Kondrashov Fyodor A, Koonin Eugene V, Morgunov Igor G, Finogenova Tatiana V, Kondrashova Marie N
Section on Ecology, Behavior and Evolution, Division of Biological Sciences, University of California at San Diego, 2218 Muir Biology Building, La Jolla, CA 92093, USA.
Biol Direct. 2006 Oct 23;1:31. doi: 10.1186/1745-6150-1-31.
The glyoxylate cycle is thought to be present in bacteria, protists, plants, fungi, and nematodes, but not in other Metazoa. However, activity of the glyoxylate cycle enzymes, malate synthase (MS) and isocitrate lyase (ICL), in animal tissues has been reported. In order to clarify the status of the MS and ICL genes in animals and get an insight into their evolution, we undertook a comparative-genomic study.
Using sequence similarity searches, we identified MS genes in arthropods, echinoderms, and vertebrates, including platypus and opossum, but not in the numerous sequenced genomes of placental mammals. The regions of the placental mammals' genomes expected to code for malate synthase, as determined by comparison of the gene orders in vertebrate genomes, show clear similarity to the opossum MS sequence but contain stop codons, indicating that the MS gene became a pseudogene in placental mammals. By contrast, the ICL gene is undetectable in animals other than the nematodes that possess a bifunctional, fused ICL-MS gene. Examination of phylogenetic trees of MS and ICL suggests multiple horizontal gene transfer events that probably went in both directions between several bacterial and eukaryotic lineages. The strongest evidence was obtained for the acquisition of the bifunctional ICL-MS gene from an as yet unknown bacterial source with the corresponding operonic organization by the common ancestor of the nematodes.
The distribution of the MS and ICL genes in animals suggests that either they encode alternative enzymes of the glyoxylate cycle that are not orthologous to the known MS and ICL or the animal MS acquired a new function that remains to be characterized. Regardless of the ultimate solution to this conundrum, the genes for the glyoxylate cycle enzymes present a remarkable variety of evolutionary events including unusual horizontal gene transfer from bacteria to animals.
乙醛酸循环被认为存在于细菌、原生生物、植物、真菌和线虫中，但在其他后生动物中不存在。然而，已有报道称动物组织中存在乙醛酸循环酶——苹果酸合酶（MS）和异柠檬酸裂解酶（ICL）的活性。为了阐明动物中MS和ICL基因的状况并深入了解它们的进化，我们进行了一项比较基因组研究。
通过序列相似性搜索，我们在节肢动物、棘皮动物和脊椎动物（包括鸭嘴兽和负鼠）中鉴定出了MS基因，但在众多已测序的胎盘哺乳动物基因组中未发现。通过比较脊椎动物基因组中的基因顺序确定的胎盘哺乳动物基因组中预期编码苹果酸合酶的区域，与负鼠MS序列具有明显的相似性，但包含终止密码子，这表明MS基因在胎盘哺乳动物中成为了假基因。相比之下，除了拥有双功能融合ICL-MS基因的线虫外，在其他动物中未检测到ICL基因。对MS和ICL系统发育树的研究表明，在几个细菌和真核生物谱系之间可能发生了多个双向的水平基因转移事件。获得的最有力证据是线虫的共同祖先从一个未知细菌来源获得了具有相应操纵子结构的双功能ICL-MS基因。
MS和ICL基因在动物中的分布表明，要么它们编码的是乙醛酸循环的替代酶，与已知的MS和ICL不是直系同源的，要么动物MS获得了一个有待表征的新功能。无论这个难题的最终解决方案是什么，乙醛酸循环酶的基因都呈现出各种各样的进化事件，包括从细菌到动物的不寻常水平基因转移。
