Genome organization and evolution of a eukaryotic nicotinate co-inducible pathway.

Eszter Bokor,Csaba Vágvölgyi,Zsuzsanna Hamari,Judit Ámon,Sándor Kocsubé,Michel Flipphi,Claudio Scazzocchio

doi:10.1098/rsob.210099

Abstract

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 organization of a possibly complete pathway of nicotinate utilization. In A. nidulans the regulon is organized in three distinct clusters, this organization is variable in the Ascomycota. In some Pezizomycotina species all 11 genes map in a single cluster; in others they map in two clusters. This variable organization sheds light on cluster evolution. Instances of gene duplication followed by or simultaneous with integration in the cluster, partial or total cluster loss, and 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.

Highlights

Nicotinic acid, a precursor of NAD and NADP, can be used by some bacteria as the sole nitrogen and carbon source
In order to search for additional genes involved in nicotinate metabolism, we investigated the cluster structure in available ascomycete genomes
In Cyphellophora europaea (Pezizomycotina, Eurotiomycetes, Chaetothyriales), five additional genes are positioned between hxnP and hxnR orthologues, forming a single, 11-gene cluster that includes all orthologues of the A. nidulans hxnZ, hxnY, hxnP, hxnR, hxnT and hxnS genes [11]

Summary

Introduction

Nicotinic acid (niacin, vitamin B3), a precursor of NAD and NADP, can be used by some bacteria as the sole nitrogen and carbon source. The common first step in all investigated prokaryotes is the hydroxylation of nicotinic acid (NA) to 6-hydroxynicotinic acid (6-NA). The detailed and variable further bacterial metabolic steps, whether aerobic or anaerobic, have been reviewed in [5]. A molybdenum cofactor (MOCO)-containing flavoprotein catalyses the conversion of NA to 6-NA ( purine hydroxylase II, previously called xanthine dehydrogenase II, HxnS [6,7,8,9]). The hxnS gene is a paralogue of hxA, encoding a canonical xanthine dehydrogenase (HxA, purine hydroxylase I [10,11]) the latter being co-regulated with most other genes of the purine utilization pathway ([12,13] and references therein). In A. nidulans an NA-inducible co-regulated gene cluster is extant (hxn1/VI cluster, for cluster 1 in chromosome VI) comprising six royalsocietypublishing.org/journal/rsob Open Biol. 11: 210099

Methods

Results

Conclusion