《科学》（20190621出版）一周论文导读
翻译 | 唐一尘
Science, 21 JUNE 2019, VOL 364, ISSUE 6446
《科学》2019年6月21日，第6446期364卷
反刍动物基因组
RuminantGenomes
Large-scale ruminantgenome sequencing provides insights into their evolution and distinct traits
大规模反刍动物基因组测序为研究该动物的进化和特性提供了新视角
作者：Lei Chen、QiangQiu、Yu Jiang、Wen Wang，etal
链接：
https://science.sciencemag.org/content/364/6446/eaav6202
摘要：
反刍动物是一群高度成功且多元的哺乳动物，它们对农业、自然保护和生物医药都具重要性。反刍动物包括许多知名的驯养和野生分类群，如牛、山羊、驯鹿和长颈鹿等。
它们栖息在地球上的大部分地方，其中包括黑暗且寒冷的北极冻原。然而，这些反刍动物的演化起源和造成其独特性状的遗传学内容仍然相对未知。
本研究组装了44种反刍动物的基因组，它们包含所有6个反刍类家族，这一数据集包含了超过40万亿个碱基对。
研究人员用相关基因数据创建了一个该群组动物的用时间校准的系统进化树，它能解析许多反刍动物属的演化史。
有趣的是，这些结果揭示，在近10万年前，反刍动物种群发生大幅衰减。这些种群数的减少与人类向非洲之外迁徙的时间相符，或佐证了早期人类对各种物种的影响。
Abstract
The ruminants are one of the most successful mammalian lineages, exhibiting morphological and habitat diversity and containing several key livestock species. To better understand their evolution, we generated and analyzed de novo assembled genomes of 44 ruminant species, representing all six Ruminantia families. We used these genomes to create a time-calibrated phylogeny to resolve topological controversies, overcoming the challenges of incomplete lineage sorting. Population dynamic analyses show that population declines commenced between 100,000 and 50,000 years ago, which is concomitant with expansion in human populations. We also reveal genes and regulatory elements that possibly contribute to the evolution of the digestive system, cranial appendages, immune system, metabolism, bodysize, cursorial locomotion, and dentition of the ruminants.
Biological adaptations in the Arctic cervid, the reindeer (Rangifer tarandus)
北极驯鹿的生物学适应
作者：Zeshan Lin、LeiChen、Xianqing Chen、Wen Wang、Zhipeng Li，etal
链接：
https://science.sciencemag.org/content/364/6446/eaav6312
摘要：
驯鹿是驯鹿属唯一物种，主要分布于欧亚大陆、西伯利亚南部和北美大陆的北纬48度以北的苔原、山地和林区，是北极和亚北极地区大型反刍动物区系的典型代表。
但驯鹿驯顺的性格，适应北极极端环境和雌性长角的分子遗传机制，此前并不清楚。
本研究分析了驯鹿适应北极和温顺特性的遗传机制。结果发现，驯鹿的节律通路中的核心调控基因（PER2）发生了特异性突变，从而无法与另一个节律核心基因结合。
这让驯鹿丧失了昼夜节律分子钟，从而能适应北极极昼和极夜的环境。
研究还发现，驯鹿的一个角生长关键基因CCND1上游增加了一个雄性激素受体结合区域，这可能使得驯鹿在更低的雄激素水平下能促成雌性驯鹿长角。
此外，驯鹿的维生素D代谢和温顺性相关的数个基因也发生独特的突变及/或处于正向选择之下。
Abstract
The reindeer is an Arctic species that exhibits distinctive biological characteristics, for which the underlying genetic basis remains largely unknown. We compared the genomes of reindeer against those of other ruminants and nonruminant mammals to reveal the geneticbasis of light arrhythmicity, high vitamin D metabolic efficiency, the antler growth trait of females, and docility. We validate that two reindeer vitamin Dmetabolic genes (CYP27B1 and POR) show signs ofpositive selection and exhibit higher catalytic activity than those of other ruminants. A mutation upstream of the reindeer CCND1 gene endows an extra functional binding motif of the and rogen receptor and thereby may result in female antlers. Furthermore, a mutation (proline-1172→threonine) in reindeer PER2results in loss of binding ability with CRY1, which may explain circadian arrhythmicity in reindeer.
Genetic basis of ruminantheadgear and rapid antler regeneration
反刍动物的角及其快速再生的遗传基础
作者：Yu Wang、ChenzhouZhang、Nini Wang、Wen Wang、Qiang Qiu，etal
链接：
https://science.sciencemag.org/content/364/6446/eaav6335
摘要：
反刍动物拥有骨性角，尽管这些角具有相同的组成及处于颅骨，但它们的形成与功能在数个反刍族类中是不同的。例如，那些鹿所生长的茸角能快速生长（每天会生长多达2.5厘米），再生生物学对其特别感兴趣。
通过将来自头部长角的反刍动物家族的221个转录物组及趋同性缺失的角的2个世系的基因组与基因组背景进行比较，研究发现，牛科动物的角与鹿科动物的茸角共有类似的遗传学和细胞学根源。
但茸角组织的再生性能是通过对癌症相关信号通路的独特利用和肿瘤抑制基因的高度表达而成为可能的。这些结果为研究人员寻找让组织再生但又不会生长癌症的基因及调控序列提供了线索。
Abstract
Ruminants are the only extant mammalian group possessing bony (osseous) headgear. We obtained 221 transcriptomes from bovids and cervids and sequenced three genomes representing the only two pecoran lineages that convergently lack headgear. Comparative analyses reveal that bovid horns and cervid antlers share similar gene expression profiles and a common cellular basis developed from neural crest stem cells. The rapid regenerative properties of antler tissue involve exploitation of oncogenetic pathways, and at the same time some tumor suppressor genes are under strong selection in deer. These results provide insights into the evolutionary origin of ruminant headgear as well as mammalian organ regeneration and oncogenesis.
生物学Biology
The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice
聚糖CA19-9促进小鼠胰腺炎和胰腺癌的发生
作者：Dannielle D. Engle、Hervé Tiriac、David A. Tuveson，etal
链接：
https://science.sciencemag.org/content/364/6446/1156
摘要：
CA19-9是出现在许多蛋白质上的聚糖碳水化合物抗原，它通常在胰腺中呈低水平表达。然而，胰腺疾病（包括胰腺癌）的患者常常会出现该抗体的血浓度增加。
因此，它成为这类疾病的少数生物标记之一，但CA19-9如何与疾病的病理发生关联则仍不十分清楚。由于小鼠本身不表达CA19-9，因此一直没有合适的小鼠模型用于对研究这一关系。
本研究研发了转基因小鼠模型，它们能复制在人类胰腺癌患者中所观察到的CA19-9的升高。
研究人员证明，CA19-9在小鼠中的表达会导致严重的胰腺炎和表皮生长因子受体信号传导的超活化，后者是胰腺癌的一个已知的驱动因子。尽管CA19-9介导的胰腺癌可被CA19-9抗体逆转，但同时含有某个肿瘤基因的表达CA19-9的转基因小鼠会发生胰腺癌。
Abstract
Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these alterations contribute to disease pathogenesis is largely unknown. To study the role of glycan changes in pancreatic disease, we inducibly expressed human fucosyl transferase 3 andβ1,3-galactosyl transferase 5 in mice, reconstituting the glycan sialyl-Lewisa, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression in mice resulted in rapid and severe pancreatitis with hyperactivation of epidermal growth factor receptor (EGFR) signaling. Mechanistically, CA19-9 modification of the matricel lularprotein fibulin-3 increased its interaction with EGFR, and blockade off ibulin-3, EGFR ligands, or CA19-9 prevented EGFR hyperactivation in organoids. CA19-9–mediated pancreatitis was reversible and could be suppressed with CA19-9 antibodies. CA19-9 also cooperated with the KrasG12Doncogene to produce aggressive pancreatic cancer. These findings implicate CA19-9 in the etiology of pancreatitis and pancreatic cancer and nominate CA19-9 as a therapeutic target.
Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis
Akkermansia muciniphila能在体内平衡过程中引起肠道适应性免疫反应
作者：Eduard Ansaldo、LeiannaC. Slayden、Gregory M. Barton，etal
链接：
https://science.sciencemag.org/content/364/6446/1179
摘要：
肠道适应性免疫反应影响宿主健康，但目前只有少数几种肠道细菌能在体内平衡过程中诱导同源的适应性免疫反应。
在这里，研究展示了Akkermansia muciniphila（一种肠道细菌，与宿主代谢和PD-1检查点免疫治疗有关），能在小鼠中诱导免疫球蛋白G1（IgG1）抗体和抗原特异性T细胞反应。
在无菌环境中，T细胞对Akkermansia muciniphila的反应受限于T卵泡辅助细胞。
然而，在传统小鼠模型中，Akkermansia muciniphila特异性反应依赖于环境，且会出现其他变化。这些发现表明，在内稳态中，环境信号影响T细胞对微生物群的反应，并调节宿主免疫功能。
Abstract
Intestinal adaptive immune responses influence host health, yet only a few intestinal bacteria species that induce cognate adaptive immune responses during homeostasis have been identified. Here, we show that Akkermansia muciniphila, an intestinal bacterium associated with systemic effects onhost metabolism and PD-1 checkpoint immuno therapy, induces immunoglobulin G1(IgG1) antibodies and antigen-specific T cell responses in mice. Unlikepreviously characterized mucosal responses, T cell responses toA. muciniphilaare limited to T follicular helper cells in a gnotobiotic setting, without appreciable induction of other T helper fates or migration tothe lamina propria. However,A. muciniphila–specific responses are context dependent and adopt other fates in conventional mice. These findings suggest that, during homeostasis, contextual signals influence T cell responses to the microbiota and modulate host immune function.
海洋动物Marineanimal
The small world of global marine fisheries: The cross-boundary consequences of larval dispersal
全球海洋渔业的小世界：幼鱼扩散的跨国影响
作者：Nandini Ramesh、JamesA. Rising、Kimberly L. Oremus
链接：
https://science.sciencemag.org/content/364/6446/1192
摘要：
许多国家对其鱼类的管理十分局限，并将鱼类资源视为独立的、国际专属经济区内的资源。然而，鱼类并不受限于这种武断的划分，鱼群间的联系通常会远远超越行政边界。
这对其具流动性的幼鱼尤其如此，人们对幼鱼的跨界联系性对渔业的冲击不甚理解。
本研究对全世界超过700种商业性捕捞鱼种的国际连通性和经济贡献进行了全球分析，结果揭示了全球渔场内的一个跨洋的“小型世界” 网络。
研究人员用海洋动态建模、网络分析及747个捕捞鱼种的生活史数据，确定了国际专属经济区间幼鱼的播散。
结果表明，幼鱼的国际性流动或能解释相当大数量的鱼获总量（也许每年的价值超过100亿美元）。正是因为这种整体渔业的相互依赖形成了一个单一的、全球性网络，其特征是紧密的相互联系和尤其重要的生产力中心。
Abstract
Fish stocks are managed within national boundaries and by regional organizations, but the interdependence of stocks between these jurisdictions, especially as a result of larval dispersal, remains poorly explored. We examined the international connectivity of 747 commercially fished taxonomic groups by building a global network of fishlarval dispersal. We found that the world’s fisheries are highly interconnected, forming a small-world network, emphasizing the need for international cooperation. We quantify each country’s dependence on its neighbors in terms of landed value, food security, and jobs. We estimate that more than $10 billion in annual catch from 2005 to 2014 is attributable to these international flows of larvae. The economic risks associated with these dependencies is greatest in the tropics.
Demographic dynamics of the smallest marine vertebrates fuel coral reef ecosystem functioning
最小海洋脊椎动物的种群动态为珊瑚礁生态系统功能提供了燃料
作者：Simon J. Brandl、Luke Tornabene、Christopher H. R. Goatley，etal
链接：
https://science.sciencemag.org/content/364/6446/1189
摘要：
几个世纪以来，珊瑚礁作为生命绿洲如何在低生产力的海洋中生存，一直困扰着科学家们。答案可能在于珊瑚礁内部营养循环和/或远洋区的输入。
本研究综合荟萃分析、野外数据和种群模型，发现海洋中最小的脊椎动物——珊瑚礁鱼类，能通过从远洋环境中大量供应幼鱼，促进礁鱼内部生物量的产生。具体地说，尽管成年礁鱼的繁殖能力有限，但这种鱼的幼鱼在近礁海区幼鱼中占2/3。
这种数量惊人的礁鱼幼鱼通过快速生长和极端的死亡率为珊瑚礁的营养动力学提供了燃料。虽然，它们经常被忽视，但其独特的种群动态可能使它们成为现代珊瑚礁生态系统功能的基石。
Abstract
How coral reefs survive as oases of life in low-productivity oceans has puzzled scientists for centuries. The answer maylie in internal nutrient cycling and/or input from the pelagic zone. Integrating meta-analysis, field data, and population modeling, we show that the ocean’s smallest vertebrates, cryptobenthic reef fishes, promote internal reef fish biomass production through extensive larval supply from the pelagic environment.
Specifically, cryptobenthics account for two-thirds of reef fish larvae in the near-reef pelagic zone despite limited adult reproductive outputs. This overwhelming abundance of cryptobenthic larvae fuels reef tropho dynamics via rapid growth and extreme mortality, producing almost 60% of consumed reef fish biomass. Although cryptobenthics are often overlooked, their distinctive demographic dynamics may make them a cornerstone of ecosystem functioning on modern coral reefs.
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