Genome organisation and evolution of a eukaryotic nicotinate co-inducible pathway

We describe an HxnR-dependent regulon composed of 11 hxn genes (hxnS, T, R, P, Y, Z, X, W, V, M and N). The regulon is inducible by a nicotinate metabolic derivative and repressible by ammonium and under stringent control of the GATA factor AreA. This is the first publication of a eukaryotic, complete nicotinate metabolic cluster including five novel genes. While in A. nidulans the regulon is organised in three distinct clusters, this organisation is variable in the Ascomycota. In some Pezizomycotina species all the 11 genes are organised in a single cluster, in other in two clusters. This variable organisation sheds light on cluster evolution. Instances of gene duplication, followed by or simultaneous with integration in the cluster; partial or total cluster loss; horizontal gene transfer of several genes, including an example of whole cluster re-acquisition in Aspergillus of section Flavi were detected, together with the incorporation in some clusters of genes not found in the A. nidulans co-regulated regulon, which underlie both the plasticity and the reticulate character of metabolic cluster evolution. This study provides the first comprehensive protein sequence comparison of six members of the cluster across representatives of all Ascomycota classes, including several hundreds of species.