Department of Genetics, University of Melbourne, Victoria, Australia.
Genome Biol Evol. 2013;5(7):1336-52. doi: 10.1093/gbe/evt077.
Gene context determines gene expression, with local chromosomal environment most influential. Comparative genomic analysis is often limited in scope to conserved or divergent gene and protein families, and fungi are well suited to this approach with low functional redundancy and relatively streamlined genomes. We show here that one aspect of gene context, the amount of potential upstream regulatory sequence maintained through evolution, is highly predictive of both molecular function and biological process in diverse fungi. Orthologs with large upstream intergenic regions (UIRs) are strongly enriched in information processing functions, such as signal transduction and sequence-specific DNA binding, and, in the genus Aspergillus, include the majority of experimentally studied, high-level developmental and metabolic transcriptional regulators. Many uncharacterized genes are also present in this class and, by implication, may be of similar importance. Large intergenic regions also share two novel sequence characteristics, currently of unknown significance: they are enriched for plus-strand polypyrimidine tracts and an information-rich, putative regulatory motif that was present in the last common ancestor of the Pezizomycotina. Systematic consideration of gene UIR in comparative genomics, particularly for poorly characterized species, could help reveal organisms' regulatory priorities.
基因背景决定基因表达，局部染色体环境的影响最大。比较基因组分析的范围通常局限于保守或分歧的基因和蛋白质家族，而真菌具有低功能冗余和相对简化的基因组，非常适合这种方法。我们在这里表明，基因背景的一个方面，即通过进化保留的潜在上游调控序列的数量，在不同的真菌中对分子功能和生物过程具有高度的预测性。具有较大上游基因间区（UIR）的直系同源物在信息处理功能中得到了强烈富集，如信号转导和序列特异性 DNA 结合，并且在曲霉属中，包括大多数经过实验研究的、高水平的发育和代谢转录调节剂。许多未被表征的基因也存在于这一类中，因此可以推测它们可能具有相似的重要性。大的基因间区还具有两个新的序列特征，目前其意义尚不清楚：它们富含正链多嘧啶序列和一个信息丰富的、假定的调控基序，该基序存在于 Pezizomycotina 的最后共同祖先中。在比较基因组学中系统地考虑基因 UIR，特别是对于特征不明显的物种，可以帮助揭示生物体的调控优先级。
