Evolutionary principles of modular gene regulation in yeasts.
Evolutionary principles of modular gene regulation in yeasts.
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DOI：
10.7554/elife.00603
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发表时间：
2013-06-18
期刊：
影响因子：
7.7
通讯作者：
Regev A
中科院分区：
文献类型：
--
作者：
Thompson DA;Roy S;Chan M;Styczynsky MP;Pfiffner J;French C;Socha A;Thielke A;Napolitano S;Muller P;Kellis M;Konieczka JH;Wapinski I;Regev A
基因调控的差异在进化中起着重要作用。在这里，我们使用了一个系统发育的框架来测量mRNA的档案，在15种酵母菌的子囊菌门和重建的演变，他们的模块化的监管程序沿着的时间过程中的葡萄糖超过3亿年的增长。我们发现，模块已分化成比例的系统发育距离，伴随着生活方式和倍性的变化，特别是在碳代谢的基因调控的显着变化。旁系同源物对监管分歧有很大的贡献，通常是在它们复制后很短的时间内。来自全基因组复制（WGD）事件的旁系同源物具有在较长跨度上延伸的独特的实质性贡献。类似的模式发生时，考虑到在八个物种中测量的热休克调节程序的演变，这表明这些是一般的进化原则。生物令人难以置信的多样性掩盖了它们的基因非常相似的事实。http://dx.doi.org/10.7554/eLife.00603.001在20世纪70年代，玛丽-克莱尔·金和艾伦·威尔逊提出，一个被称为基因调控的过程决定了基因何时、何地以及如何表达为蛋白质，这是造成这种多样性的原因。40年后，基因调控在进化中的核心作用已在包括细菌、真菌、苍蝇和哺乳动物在内的广泛物种中得到证实，尽管对细节仍知之甚少。近年来，有人提出，基因的复制，有时是整个基因组的复制，对基因调控在许多不同物种进化中所起的作用有着至关重要的影响。子囊菌门真菌因其多样性而独特地适合于遗传和进化的研究--它们包括C。白色念珠菌，一种在人类口腔和肠道中发现的真菌，以及各种酵母菌，因为它们的许多基因组已经被测序。此外，它们的基因组相对较小，这简化了研究其在进化过程中如何变化的任务。我们还知道，在生命之树的这个分支中，物种在整个基因组被复制的事件前后发生了分化。子囊菌门真菌在有氧生长期间以不同的方式使用葡萄糖作为碳源。大多数，包括C。白色念珠菌是呼吸性的，并且依赖于氧化磷酸化过程来产生能量。然而，包括S.酿酒酵母和酿酒酵母。粟酒裂殖酵母是两种广泛用作模式生物的酵母，它们喜欢发酵葡萄糖，即使在有氧气的情况下。喜欢后一种呼吸发酵生活方式的物种至少独立进化了两次：一次是在导致S. cerevisiae和S.粟酒裂殖酵母和其他分裂酵母进化。Thompson等人测量了15种不同酵母的mRNA谱，并重建了基因组（模块）的调控如何在3亿多年的时间里进化。他们发现，模块已经与进化时间成比例地分化，基因调控的显著变化与生活方式的变化（特别是碳代谢的变化）和全基因组复制事件有关。基因复制事件导致了基因旁系同源基因在基因组不同位置的相同基因，这些对不同形式的基因调控的进化做出了重大贡献，特别是在复制事件之后。此外，在全基因组复制事件中产生的旁系同源物在更长的时间内导致了更大的变化。在八个物种中，在参与热休克反应的基因调控中观察到类似的模式，这表明这些是一般的进化原则。与呼吸发酵生活方式相关的基因表达变化也可能对我们理解癌症有影响：健康细胞依赖氧化磷酸化产生能量，而与酵母细胞相似，大多数癌细胞依赖呼吸发酵。此外，酵母细胞和癌细胞都通过使用葡萄糖进行生物合成以支持细胞分裂来支持其快速生长和增殖，尽管这一过程尚未完全理解。另一方面，正常细胞主要使用葡萄糖作为能量，并且倾向于不快速分裂。Thompson等人发现，在两条生物合成途径中编码酶的基因--一条产生DNA复制所必需的核苷酸，一条合成甘氨酸--在呼吸发酵酵母中被诱导，但在呼吸酵母细胞中被抑制。当正常细胞变成癌细胞时，在相同的两个通路中观察到类似的变化，这一事实表明这些通路在癌症的发展中起着重要作用。Thompson等人开发的框架也可用于探索其他物种和生物过程中基因调控的进化。DOI：http://dx.doi.org/10.7554/eLife.00603.002网站
Divergence in gene regulation can play a major role in evolution. Here, we used a phylogenetic framework to measure mRNA profiles in 15 yeast species from the phylum Ascomycota and reconstruct the evolution of their modular regulatory programs along a time course of growth on glucose over 300 million years. We found that modules have diverged proportionally to phylogenetic distance, with prominent changes in gene regulation accompanying changes in lifestyle and ploidy, especially in carbon metabolism. Paralogs have significantly contributed to regulatory divergence, typically within a very short window from their duplication. Paralogs from a whole genome duplication (WGD) event have a uniquely substantial contribution that extends over a longer span. Similar patterns occur when considering the evolution of the heat shock regulatory program measured in eight of the species, suggesting that these are general evolutionary principles. DOI: http://dx.doi.org/10.7554/eLife.00603.001 The incredible diversity of living creatures belies the fact that their genes are quite similar. In the 1970s Mary-Claire King and Allan Wilson proposed that a process called gene regulation—which determines when, where and how genes are expressed as proteins—is responsible for this diversity. Four decades later, the central role of gene regulation in evolution has been confirmed in a wide range of species including bacteria, fungi, flies and mammals, although the details remain poorly understood. In recent years it has been suggested that the duplication of genes—and sometimes the duplication of whole genomes—has had a crucial influence on the part played by gene regulation in the evolution of many different species. Ascomycota fungi are uniquely suited to the study of genetics and evolution because of their diversity—they include C. albicans, a fungus that is found in the human mouth and gut, and various species of yeast—and because many of their genomes have already been sequenced. Moreover, their genomes are relatively small, which simplifies the task of working out how it has changed over the course of evolution. It is also known that species in this branch of the tree of life diverged before and after an event in which a whole genome was duplicated. Ascomycota fungi use glucose as a source of carbon in different ways during aerobic growth. Most, including C. albicans, are respiratory and rely on oxidative phosphorylation processes to produce energy. However, a small number—including S. cerevisiae and S. pombe, two types of yeast that are widely used as model organisms—prefer to ferment glucose, even when oxygen is available. Species that favor the latter respiro-fermentative lifestyle have evolved independently at least twice: once after the whole genome duplication event that lead to S. cerevisiae, and once when S. pombe and the other fission yeasts evolved. Thompson et al. have measured mRNA profiles in 15 different species of yeast and reconstructed how the regulation of groups of genes (modules) have evolved over a period of more than 300 million years. They found that modules have diverged proportionally to evolutionary time, with prominent changes in gene regulation being associated with changes in lifestyle (especially changes in carbon metabolism) and a whole genome duplication event. Gene duplication events result in gene paralogs—identical genes at different places in the genome—and these have made significant contributions to the evolution of different forms of gene regulation, especially just after the duplication event. Moreover, the paralogs produced in whole genome duplication events have resulted in bigger changes over longer periods of time. Similar patterns were observed in the regulation of the genes involved in the response to heat shock in eight of the species, which suggests that these are general evolutionary principles. The changes in gene expression associated with the respiro-fermentative lifestyle may also have implications for our understanding of cancer: healthy cells rely on oxidative phosphorylation to produce energy whereas, similar to yeast cells, most cancerous cells rely on respiro-fermentation. Furthermore, yeast cells and cancer cells both support their rapid growth and proliferation by using glucose for biosynthesis to support cell division, although this process is not fully understood. Normal cells, on the other hand, use glucose primarily for energy and tend not to divide rapidly. Thompson et al. found that the genes encoding enzymes in two biosynthetic pathways—one that produces the nucleotides necessary for DNA replication, and one that synthesizes glycine—are induced in respiro-fermentative yeasts but repressed in respiratory yeast cells. The fact that similar changes are observed in the same two pathways when normal cells become cancer cells suggests that these pathways have an important role in the development of cancer. The framework developed by Thompson et al. could also be used to explore the evolution of gene regulation in other species and biological processes. DOI: http://dx.doi.org/10.7554/eLife.00603.002