Broad Institute, Cambridge, MA, USA.
BMC Genomics. 2010 Mar 26;11:208. doi: 10.1186/1471-2164-11-208.
Fusarium graminearum (Fg), a major fungal pathogen of cultivated cereals, is responsible for billions of dollars in agriculture losses. There is a growing interest in understanding the transcriptional regulation of this organism, especially the regulation of genes underlying its pathogenicity. The generation of whole genome sequence assemblies for Fg and three closely related Fusarium species provides a unique opportunity for such a study.
Applying comparative genomics approaches, we developed a computational pipeline to systematically discover evolutionarily conserved regulatory motifs in the promoter, downstream and the intronic regions of Fg genes, based on the multiple alignments of sequenced Fusarium genomes. Using this method, we discovered 73 candidate regulatory motifs in the promoter regions. Nearly 30% of these motifs are highly enriched in promoter regions of Fg genes that are associated with a specific functional category. Through comparison to Saccharomyces cerevisiae (Sc) and Schizosaccharomyces pombe (Sp), we observed conservation of transcription factors (TFs), their binding sites and the target genes regulated by these TFs related to pathways known to respond to stress conditions or phosphate metabolism. In addition, this study revealed 69 and 39 conserved motifs in the downstream regions and the intronic regions, respectively, of Fg genes. The top intronic motif is the splice donor site. For the downstream regions, we noticed an intriguing absence of the mammalian and Sc poly-adenylation signals among the list of conserved motifs.
This study provides the first comprehensive list of candidate regulatory motifs in Fg, and underscores the power of comparative genomics in revealing functional elements among related genomes. The conservation of regulatory pathways among the Fusarium genomes and the two yeast species reveals their functional significance, and provides new insights in their evolutionary importance among Ascomycete fungi.
禾谷镰刀菌（Fg）是一种主要的农作物真菌病原体，造成数十亿美元的农业损失。人们越来越感兴趣于理解该生物体的转录调控，尤其是与致病性相关的基因调控。禾谷镰刀菌及其三个密切相关的镰刀菌物种的全基因组序列组装为这样的研究提供了一个独特的机会。
应用比较基因组学方法，我们开发了一个计算管道，根据测序的镰刀菌基因组的多重比对，系统地发现禾谷镰刀菌基因启动子、下游和内含子区域中进化保守的调控基序。使用这种方法，我们在启动子区域发现了 73 个候选调控基序。这些基序中近 30%高度富集在与特定功能类别相关的禾谷镰刀菌基因的启动子区域。通过与酿酒酵母（Sc）和粗糙脉孢菌（Sp）进行比较，我们观察到与已知响应应激条件或磷酸盐代谢途径相关的转录因子（TFs）、它们的结合位点以及这些 TFs 调控的靶基因的保守。此外，这项研究还揭示了禾谷镰刀菌基因下游区域和内含子区域分别有 69 个和 39 个保守基序。内含子的顶级基序是剪接受体位点。对于下游区域，我们注意到在保守基序列表中缺少哺乳动物和 Sc 的多聚腺苷酸化信号。
这项研究提供了禾谷镰刀菌中第一个全面的候选调控基序列表，并强调了比较基因组学在揭示相关基因组中功能元件方面的强大功能。调控途径在镰刀菌基因组和两种酵母物种之间的保守揭示了它们的功能意义，并为它们在子囊菌真菌中的进化重要性提供了新的见解。
