A Caenorhabditis elegans wild type defies the temperature-size rule owing to a single nucleotide polymorphism in tra-3.
A Caenorhabditis elegans wild type defies the temperature-size rule owing to a single nucleotide polymorphism in tra-3.
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DOI：
10.1371/journal.pgen.0030034
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发表时间：
2007-03-02
期刊：
影响因子：
4.5
通讯作者：
Bakker J
中科院分区：
文献类型：
--
作者：
Kammenga JE;Doroszuk A;Riksen JA;Hazendonk E;Spiridon L;Petrescu AJ;Tijsterman M;Plasterk RH;Bakker J
变温动物依靠周围的温度来获取体温。生物学中的一个关键问题是，为什么大多数变温动物在较低的温度下长大，这种现象被称为温度-尺寸规则。由于温度几乎影响生物体内的所有过程，目前解释这一现象的理论既多样又复杂，而且往往是基于相反的假设。虽然被广泛研究，但温度-尺寸规则的分子遗传控制是未知的。我们发现秀丽隐杆线虫野生型N2符合温度-尺寸规则，而野生型CB4856则不符合。利用基于N2 × CB4856重组自交系的候选基因方法，结合突变分析、互补和转基因研究，我们发现tra-3的单核苷酸多态性导致编码的calpain样蛋白酶F96L突变。该突变减弱了CB4856在低温下生长的能力。同源性模型预测F96L通过破坏DII-A结构域来降低TRA-3活性。这些数据表明，变温动物对温度变化的体型适应可能没有以前认为的那么复杂，因为一种微妙的野生型多态性调节了体型对温度的反应。这些发现为从分子角度理解温度-尺寸规律迈出了新的一步，这一规律困扰了生物学家几十年。生物学家对身体大小的变化很感兴趣，这并不奇怪，因为身体大小的范围从细菌到蓝鲸都有。即使在同一物种中，体型大小也会有很大差异。这种种内变异很有趣，因为它表明体型和环境之间有很强的联系。早在1847年，伯格曼就注意到哺乳动物在较冷的环境中往往体型较大。最近在变温动物身上也发现了类似的关系，变温动物依靠周围环境的温度来获取体温，超过85%的被研究物种在较低的温度下变大。这种现象被称为“温度-尺寸定律”，它重新引起了人们对温度如何影响体型的兴趣。然而，温度-尺寸规则的控制仍然是个谜，提出的假设也没有定论。在本文中，作者表明一个基因的单个核酸变化是调节线虫的温度-大小规则所必需的。利用蛋白质模型，他们还表明，DNA的这种细微变化降低了编码蛋白质的功能。这些数据表明，温度适应可能比以前认为的简单得多，也远没有那么复杂。
Ectotherms rely for their body heat on surrounding temperatures. A key question in biology is why most ectotherms mature at a larger size at lower temperatures, a phenomenon known as the temperature–size rule. Since temperature affects virtually all processes in a living organism, current theories to explain this phenomenon are diverse and complex and assert often from opposing assumptions. Although widely studied, the molecular genetic control of the temperature–size rule is unknown. We found that the Caenorhabditis elegans wild-type N2 complied with the temperature–size rule, whereas wild-type CB4856 defied it. Using a candidate gene approach based on an N2 × CB4856 recombinant inbred panel in combination with mutant analysis, complementation, and transgenic studies, we show that a single nucleotide polymorphism in tra-3 leads to mutation F96L in the encoded calpain-like protease. This mutation attenuates the ability of CB4856 to grow larger at low temperature. Homology modelling predicts that F96L reduces TRA-3 activity by destabilizing the DII-A domain. The data show that size adaptation of ectotherms to temperature changes may be less complex than previously thought because a subtle wild-type polymorphism modulates the temperature responsiveness of body size. These findings provide a novel step toward the molecular understanding of the temperature–size rule, which has puzzled biologists for decades. Biologists are fascinated by variation in body size, which is hardly surprising, considering that the range of body sizes spans orders of magnitude from bacteria to blue whales. Even within species, body sizes can vary dramatically. This intraspecies variation is intriguing because it suggests strong associations between body size and environment. Already in 1847, Bergmann noticed that mammals tend to be larger in colder environments. More recently similar relationships were found for ectotherms, which rely for their body heat on the temperature of their surroundings, where more than 85% of the species studied grew larger at lower temperatures. This phenomenon, dubbed the temperature–size rule, has caused a renewed interest to understand how temperature affects body size. Yet the control of the temperature–size rule remains enigmatic, and the hypotheses proposed have been inconclusive. In this paper the authors show that a single nucleic acid change in one gene is required for regulation of the temperature–size rule in the nematode C. elegans. Using protein modelling they also show that this subtle change in DNA decreases the function of the encoded protein. The data suggest that temperature adaptation can be simple and far less complex than previously thought.
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