Schmitt Imke, Lumbsch H Thorsten
Department of Plant Biology and Bell Museum of Natural History, University of Minnesota, St Paul, MN, USA.
PLoS One. 2009;4(2):e4437. doi: 10.1371/journal.pone.0004437. Epub 2009 Feb 12.
Polyketides are natural products with a wide range of biological functions and pharmaceutical applications. Discovery and utilization of polyketides can be facilitated by understanding the evolutionary processes that gave rise to the biosynthetic machinery and the natural product potential of extant organisms. Gene duplication and subfunctionalization, as well as horizontal gene transfer are proposed mechanisms in the evolution of biosynthetic gene clusters. To explain the amount of homology in some polyketide synthases in unrelated organisms such as bacteria and fungi, interkingdom horizontal gene transfer has been evoked as the most likely evolutionary scenario. However, the origin of the genes and the direction of the transfer remained elusive.
METHODOLOGY/PRINCIPAL FINDINGS: We used comparative phylogenetics to infer the ancestor of a group of polyketide synthase genes involved in antibiotic and mycotoxin production. We aligned keto synthase domain sequences of all available fungal 6-methylsalicylic acid (6-MSA)-type PKSs and their closest bacterial relatives. To assess the role of symbiotic fungi in the evolution of this gene we generated 24 6-MSA synthase sequence tags from lichen-forming fungi. Our results support an ancient horizontal gene transfer event from an actinobacterial source into ascomycete fungi, followed by gene duplication.
CONCLUSIONS/SIGNIFICANCE: Given that actinobacteria are unrivaled producers of biologically active compounds, such as antibiotics, it appears particularly promising to study biosynthetic genes of actinobacterial origin in fungi. The large number of 6-MSA-type PKS sequences found in lichen-forming fungi leads us hypothesize that the evolution of typical lichen compounds, such as orsellinic acid derivatives, was facilitated by the gain of this bacterial polyketide synthase.
聚酮化合物是一类具有广泛生物学功能和药物应用的天然产物。通过了解导致生物合成机制产生的进化过程以及现存生物体的天然产物潜力，有助于聚酮化合物的发现和利用。基因复制和亚功能化以及水平基因转移被认为是生物合成基因簇进化的机制。为了解释细菌和真菌等不相关生物体中某些聚酮合酶的同源性，跨王国水平基因转移被认为是最可能的进化情况。然而，基因的起源和转移方向仍然难以捉摸。
方法/主要发现：我们使用比较系统发育学来推断一组参与抗生素和霉菌毒素产生的聚酮合酶基因的祖先。我们比对了所有可用的真菌6-甲基水杨酸（6-MSA）型聚酮合酶及其最接近的细菌亲属的酮合酶结构域序列。为了评估共生真菌在该基因进化中的作用，我们从地衣形成真菌中生成了24个6-MSA合酶序列标签。我们的结果支持了一个古老的水平基因转移事件，即从放线菌来源转移到子囊菌真菌中，随后发生基因复制。
结论/意义：鉴于放线菌是生物活性化合物（如抗生素）的无与伦比的生产者，研究真菌中放线菌来源的生物合成基因似乎特别有前景。在地衣形成真菌中发现的大量6-MSA型聚酮合酶序列使我们推测，典型地衣化合物（如苔色酸衍生物）的进化是由于获得了这种细菌聚酮合酶而促进的。
