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Genomic insights into adaptation to bipedal saltation and desert-like habitats of jerboas

Science China Life Sciences 2024年

作者： Simin Chai Yujie Chong Daiqing Yin Qiang Qiu shixia xu Guang Yang Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) Jiangsu Key Laboratory for Biodiversity and Biotechnology School of Life Sciences Nanjing Normal University School of Ecology and Environment Northwestern Polytechnical University

Jerboas is a lineage of small rodents displaying atypical mouse-like morphology with elongated strong hindlimbs and short forelimbs. They have evolved obligate bipedal saltation and acute senses, and been well-adapted to vast desert-like habitats. Using a newly sequenced chromosome-scale genome of the Mongolian five-toed jerboa(Orientallactaga sibirica), our comparative genomic analyses and in vitro functional assays showed that the genetic innovations in both protein-coding and non-coding regions played an important role in jerboa morphological and physiological adaptation. Jerboa-specific amino acid substitutions, and segment insertions/deletions(indels) in conserved non-coding elements(CNEs) were found in components of proteoglycan biosynthesis pathway(XYLT1 and CHSY1), which plays an important role in limb development. Meanwhile, we found specific evolutionary changes functionally associated with energy or water metabolism(e.g., specific amino acid substitutions in ND5 and indels in CNEs physically near ROR2) and senses(e.g., expansion of vomeronasal receptors and the FAM136A gene family) in jerboas. Further dual-luciferase reporter assay verified that some of the CNEs with jerboa-specific segment indels exerted a significantly different influence on luciferase activity, suggesting changes in their regulatory function in jerboas. Our results revealed the potential molecular mechanisms underlying jerboa adaptation since the divergence from the Eocene-Oligocene transition, and provided more resources and new insights to enhance our understanding of the molecular basis underlying the phenotypic diversity and the environmental adaptation of mammals.

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The position of tree shrews in the mammalian tree:Comparing multi-gene analyses with phylogenomic results leaves monophyly of Euarchonta doubtful

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Integrative Zoology 2015年第2期10卷 186-198页

作者： xuming ZHOU Fengming SUN shixia xu Guang YANG Ming LI Key laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijing China University of Chinese Academy of Sciences Beijing China CUHK-BGI Innovation Institute of Trans-omics Chinese University of Hong KongShatinNew TerritoriesHong KongChina BGI-Shenzhen ShenzhenChina Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life SciencesNanjing Normal UniversityNanjingChina

The well-accepted Euarchonta grandorder is a pruned version of Archonta nested within the Euarchontoglires(or Supraprimates)clade.At present,it includes tree shrews(Scandentia),flying lemurs(Dermoptera)and primates(Primates).Here,a phylogenomic dataset containing 1912 exons from 22 representative mammals was compiled to investigate the phylogenetic relationships within this group.Phylogenetic analyses and hypothesis testing suggested that tree shrews can be classified as a sister group to Primates or to Glires or even as a basal clade within Euarchontoglires.Further analyses of both modified and original previously published datasets found that the phylogenetic position of tree shrews is unstable.We also found that two of three exonic indels reported as synapomorphies of Euarchonta in a previous study do not unambiguously support the monophyly of such a clade.Therefore,the monophyly of both Euarchonta and Sundatheria(Dermoptera+Scandentia)are suspect.Molecular dating and divergence rate analyses suggested that the ancestor of Euarchontoglires experienced a rapid divergence,which may cause the unresolved position of tree shrews even using the whole genomic data.

关键词： Euarchonta Euarchontoglires phylogenomics tree shrews

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Tramadol reinforces antidepressant effects of ketamine with increased levels of brain-derived neurotrophic factor and tropomyosin-related kinase B in rat hippocampus

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Frontiers of Medicine 2012年第4期6卷 411-415页

作者： Chun Yang Xiaomin Li Nan Wang shixia xu Jianjun Yang Zhiqiang Zhou Department of Anesthesiology Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002China

Ketamine exerts rapid and robust antidepressant properties in both animal models and depressed patients and tramadol possesses potential antidepressant effects.Brain-derived neurotrophic factor(BDNF)is an important biomarker for mood disorders and tropomyosin-related kinase B(TrkB)is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.Immobility time of rats receiving different treatment in the forced swimming test(FST)was observed.Levels of BDNF and TrkB in hippocampus were measured by enzyme linked immunosorbent assay.Results showed that tramadol(5 mg/kg)administrated alone neither elicited antidepressant effects nor altered BDNF or TrkB level.However,pretreatment with tramadol(5 mg/kg)enhanced the ketamine(10 mg/kg)-elicited antidepressant effects and upregulated the BDNF and TrkB levels in hippocampus.In conclusion,tramadol pretreatment reinforces the ketamine-elicited antidepressant effects,which is associated with the increased levels of BDNF and TrkB in rat hippocampus.

关键词： tramadol ketamine antidepressant brain-derived neurotrophic factor tropomyosin-related kinase B

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Molecular evolution of spermatogenesis-related genes in abdominal testicular mammals supports the cooling hypothesis

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Journal of Genetics and Genomics 2021年第12期48卷 1139-1141页

作者： Xiaoyue Ding Huiyuan Wei xu Zhou Long Gu Fangfang Yu Yu Zheng shixia xu Guang Yang Wenhua Ren Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life SciencesNanjing Normal UniversityNanjing 210023China

Testes,which are mainly responsible for producing sperm and secreting male hormones,are the functional center of the male reproductive system in mammals.During embryonic development in mammals with descended testes,th... 详细信息

关键词： cavity hypothesis

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Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications

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Integrative Zoology 2018年第1期13卷 21-35页

作者： Kui LI Xiaohui SUN Meixiu CHEN Yingying SUN Ran TIAN Zhengfei WANG shixia xu Guang YANG Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life SciencesNanjing Normal UniversityNanjing 210023China

The diversity of body plans of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats,including terrestrial,aerial and aquatic habitats.However,the genetic basis of those phenotypic modifications,which have occurred during mammalian evolution,remains poorly explored.In the present study,we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and the main regulatory factors(Mll,Bmi1 and E2f6)that control the expression of Hox genes.A deflected density of repetitive elements and lineage-specific radical mutations of Mll have been determined in marine mammals with morphological changes,suggesting that evolutionary changes may alter Hox gene expression in these lineages,leading to the morphological modification of these lineages.Although no positive selection was detected at certain ancestor nodes of lineages,the increasedωvalues of Hox genes implied the relaxation of functional constraints of these genes during the mammalian evolutionary process.More importantly,49 positively-selected sites were identified in mammalian lineages with phenotypic modifications,indicating adaptive evolution acting on Hox genes and regulatory factors.In addition,3 parallel amino acid substitutions in some Hox genes were examined in marine mammals,which might be responsible for their streamlined body.

关键词： evolutionary changes Hox genes mammals morphological modifications

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Evolutionary genetics of cetacean cancer resistance from Hippo pathway

Evolutionary genetics of cetacean cancer resistance from Hip...

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第十六届全国野生动物生态与资源保护学术研讨会

作者： Linxia Sun Qian Kong Wenhua Ren Guang Yang shixia xu Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life SciencesNanjing Normal University

Cetacea was reported to have lower cancer rate than other mammals and might evolved cancer resistance molecular mechanisms. This study performed evolutionary analysis on the Hippo pathway, a classic tumor suppression signaling, in cetaceans. Evidence of positive selection and cetacean specific changes were identified in cetaceans, which was one reason of cetacean resistance. By contrast, a cetacean specific change A214S led to YAP1 protein locating in cytoplasm that might cause cancer resistance. We suggested cetacean YAP1 might play role in cetacean cancer resistance. Further, tumor suppression genes, cell cycle genes and DNA repair genes were upregulated by overexpressing dolphin YAP1 and zebrafish YAP1 carrying cetacean specific change A214S, which might regulate cancer resistance in cetaceans. This study could provide some novel insights into the evolution of cetacean cancer resistance.

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Adaptive changes in BMAL2 with enhanced awakening ability drive the evolution of unihemispheric slow–wave sleep in mammals

Adaptive changes in BMAL2 with enhanced awakening ability dr...

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第十六届全国野生动物生态与资源保护学术研讨会

作者： Daiqing Yin Biao Zhang Yujie Chong Wenhua Ren shixia xu Guang Yang Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University

Marine mammals, especially cetaceans, have evolved a very special form of sleep characterized by unihemispheric slow–wave sleep(USWS) and a negligible amount or complete absence of rapid-eye-movement(REM) sleep;however, the underlying genetic mechanisms remain unclear. Here, we detected unique, significant selection signatures in basic helix-loop-helix ARNT like 2(BMAL2), a key circadian gene, in marine mammal lineages, and identified two nonsynonymous amino acid substitutions(K204E, K346Q) in the important PAS domain of cetacean BMAL2 by sequence comparison with other mammals. In vitro assays revealed that these cetacean-specific mutations specifically enhanced the response to E-boxlike enhancer and consequently promoted the transcriptional activation of PER2, which is closely linked to sleep regulation. The increased PER2 expression, which was further confirmed both in vitro and in vivo, is beneficial for allowing cetaceans to maintain continuous movement and alertness during sleep. Concordantly, the locomotor activities of zebrafish overexpressing cetacean-specific mutant bmal2 were significantly higher than zebrafish overexpressing the wild-type gene. Subsequently, transcriptome analyses revealed that cetacean-specific mutations caused the upregulation of arousal-related genes and the downregulation of several sleep-promoting genes, which is consistent with the need to suppress whole-brain sleep drive and maintain hemispheric arousal during USWS. Our findings suggest the potential close link between adaptive changes in BMAL2 and the remarkable adaptation of USWS, and may provide novel insights into the genetic basis for the evolution of animal sleep.

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Comparative genomics reveals molecular mechanisms underlying health and reproduction in cryptorchid mammals

Comparative genomics reveals molecular mechanisms underlying...

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第十六届全国野生动物生态与资源保护学术研讨会

作者： Simin Chai Xin Huang Tianzhen Wu shixia xu Wenhua Ren Guang Yang School of Life Sciences Nanjing Normal University

Mammals have wide variations in testicular position, with scrotal testes in some species and ascrotal testes in others. Although cryptorchidism is hazardous to human health, some mammalian taxa are natural cryptorchids. However, the evolution of testicular position and the molecular mechanisms underlying the maintenance of health, including reproductive health, in ascrotal mammals are not clear. In the present study, comparative genomics and evolutionary analyses revealed that genes associated with the extracellular matrix and muscle, contributing to the development of the gubernaculum, were involved in the evolution of testicular position in mammals. Moreover, genes related to testicular position were significantly associated with spermatogenesis and sperm fertility. These genes showed rapid evolution and the signature of positive selection, with specific substitutions in ascrotal mammals. Genes associated with testicular position were significantly enriched in functions and pathways related to cancer, DNA repair, DNA replication, and autophagy. Our results revealed that alterations in gubernaculum development contributed to the evolution of testicular position in mammals and provided the first support for two hypotheses for variation in testicular position in mammals, the "cooling hypothesis", which proposes that the scrotum provides a cool environment for acutely heat-sensitive sperm and the "training hypothesis", which proposes that the scrotum develops the sperm by exposing them to an exterior environment. Further, we identified cancer resistance and DNA repair as potential protective mechanisms in natural cryptorchids. These findings provide general insights into cryptorchidism and have implications for health and infertility both in humans and domestic mammals.

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Comparative analyses of aging-related genes in long-lived mammals provide insights into natural longevity

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The Innovation 2021年第2期2卷 31-39页

作者： Zhenpeng Yu Inge Seim Mengxin Yin Ran Tian Di Sun Wenhua Ren Guang Yang shixia xu Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life SciencesNanjing Normal UniversityNanjing 210023China Integrative Biology Laboratory College of Life SciencesNanjing Normal UniversityNanjing 210023China School of Biology and Environmental Science Faculty of Science and EngineeringQueensland University of TechnologyBrisbaneQLDAustralia

Extreme longevity has evolved multiple times during the evolution of mammals,yet its underlying molecular mechanisms remain largely underexplored.Here,we compared the evolution of 115 aging-related genes in 11 long-lived species and 25 mammals with non-increased lifespan(control group)in the hopes of better understanding the common molecular mechanisms behind longevity.We identified 16 unique positively selected genes and 23 rapidly evolving genes in long-lived species,which included nine genes involved in regulating lifespan through the insulin/IGF-1 signaling(IIS)pathway and 11 genes highly enriched in immune-response-related pathways,suggesting that the IIS pathway and immune response play a particularly important role in exceptional mammalian longevity.Interestingly,11 genes related to cancer progression,including four positively selected genes and seven genes with convergent amino acid changes,were shared by two or more long-lived lineages,indicating that long-lived mammals might have evolved convergent or similar mechanisms of cancer resistance that extended their lifespan.This suggestion was further corroborated by our identifi-cation of 12 robust candidates for longevity-related genes closely related to cancer.

关键词： mammals longevity positive selection IIS pathway immune response cancer resistance

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新《中华人民共和国药品管理法》背景下混合式课堂教学效果探究

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皖南医学院学报 2024年第1期43卷 83-86页

作者：徐诗霞张文叶兰喻丽珍年四辉皖南医学院药学院安徽芜湖241002 皖南医学院第一附属医院弋矶山医院药学部安徽芜湖241001

目的:探讨新《中华人民共和国药品管理法》背景下混合式课堂教学效果。方法:以皖南医学院药学类专业本科生为研究对象,在线发放《药事管理学学科教学情况问卷调查》,统计分析影响药事管理学混合式课堂教学效果的因素。结果:教师素养低... 详细信息

目的:探讨新《中华人民共和国药品管理法》背景下混合式课堂教学效果。方法:以皖南医学院药学类专业本科生为研究对象,在线发放《药事管理学学科教学情况问卷调查》,统计分析影响药事管理学混合式课堂教学效果的因素。结果:教师素养低、听课时间短(≤30 min)、教材滞后、课下未关注医药政策是影响新形势下药事管理学课堂教学效果的危险因素(P<0.05)。结论:药事管理学教学应从及时更新教材、关注药事动态、提高学生上课注意力和听课时间、提高教师队伍整体素质及课下多关注医药政策等角度出发进行实践,不断探索适合药事管理学科特色的方式方法,在提高课堂教学效果的同时,提升教师业务水平,促进教学相长。

关键词：药事管理学中华人民共和国药品管理法教学效果影响因素

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