小柯机器人

切换到桌面版
科学家发现对人类和祖先脊椎动物的左右不对称性分配至关重要的遗传模块
2021-12-19 23:47
来源：小柯机器人

新加坡A*STAR研究所Bruno Reversade等研究人员合作发现对人类和祖先脊椎动物的左右不对称性分配至关重要的遗传模块。相关论文于2021年12月13日在线发表在《自然—遗传学》杂志上。

研究人员表示，脊椎动物的左右轴在胚胎发育过程中由一个短暂的器官指定：左右组织者（LRO）。包括鱼类、两栖类、啮齿类和人类在内的物种在LRO中部署了运动纤毛来打破双边对称，而爬行动物、鸟类、偶蹄类哺乳动物和鲸类被认为具有没有运动纤毛的LRO。
 
研究人员搜索了在脊椎动物进化过程中丧失的基因，并确定了五个编码细胞外蛋白的基因，包括一个推定的蛋白酶，其功能至今未知，研究人员将其命名为ciliated left–right organizer metallopeptide (CIROP)。结果表明CIROP在纤毛虫的LRO中特异性表达。在斑马鱼和爪哇鱼中，CIROP仅在左侧需要，在向左流动的下游，但在DAND5的上游，即第一个不对称表达的基因。研究人员进一步确定了21名功能缺失的CIROP突变人类患者，这些患者表现为隐性situs anomalies。这些研究结果表明了一个祖先遗传模块的存在，该模块在脊椎动物进化过程中两次消失，但在人类中对区分左和右仍然至关重要。
 
附：英文原文

Title: Discovery of a genetic module essential for assigning left–right asymmetry in humans and ancestral vertebrates

Author: Szenker-Ravi, Emmanuelle, Ott, Tim, Khatoo, Muznah, de Bellaing, Anne Moreau, Goh, Wei Xuan, Chong, Yan Ling, Beckers, Anja, Kannesan, Darshini, Louvel, Guillaume, Anujan, Priyanka, Ravi, Vydianathan, Bonnard, Carine, Moutton, Sbastien, Schoen, Patric, Fradin, Mlanie, Colin, Estelle, Megarbane, Andr, Daou, Linda, Chehab, Ghassan, Di Filippo, Sylvie, Rooryck, Caroline, Deleuze, Jean-Franois, Boland, Anne, Arribard, Nicolas, Eker, Rukiye, Tohari, Sumanty, Ng, Alvin Yu-Jin, Rio, Marlne, Lim, Chun Teck, Eisenhaber, Birgit, Eisenhaber, Frank, Venkatesh, Byrappa, Amiel, Jeanne, Crollius, Hugues Roest, Gordon, Christopher T., Gossler, Achim, Roy, Sudipto, Attie-Bitach, Tania, Blum, Martin, Bouvagnet, Patrice, Reversade, Bruno

Issue&Volume: 2021-12-13

Abstract: The vertebrate left–right axis is specified during embryogenesis by a transient organ: the left–right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left–right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans.

DOI: 10.1038/s41588-021-00970-4

Source: https://www.nature.com/articles/s41588-021-00970-4

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex


本期文章：《自然—遗传学》：Online/在线发表

分享到:

0