisting of EpCAm,mUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics

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Chinese Journal of Cancer Research 2022年第2期34卷 95-108页

作者： Tongxia Wang Yan Gao Xi Wang Junrui Tian Yuan Li Bo Yu Cuiyu Huang Hui Li Huamao Liang david m.irwin Huanran Tan Hongyan Guo Department of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Department of Pharmacology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Laboratory medicine and Pathobiology University of TorontoToronto M5S1A8Canada

Objective:Emerging studies have demonstrated the promising clinical value of circulating tumor cells(CTCs)for diagnosis,disease assessment,treatment monitoring and prognosis in epithelial ovarian cancer.However,the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.methods:We enrolled 160 patients with epithelial ovarian cancer as the experimental group,and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group.We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens(EpCAm and mUC1),and used multiple reverse transcription-polymerase chain reaction(RT-PCR)detecting three markers(EpCAm,mUC1 and WT1)for quantification.And then we used a binary logistic regression analysis and focused on EpCAm,mUC1 and WT1 to establish an optimized CTC detection model.Results:The sensitivity and specificity of the optimized model is 79.4%and 92.2%,respectively.The specificity of the CTC detection model is significantly higher than CA125(92.2%vs.82.2%,P=0.044),and the detection rate of CTCs was higher than the positive rate of CA125(74.5%vs.58.2%,P=0.069)in early-stage patients(stage I and II).The detection rate of CTCs was significantly higher in patients with ascitic volume≥500 mL,suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy(Pmo-resistant patients(26.3%vs.11.9%;26.4%vs.13.4%,Pmedian progression-free survival time for CTC;patients trended to be longer than CTC;patients,and overall survival was shorter in CTC;patients(P=0.043).Conclusions:Our study presents an optimized detection model for CTCs,which consists of the expression levels of three markers(EpCAm,mUC1 and WT1).In comparison with CA125,our model has high specificity and demonstrates better diagnostic values,especially for early-stage ovarian cancer.Detection of

关键词： Circulating tumor cells epithelial ovarian cancer optimized detection model diagnosis and prognosis

Late Ordovician mass Extinction: Earth, fire and ice

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National Science Review 2024年第1期11卷 51-65页

作者： david A.T.Harper Palaeoecosystems Group Department of Earth SciencesDurham University

The Late Ordovician mass Extinction was the earliest of the ‘big’ five extinction events and the earliest to affect the trajectory of metazoan life. Two phases have been identified near the start of the Hirnantian period and in the middle. It was a massive taxonomic extinction, a weak phylogenetic extinction and a relatively benign ecological extinction. A rapid cooling, triggering a major ice age that reduced the temperature of surface waters, prompted a drop in sea level of some 100 m and introduced toxic bottom waters onto the shelves. These symptoms of more fundamental planetary processes have been associated with a range of factors with an underlying driver identified as volcanicity. Volcanic eruptions, and other products, may have extended back in time to at least the Sandbian and early Katian, suggesting the extinctions were more protracted and influential than hitherto documented.

关键词： Ordovician LOmE paleoecology palaeobiogeography biotas

multi‑omics integration identifies regulatory factors underlying bovine subclinical mastitis

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Journal of Animal Science and Biotechnology 2024年第3期15卷 987-1007页

作者： mengqi Wang Naisu Yang mario Laterriere david Gagne Faith Omonijo Eveline m.Ibeagha‑Awemu Agriculture and Agri‑Food Canada Sherbrooke Research and Development CentreSherbrookeQCCanada Department of Animal Science Universite LavalQuebec CityQCCanada Quebec Research and Development Centre Agriculture and Agri-Food CanadaQuebec CityQCCanada

Background mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry.multi-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease pathogenesis.Therefore,this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data(mRNA and lncRNA),small RNA sequencing data(miRNA)and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes.Results Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis,provided further insights into subclin-ical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis.The abundant genomic and epigenomic signatures with sig-nificant alterations related to subclinical mastitis were observed,including 30,846,2552,1276 and 57 differential methylation haplotype blocks(dmHBs),differentially expressed genes(DEGs),lncRNAs(DELs)and miRNAs(DEms),respectively.Next,5 factors presenting the principal variation of differential multi-omics signatures were identified.The important roles of Factor 1(DEG,DEm and DEL)and Factor 2(dmHB and DEm),in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed.Each of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical mastitis.Also,networks of impor-tant functional gene sets with the involvement of multi-omics signatures were demonstrated,which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastiti

关键词： Candidate discriminant multi-omics signature Gene Long non-coding RNA methylation haplotype block microRNA multi-omics integration Natural killer cell mediated cytotoxicity pathway Staphylococcus aureus infection pathway