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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

Motilin and ghrelin gene experienced episodic evolution during primitive placental mammal evolution

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Science China(Life Sciences) 2010年第6期53卷 677-682页

作者： IRWIN M. David Departments of Laboratory Medicine and Pathobiology and the banting and best diabetes centre University of Toronto

Motilin and ghrelin,members of a structure-function-related hormone family,play important roles in gastrointestinal function,regulation of energy homeostasis and growth hormone *** observed episodic evolution in both of their prehormone gene sequences during primitive placental mammal evolution,during which most of the nonsynonymous changes result in radical *** note,a functional obestatin hormone might have only originated after this episodic evolution *** in placental mammal evolution,a series of biology complexities *** the same time the motilin and ghrelin prehormone genes,which play important roles in several of these processes,experienced episodic evolution with dramatic changes in their coding *** observations suggest that some of the lineage-specific physiological adaptations are due to episodic evolution of the motilin and ghrelin genes.

关键词： motilin ghrelin episodic evolution

THE GROWTH OF SINGLE CRYSTALS OF （L-ARGININE）B0 BOVINE INSULIN AND THEIR PRELIMINARY X-RAY CRYSTALLOGRAPHIC ANALYSIS

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Science in China,Ser.B 1984年第5期27卷 478-481页

作者：万柱礼梁栋材叶长菁 Institute of Biophysics Academia Sinica Beijing The banting and best Department of Medical Research University of Toronto Canada

The crystals of （L-Arg）B0 bovine insulin large enough for X-ray structure analysis havebeen grown by vapour diffusion in a buffer containing citrate, acetone and zinc *** X-ray diffraction of the crystals extends to 3.0 A spacing. The crystals belong tothe trigonal system with unit cell dimension of a=b=81.82A, c=35.05A, α=β=90°, γ=120°,space group R3. There are two insulin molecules in the crystallographic asymmetric unit.

关键词： L-ARGININE THE GROWTH OF SINGLE CRYSTALS OF BOVINE INSULIN AND THEIR PRELIMINARY X-RAY CRYSTALLOGRAPHIC ANALYSIS B0

Rapid Evolution of the Mammalian HILS1 Gene and the Nuclear Condensation Process during Mammalian Spermiogenesis

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Journal of Genetics and Genomics 2013年第1期40卷 55-59页

作者： Yanhua Su Dongdong Wu Weiping Zhou David M.Irwin Yaping Zhang Laboratory for Conservation and Utilization of Bio-Resources & Key Laboratory for Microbial Resources of the Ministry of Education Yunnan University State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences Department of Laboratory Medicine and Pathobiology University of Toronto banting and best diabetes centre University of Toronto

Many genes associated with reproduction show rapid evolution across diverse animal groups, a result commonly due to adaptive evolution driven by positive selection （Swanson and Vacquier, 2002）. Different theories have been proposed to explain the elevated rates of evolution （Swanson and Vacquier, 2002）, including sperm competition, where sperm compete to fertilize eggs leading to the proteins in the sper- matozoa adaptively evolving to increase their ability to fertilize eggs; sexual conflict, where the egg experiences a loss of fitness when sperm are too abundant; sexual selection, where eggs bind sperm carrying adaptive alleles （Palumbi, 1999）; and cryptic female choice （reviewed in Swanson and Vacquier, 2002）.

关键词： Rapid Evolution of the Mammalian HILS1 Gene and the Nuclear Condensation Process during Mammalian Spermiogenesis HILS gene

Gene duplication plays a major role in gene co-option: Studies into the evolution of the motilin/ghrelin family and their receptors

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Chinese Science Bulletin 2011年第25期56卷 2690-2697页

作者： HE Jing Irwin M. DAVID ZHANG YaPing State Key Laboratory of Genetic Resource and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China Department of Laboratory Medicine and Pathobiology and banting and best diabetes centre University of Toronto Toronto M5S1A1 Canada Laboratory for Conservation and Utilization ofBioresource Yunnan University Kunming 650091 China

Extant genes can be modified, or 'tinkered with', to provide new roles or new characteristics of these genes. At the genetic level, this often involves gene duplication and specialization of the resulting genes into particular functions. We investigate how ligand-receptor partnerships evolve after gene duplication. While significant work has been conducted in this area, the examination of additional models should help us better understand the proposed models and potentially reveal novel evolutionary patterns and dynamics. We use bioinformatics, comparative genomics and phylogenetic analyses to show that preproghrelin and prepromotilin descended from a common ancestor and that a gene duplication generated these two genes shortly after the divergence of amphibians and amniotes. The evolutionary history of the receptor family differs from that of their cognate ligands. GPR39 diverges first, and an ancestral receptor gives rise to receptors classified as fish-specific clade A, GHSR and MLNR by successive gene duplications occurring before the divergence of tetrapods and ray-finned fish. The ghrelin/GHSR system is maintained and functionally conserved from fish to mammals. Motilin-MLNR specificity must have arisen by ligand-receptor coevolution after the MLN hormone gene diverged from the GHRL gene in the amniote lineage. Conserved molecular machinery can give rise to new neuroendocrine response mechanisms by the co-option of duplicated genes. Gene duplication is both parsimonious and creative in producing elements for evolutionary tinkering and plays a major role in gene co-option, thus aiding the evolution of greater biological complexity.

关键词：基因重复生长素胃动素受体选项演变家庭进化模式

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胰高血糖素样肽1和肠道菌群（英文）

中国药理学与毒理学杂志 2016年第6期30卷 691-702,608页

作者：金天如 Division of Advanced Diagnostics Toronto General Research Institute University Health Network banting and best diabetes centre Faculty of Medicine University of Toronto Department of Physiology University of Toronto

胃肠道生产20多种肽类激素。其中,胰高血糖素样肽1(GLP-1)在过去的30年里受到最多关注。人们对GLP-1以及另一肠道激素葡萄糖依赖性促胰岛素肽(GIP)功能的研究已导致了两类新的糖尿病治疗药物的开发,分别称为GLP-1R激动剂和DPP-Ⅳ抑制剂... 详细信息

胃肠道生产20多种肽类激素。其中,胰高血糖素样肽1(GLP-1)在过去的30年里受到最多关注。人们对GLP-1以及另一肠道激素葡萄糖依赖性促胰岛素肽(GIP)功能的研究已导致了两类新的糖尿病治疗药物的开发,分别称为GLP-1R激动剂和DPP-Ⅳ抑制剂。肠道的这些内分泌细胞不是聚集在内分泌腺体中,而是广泛分布在整个胃肠道中,从而与"外部"环境包括食物以及肠道菌群充分接触。本文简要介绍了GLP-1以及营养成分如何调节其分泌,并重点讨论了肠道环境如何影响GLP-1的产生和分泌,包括肠道菌群的贡献。

关键词：胰高血糖素样肽1 肠促胰岛素肽 L细胞模型肠道菌群短链脂肪酸

Hepatic hormone FGF21 and its analogues in clinical trials

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Chronic Diseases and Translational Medicine 2022年第1期8卷 19-25页

作者： Weijuan Shao Tianru Jin Division of Advanced Diagnostics Toronto General Hospital Research InstituteUniversity Health NetworkTorontoOntarioCanada Department of Physiology Faculty of MedicineUniversity of TorontoTorontoOntarioCanada banting and best diabetes Center Faculty of MedicineUniversity of TorontoTorontoOntarioCanada

Fibroblast growth factor 21(FGF21)is a fasting or stress inducible metabolic hormone produced mainly in the *** plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1(FGFR1)andβ-klotho(KLB).For the past decade,great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes(T2D),obesity,and more importantly,nonalcoholic fatty liver disease(NAFLD).Here we have reviewed FGF21 gene and protein structures,its expression pattern,cellular signaling cascades that mediate FGF21 production and *** have then summarized the six clinical trials utilizing four FGF21 ***,two recent literatures on the development of GLP-1 and FGF21 dual agonists were presented briefly.

关键词： dual agonists fibroblast growth factor 21 lipid metabolism metabolic diseases

Diversification of Sisorid catfishes(Teleostei: Siluriformes)in relation to the orogeny of the Himalayan Plateau

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Science Bulletin 2016年第13期61卷 991-1002页

作者： Chuanjiang Zhou Xuzhen Wang Xiaoni Gan Yaping Zhang David M.Irwin Richard L.Mayden Shunping He Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences Institute of HydrobiologyChinese Academy of Sciences Key Laboratory of Freshwater Fish Reproduction and Development (Southwest University) Ministry of EducationSchool of Life Science Southwest University State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences College of Fisheries Henan Normal University Department of Laboratory Medicine and Pathobiology University of Toronto banting and best diabetes centre University of Toronto Department of Biology 3507 Laclede Ave. Saint Louis University

Abstract Sisorid catfishes are primarily limited in distribution to rivers of the Himalayan region and Tibetan Plateau. These species have external morphologies that are adapted for extremely fast-flowing riverine systems. Given the diversity of the group and the above qualities of these catfishes, this lineage serves as an ideal group for inferring the geological history of this region based on their phylogenetic relationships reflecting evolu- tionary history. We sequenced the complete mitochondrial genome and four nuclear genes of representative sisorids distributed across river systems in China. Phylogenetic analyses strongly support the monophyly of the Sisoridae and the glyptosternoids. An analysis of the reconstructed ancestral states derived from inferred genealogical relationships suggests that the evolution of this lineage was accompanied by convergent evolution in morphological traits that were presumably in response to environmental pressure involving the rapid flowing river system that were generated during the uplift of the Tibetan Plateau （UTP）. Molecular dating indicates that the Chinese sisorids and the glyptosternoids originated at the later Miocene （~ 10.9-9.8 Mya）, and with further biogeographic analyses indicates that the species of Sisoridae likely originated from a widely distributed ancestor. Moreover, the divergence of the Sisoridae in China can be divided into two phases consis- tent with the UTP. All of these results indicate that the diversification and dispersal events in this lineage occurred as a result of drainage systems formed during and after the UTP in the late Miocene and Quaternary periods.

关键词： Phylogeny. Diversification and dispersal.Biogeography - Divergence time estimation ~ TibetanPlateau ~ Sisoridae ~ Catfish

The anti-inflammatory feature of glucagon-like peptide-1 and its based diabetes drugs-Therapeutic potential exploration in lung injury

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4040-4055页

作者： Juan Pang Jia Nuo Feng Wenhua Ling Tianru Jin Department of Nutrition School of Public HealthSun Yat-sen UniversitynstituteGuangzhou 510080China Division of Advanced Diagnostics Toronto General Hospital Research IUniversity Health NetworkToronto M5G 1L7Canada Department of Physiology Faculty of MedicineUniversity of TorontoToronto M5S 1AICanada banting and best diabetes centre Faculty of MedicineUniversity of ToromtoToronto M5G 2C4Canada

Since 2005,GLP-1 receptor(GLP-IR)agonists(GLP-IRAs)have been developed as therapeutic agents for type 2 diabetes(T2D).GLP-IR is not only expressed in pancreatic islets but also other organs,especially the ***,controversy on extra pancreatic GLP-IR expression still needs to be further resolved,utilizing different tools including the use of more reliable GLP-IR antibodies in immune-staining and ***-pancreatic expression of GLP-IR has triggered extensive investigations on extra-pancreatic functions of GLP-1RAs,aiming to repurpose them into therapeutic agents for other *** studies have demonstrated promising anti-infammatory features of *** those features are directly mediated by GLP-IR expressed in immune cells also remains *** a brief review on GLP-1 as an incretin hormone and the development of GLP-IRAs as therapeutic agents for T2D,we have summarized our current understanding of the antiinflammatory features of GLP-IRAS and commented on the controversy on extra-pancreatic GLP-IR *** main part of this review is a literature discussion on GLP-IRA utilization in animal models with chronic airway diseases and acute lung injuries,including studies on the combined use of mesenchymal stem cell(MSC)based *** is followed by a brief summary.

关键词： Anti inflammation Exenatide GLP-1R GLP-1RAs Liraglutide Lung injury MSC-based therapy TxNIP