Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster

<p>Abstract</p> <p>Background</p> <p>The biosynthesis of aflatoxin (AF) involves over 20 enzymatic reactions in a complex polyketide pathway that converts acetate and malonate to the intermediates sterigmatocystin (ST) and <it>O</it>-methylsterigmatocystin (OMST), the respective penultimate and ultimate precursors of AF. Although these precursors are chemically and structurally very similar, their accumulation differs at the species level for Aspergilli. Notable examples are <it>A</it>. <it>nidulans </it>that synthesizes only ST, <it>A</it>. <it>flavus </it>that makes predominantly AF, and <it>A</it>. <it>parasiticus </it>that generally produces either AF or OMST. Whether these differences are important in the evolutionary/ecological processes of species adaptation and diversification is unknown. Equally unknown are the specific genomic mechanisms responsible for ordering and clustering of genes in the AF pathway of <it>Aspergillus</it>.</p> <p>Results</p> <p>To elucidate the mechanisms that have driven formation of these clusters, we performed systematic searches of aflatoxin cluster homologs across five <it>Aspergillus </it>genomes. We found a high level of gene duplication and identified seven modules consisting of highly correlated gene pairs (<it>aflA/aflB, aflR/aflS, aflX/aflY</it>, <it>aflF/aflE, aflT/aflQ</it>, <it>aflC/aflW</it>, and <it>aflG/aflL</it>). With the exception of <it>A. nomius</it>, contrasts of mean <it>Ka/Ks </it>values across all cluster genes showed significant differences in selective pressure between section <it>Flavi </it>and non-section <it>Flavi </it>species. <it>A. nomius </it>mean <it>Ka/Ks </it>values were more similar to partial clusters in <it>A. fumigatus </it>and <it>A. terreus</it>. Overall, mean <it>Ka/Ks </it>values were significantly higher for section <it>Flavi </it>than for non-section <it>Flavi </it>species.</p> <p>Conclusion</p> <p>Our results implicate several genomic mechanisms in the evolution of ST, OMST and AF cluster genes. Gene modules may arise from duplications of a single gene, whereby the function of the pre-duplication gene is retained in the copy (<it>aflF</it>/<it>aflE</it>) or the copies may partition the ancestral function (<it>aflA/aflB</it>). In some gene modules, the duplicated copy may simply augment/supplement a specific pathway function (<it>aflR/aflS </it>and <it>aflX/aflY</it>) or the duplicated copy may evolve a completely new function (<it>aflT/aflQ </it>and <it>aflC/aflW</it>). Gene modules that are contiguous in one species and noncontiguous in others point to possible rearrangements of cluster genes in the evolution of these species. Significantly higher mean <it>Ka/Ks </it>values in section <it>Flavi </it>compared to non-section <it>Flavi </it>species indicate increased positive selection acting in the evolution of genes in OMST and AF gene clusters.</p

Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster-1

<p><b>Copyright information:</b></p><p>Taken from "Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster"</p><p>http://www.biomedcentral.com/1471-2148/7/111</p><p>BMC Evolutionary Biology 2007;7():111-111.</p><p>Published online 9 Jul 2007</p><p>PMCID:PMC1949824.</p><p></p>tion of genes in ST, AF and partial gene clusters. To simplify comparisons among AF and ST clusters we adopt the new AF gene nomenclature throughout [17]. The seven inferred gene modules are color coded. The arrows in the cluster at the top indicate the location of noncontiguous recombination blocks in the gene cluster [40]. The intergenic regions indicated by the black arrows share a common evolutionary history and can be concatenated into a single contiguous block such that and are adjacent in a hypothetical ancestor. Similarly the intergenic regions shown with grey arrows can be reunited such that and are adjacent. Overall this reorganization mirrors the order of these genes in the ST cluster and highlights the importance of gene module reorganization in the evolution of AF and ST clusters. A partial cluster duplication has been reported for some strains of [71]. Syntenic partial clusters of five genes (and ) were identified in and

Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster-0

<p><b>Copyright information:</b></p><p>Taken from "Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster"</p><p>http://www.biomedcentral.com/1471-2148/7/111</p><p>BMC Evolutionary Biology 2007;7():111-111.</p><p>Published online 9 Jul 2007</p><p>PMCID:PMC1949824.</p><p></p>y-axis across five genomes. The gene order in the histogram follows the order of genes in the cluster (see cluster schematic below histogram). . Hierarchical cluster dendrogram showing the correlations among gene duplicates in Figure 2A. Correlations are based on a dissimilarity measure of (1-) in which correlation values are assigned "distance" values ranging from 0.0 (completely correlated, = 1) to 1.0 (completely uncorrelated, = 0). The y-axis represents the height or distance between the gene groups divided at that point. The dendrogram shows seven putative gene modules listed from left to right as: and that are highly correlated (0.8

Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster-4

<p><b>Copyright information:</b></p><p>Taken from "Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster"</p><p>http://www.biomedcentral.com/1471-2148/7/111</p><p>BMC Evolutionary Biology 2007;7():111-111.</p><p>Published online 9 Jul 2007</p><p>PMCID:PMC1949824.</p><p></p>tion of genes in ST, AF and partial gene clusters. To simplify comparisons among AF and ST clusters we adopt the new AF gene nomenclature throughout [17]. The seven inferred gene modules are color coded. The arrows in the cluster at the top indicate the location of noncontiguous recombination blocks in the gene cluster [40]. The intergenic regions indicated by the black arrows share a common evolutionary history and can be concatenated into a single contiguous block such that and are adjacent in a hypothetical ancestor. Similarly the intergenic regions shown with grey arrows can be reunited such that and are adjacent. Overall this reorganization mirrors the order of these genes in the ST cluster and highlights the importance of gene module reorganization in the evolution of AF and ST clusters. A partial cluster duplication has been reported for some strains of [71]. Syntenic partial clusters of five genes (and ) were identified in and

Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster-2

<p><b>Copyright information:</b></p><p>Taken from "Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster"</p><p>http://www.biomedcentral.com/1471-2148/7/111</p><p>BMC Evolutionary Biology 2007;7():111-111.</p><p>Published online 9 Jul 2007</p><p>PMCID:PMC1949824.</p><p></p>ial clusters in and . Mean values for each gene are based on all pairwise comparisons with each species designated separately as the reference sequence

Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster-3

<p><b>Copyright information:</b></p><p>Taken from "Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster"</p><p>http://www.biomedcentral.com/1471-2148/7/111</p><p>BMC Evolutionary Biology 2007;7():111-111.</p><p>Published online 9 Jul 2007</p><p>PMCID:PMC1949824.</p><p></p>y-axis across five genomes. The gene order in the histogram follows the order of genes in the cluster (see cluster schematic below histogram). . Hierarchical cluster dendrogram showing the correlations among gene duplicates in Figure 2A. Correlations are based on a dissimilarity measure of (1-) in which correlation values are assigned "distance" values ranging from 0.0 (completely correlated, = 1) to 1.0 (completely uncorrelated, = 0). The y-axis represents the height or distance between the gene groups divided at that point. The dendrogram shows seven putative gene modules listed from left to right as: and that are highly correlated (0.8