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

In Aspergillus nidulans a regulon including 11 hxn genes (hxnS, T, R, P, Y, Z, X, W, V, M and N) is inducible by a nicotinate metabolic derivative, repressible by ammonium and under stringent control of the nitrogen-state sensitive GATA factor AreA and the specific transcription factor HxnR. This is the first report in a eukaryote of the genomic organisation of a possibly complete pathway of nicotinate utilisation. 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 map 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 a comprehensive phylogeny of six members of the cluster across representatives of all Ascomycota classes.