《科學》（20190621出版）一周論文導讀

翻譯 | 唐一塵

Science, 21 JUNE 2019, VOL 364, ISSUE 6446

《科學》2019年6月21日，第6446期364卷

反芻動物基因組

RuminantGenomes

Large-scale ruminantgenome sequencing provides insights into their evolution and distinct traits

大規模反芻動物基因組測序為研究該動物的進化和特性提供了新視角

作者：Lei Chen、QiangQiu、Yu Jiang、Wen Wang，etal

鏈接：

https://science.sciencemag.org/content/364/6446/eaav6202

摘要：

反芻動物是一群高度成功且多元的哺乳動物，它們對農業、自然保護和生物醫藥都具重要性。反芻動物包括許多知名的馴養和野生分類群，如牛、山羊、馴鹿和長頸鹿等。

它們棲息在地球上的大部分地方，其中包括黑暗且寒冷的北極凍原。然而，這些反芻動物的演化起源和造成其獨特性狀的遺傳學內容仍然相對未知。

本研究組裝了44種反芻動物的基因組，它們包含所有6個反芻類家族，這一數據集包含了超過40萬億個鹼基對。

研究人員用相關基因數據創建了一個該群組動物的用時間校準的系統進化樹，它能解析許多反芻動物屬的演化史。

有趣的是，這些結果揭示，在近10萬年前，反芻動物種群發生大幅衰減。這些種群數的減少與人類向非洲之外遷徙的時間相符，或佐證了早期人類對各種物種的影響。

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)

北極馴鹿的生物學適應

作者：Zeshan Lin、LeiChen、Xianqing Chen、Wen Wang、Zhipeng Li，etal

鏈接：

https://science.sciencemag.org/content/364/6446/eaav6312

摘要：

馴鹿是馴鹿屬唯一物種，主要分布於歐亞大陸、西伯利亞南部和北美大陸的北緯48度以北的苔原、山地和林區，是北極和亞北極地區大型反芻動物區系的典型代表。

但馴鹿馴順的性格，適應北極極端環境和雌性長角的分子遺傳機制，此前並不清楚。

本研究分析了馴鹿適應北極和溫順特性的遺傳機制。結果發現，馴鹿的節律通路中的核心調控基因（PER2）發生了特異性突變，從而無法與另一個節律核心基因結合。

這讓馴鹿喪失了晝夜節律分子鐘，從而能適應北極極晝和極夜的環境。

研究還發現，馴鹿的一個角生長關鍵基因CCND1上游增加了一個雄性激素受體結合區域，這可能使得馴鹿在更低的雄激素水平下能促成雌性馴鹿長角。

此外，馴鹿的維生素D代謝和溫順性相關的數個基因也發生獨特的突變及/或處於正向選擇之下。

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

反芻動物的角及其快速再生的遺傳基礎

作者：Yu Wang、ChenzhouZhang、Nini Wang、Wen Wang、Qiang Qiu，etal

鏈接：

https://science.sciencemag.org/content/364/6446/eaav6335

摘要：

反芻動物擁有骨性角，儘管這些角具有相同的組成及處於顱骨，但它們的形成與功能在數個反芻族類中是不同的。例如，那些鹿所生長的茸角能快速生長（每天會生長多達2.5厘米），再生生物學對其特別感興趣。

通過將來自頭部長角的反芻動物家族的221個轉錄物組及趨同性缺失的角的2個世系的基因組與基因組背景進行比較，研究發現，牛科動物的角與鹿科動物的茸角共有類似的遺傳學和細胞學根源。

但茸角組織的再生性能是通過對癌症相關信號通路的獨特利用和腫瘤抑制基因的高度表達而成為可能的。這些結果為研究人員尋找讓組織再生但又不會生長癌症的基因及調控序列提供了線索。

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.

生物學Biology

The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice

聚糖CA19-9促進小鼠胰腺炎和胰腺癌的發生

作者：Dannielle D. Engle、Hervé Tiriac、David A. Tuveson，etal

鏈接：

https://science.sciencemag.org/content/364/6446/1156

摘要：

CA19-9是出現在許多蛋白質上的聚糖碳水化合物抗原，它通常在胰腺中呈低水平表達。然而，胰腺疾病（包括胰腺癌）的患者常常會出現該抗體的血濃度增加。

因此，它成為這類疾病的少數生物標記之一，但CA19-9如何與疾病的病理髮生關聯則仍不十分清楚。由於小鼠本身不表達CA19-9，因此一直沒有合適的小鼠模型用於對研究這一關係。

本研究研發了轉基因小鼠模型，它們能複製在人類胰腺癌患者中所觀察到的CA19-9的升高。

研究人員證明，CA19-9在小鼠中的表達會導致嚴重的胰腺炎和表皮生長因子受體信號傳導的超活化，後者是胰腺癌的一個已知的驅動因子。儘管CA19-9介導的胰腺癌可被CA19-9抗體逆轉，但同時含有某個腫瘤基因的表達CA19-9的轉基因小鼠會發生胰腺癌。

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 Kras^G12Doncogene 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 muciniphilainduces intestinal adaptive immune responses during homeostasis

Akkermansia muciniphila能在體內平衡過程中引起腸道適應性免疫反應

作者：Eduard Ansaldo、LeiannaC. Slayden、Gregory M. Barton，etal

鏈接：

https://science.sciencemag.org/content/364/6446/1179

摘要：

腸道適應性免疫反應影響宿主健康，但目前只有少數幾種腸道細菌能在體內平衡過程中誘導同源的適應性免疫反應。

在這裡，研究展示了Akkermansia muciniphila（一種腸道細菌，與宿主代謝和PD-1檢查點免疫治療有關），能在小鼠中誘導免疫球蛋白G1（IgG1）抗體和抗原特異性T細胞反應。

在無菌環境中，T細胞對Akkermansia muciniphila的反應受限於T卵泡輔助細胞。

然而，在傳統小鼠模型中，Akkermansia muciniphila特異性反應依賴於環境，且會出現其他變化。這些發現表明，在內穩態中，環境信號影響T細胞對微生物群的反應，並調節宿主免疫功能。

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.

海洋動物Marineanimal

The small world of global marine fisheries: The cross-boundary consequences of larval dispersal

全球海洋漁業的小世界：幼魚擴散的跨國影響

作者：Nandini Ramesh、JamesA. Rising、Kimberly L. Oremus

鏈接：

https://science.sciencemag.org/content/364/6446/1192

摘要：

許多國家對其魚類的管理十分局限，並將魚類資源視為獨立的、國際專屬經濟區內的資源。然而，魚類並不受限於這種武斷的劃分，魚群間的聯繫通常會遠遠超越行政邊界。

這對其具流動性的幼魚尤其如此，人們對幼魚的跨界聯繫性對漁業的衝擊不甚理解。

本研究對全世界超過700種商業性捕撈魚種的國際連通性和經濟貢獻進行了全球分析，結果揭示了全球漁場內的一個跨洋的「小型世界」 網路。

研究人員用海洋動態建模、網路分析及747個捕撈魚種的生活史數據，確定了國際專屬經濟區間幼魚的播散。

結果表明，幼魚的國際性流動或能解釋相當大數量的魚獲總量（也許每年的價值超過100億美元）。正是因為這種整體漁業的相互依賴形成了一個單一的、全球性網路，其特徵是緊密的相互聯繫和尤其重要的生產力中心。

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

最小海洋脊椎動物的種群動態為珊瑚礁生態系統功能提供了燃料

作者：Simon J. Brandl、Luke Tornabene、Christopher H. R. Goatley，etal

鏈接：

https://science.sciencemag.org/content/364/6446/1189

摘要：

幾個世紀以來，珊瑚礁作為生命綠洲如何在低生產力的海洋中生存，一直困擾著科學家們。答案可能在於珊瑚礁內部營養循環和/或遠洋區的輸入。

本研究綜合薈萃分析、野外數據和種群模型，發現海洋中最小的脊椎動物——珊瑚礁魚類，能通過從遠洋環境中大量供應幼魚，促進礁魚內部生物量的產生。具體地說，儘管成年礁魚的繁殖能力有限，但這種魚的幼魚在近礁海區幼魚中佔2/3。

這種數量驚人的礁魚幼魚通過快速生長和極端的死亡率為珊瑚礁的營養動力學提供了燃料。雖然，它們經常被忽視，但其獨特的種群動態可能使它們成為現代珊瑚礁生態系統功能的基石。

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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