Gasch Audrey P, Moses Alan M, Chiang Derek Y, Fraser Hunter B, Berardini Mark, Eisen Michael B
Genome Sciences Department, Genomics Division, Lawrence Berkeley National Laboratory , Berkeley, California, USA.
PLoS Biol. 2004 Dec;2(12):e398. doi: 10.1371/journal.pbio.0020398. Epub 2004 Nov 9.
Relatively little is known about the mechanisms through which gene expression regulation evolves. To investigate this, we systematically explored the conservation of regulatory networks in fungi by examining the cis-regulatory elements that govern the expression of coregulated genes. We first identified groups of coregulated Saccharomyces cerevisiae genes enriched for genes with known upstream or downstream cis-regulatory sequences. Reasoning that many of these gene groups are coregulated in related species as well, we performed similar analyses on orthologs of coregulated S. cerevisiae genes in 13 other ascomycete species. We find that many species-specific gene groups are enriched for the same flanking regulatory sequences as those found in the orthologous gene groups fromS. cerevisiae, indicating that those regulatory systems have been conserved in multiple ascomycete species. In addition to these clear cases of regulatory conservation, we find examples of cis-element evolution that suggest multiple modes of regulatory diversification, including alterations in transcription factor-binding specificity, incorporation of new gene targets into an existing regulatory system, and cooption of regulatory systems to control a different set of genes. We investigated one example in greater detail by measuring the in vitro activity of the S. cerevisiae transcription factor Rpn4p and its orthologs from Candida albicans and Neurospora crassa. Our results suggest that the DNA binding specificity of these proteins has coevolved with the sequences found upstream of the Rpn4p target genes and suggest that Rpn4p has a different function in N. crassa.
关于基因表达调控进化的机制，我们了解得相对较少。为了研究这一点，我们通过检查调控共表达基因的顺式调控元件，系统地探索了真菌中调控网络的保守性。我们首先鉴定了共表达的酿酒酵母基因群体，这些基因群体富含具有已知上游或下游顺式调控序列的基因。由于我们推断这些基因群体中的许多在相关物种中也是共表达的，因此我们对其他13种子囊菌物种中共表达的酿酒酵母基因的直系同源基因进行了类似分析。我们发现，许多物种特异性基因群体与酿酒酵母直系同源基因群体中发现的侧翼调控序列相同，这表明这些调控系统在多个子囊菌物种中得以保守。除了这些明显的调控保守案例外，我们还发现了顺式元件进化的例子，这些例子表明了多种调控多样化模式，包括转录因子结合特异性的改变、将新的基因靶点纳入现有调控系统以及调控系统被用于控制不同的一组基因。我们通过测量酿酒酵母转录因子Rpn4p及其来自白色念珠菌和粗糙脉孢菌的直系同源基因的体外活性，更详细地研究了一个例子。我们的结果表明，这些蛋白质的DNA结合特异性已与Rpn4p靶基因上游发现的序列共同进化，并且表明Rpn4p在粗糙脉孢菌中具有不同的功能。
