Peroxisomes: Endosymbiotic Organelles without a Genome?

[9318594]帕尔默：过氧化物酶体是一种在所有动物和其他高等生物的细胞中发现的小的、膜结合的细胞器。过氧化物酶体没有自己的基因组，但许多重要的生化反应和酶（由核基因编码）发生在过氧化物酶体内，大量的人类疾病，大多数是致命的，是由过氧化物酶体功能缺陷引起的。虽然我们对过氧化物酶体的功能了解很多，但我们对它的起源却一无所知。这个项目试图通过收集证据来检验关于过氧化物酶体起源的两种相互竞争的假设来纠正这种情况：1)它是由代谢酶的一个子集的内部区隔产生的，或者2)它像叶绿体和线粒体一样，是内共生产生的，即由原始真核细胞永久摄取细菌（变成过氧化物酶体）。在初步研究中，我们已经确定了四种过氧化物酶体蛋白，它们与细菌同源物具有高度的相似性，从而为假设2提供了支持性的证据。为了对过氧化物酶体起源的内共生假说进行严格的检验，我们将对来自大约20种不同细菌和几种具有代表性的真核生物的这四种蛋白质的基因进行测序和系统发育分析。此外，我们将对其他几个基因进行测序，例如编码热休克蛋白的基因，因为它们可以用于这个项目。在缺乏过氧化物酶体基因组的情况下，必须为尽可能多的不同过氧化物酶体蛋白质寻找一致的数据。如果过氧化物酶体蛋白的多个核基因都能追溯到细菌系统发育树上的同一位置，即与线粒体和质体不同的位置，那么“过氧化物酶体是内共生体吗？”这个问题的最有力答案就会出现。如果这样的答案即将到来，它将为重新评估残留的过氧化物异构体基因组可能仍然潜伏在某些真核生物中的可能性提供一个理由。该项目由环境生物学部（DEB）的系统和种群生物学项目以及分子和细胞生物科学学部（MCB）的代谢生物化学项目共同资助。过氧化物酶体是一种小细胞器，对细胞的代谢和有效功能起着非常重要的作用。一些致命的人类疾病可归因于过氧化物酶体功能缺陷。本研究将探讨这些重要细胞器的起源。＊＊＊

9318594 PALMER The peroxisome is a small, membrane-bound organelle found in the cells of all animals and other higher organisms. Peroxisomes lack a genome of their own, but a number of important biochemical reactions and enzymes (coded for by nuclear genes) occur within the peroxisome, and a large number of human diseases, mostly lethal, are caused by defects in peroxisomal function. Although much is known about the function of the peroxisome, we know nothing about its origin. This project seeks to remedy this situation by gathering evidence to test the two competing hypotheses for the origin of the peroxisome: 1) that it arose by internal compartmentation of a subset of metabolic enzymes, or 2) that, like chloroplasts and mitochondria, it arose endosymbiotically, i.e. by the permanent uptake of a bacterium (which turned into the peroxisome) by a primitive eukaryotic cell. In preliminary studies, we have identified four peroxisomal proteins that show provocatively high levels of similarity to bacterial homologs, and which thus provide suggestive evidence in support of hypothesis #2. To provide a rigorous test of the endosymbiotic hypothesis of peroxisomal origins, we will sequence and phylogenetically analyze the genes for each of these four proteins from about 20 diverse bacteria and from several representative eukaryotes. In addition, we will sequence several other genes, such as those encoding for the heat shock proteins, as they become available to this project. In the absence of a peroxisomal genome, it is imperative that congruent data be sought for as many different peroxisomal proteins as possible. The strongest answer to the question "Is the peroxisome an endosymbiont?" will come if multiple nuclear genes for peroxisomal proteins all trace back to the same place within a bacterial phylogenetic tree, a place distinct from that of both mitochondria and plastids. If such an answer is forthcoming, it would provide a rationale for reassessing the possibility that a residual perox isomal genome might still lurk in some eukaryotes. This project is being jointly funded by the Systematic and Population Biology programs of the Division of Environmental Biology (DEB) and the Metabolic Biochemistry program of the Division of Molecular and Cellular Biosciences (MCB). %%% Peroxisomes are small cellular organelles that are very important to the metabolism and effective functioning of cells. Several lethal human diseases are attributed to defects in peroxisomal functioning. This study will investigate the origin of these important organelles. ***