Genomic clustering within functionally related gene families in Ascomycota fungi

Abstract

Multiple mechanisms collaborate for proper regulation of gene expression. One layer of this regulation is through the clustering of functionally related genes at discrete loci throughout the genome. This phenomenon occurs extensively throughout Ascomycota fungi and is an organizing principle for many gene families whose proteins participate in diverse molecular functions throughout the cell. Members of this phylum include organisms that serve as model systems and those of interest medically, pharmaceutically, and for industrial and biotechnological applications. In this review, we discuss the prevalence of functional clustering through a broad range of organisms within the phylum. Position effects on transcription, genomic locations of clusters, transcriptional regulation of clusters, and selective pressures contributing to the formation and maintenance of clusters are addressed, as are common methods to identify and characterize clusters.

Keywords: Ascomycota fungi; Biosynthetic gene clusters; Genomics; Metabolic gene clusters; Secondary metabolite gene clusters.

Fig. 1

Penicillium visualized by light microscopy. At lower power (A, 400× magnification) the ascocarp (a completely closed fruit body called a cleistothecium) is visible. At higher magnifications (B, 1000× magnification) the ascus is visible with the individual ascospores (three of the spores are highlighted with an arrow). Images courtesy of Kelley Healey.

Fig. 2

Genomic arrangement of representative functional clustered biosynthetic genes. (A) The six-gene cluster in A. fumigatus for conidial pigment synthesis, (B) the three-gene cluster in A. nidulans for biotin synthesis, and (C) the four-gene supercluster in C. militaris. Genomic loci are to approximate scale and each gene is connected to the enzyme that it produces. Data is a compilation from , ,

Fig. 3

Representative clustering arrangements observed in S. cerevisiae at three RRB paired loci. (A) The GCD10-NOP2 locus, (B) the RRP15-NOC4 locus, and (C) the RPF1-GAR1 locus are shown relative to the PAC and RRPE cis- regulatory promoter motifs shown in purple and red, respectively. All loci are to approximate scale, although the relative size of the promoter motifs has been exaggerated to highlight their location and arrangement. Image is . (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Functionally clustered genes localize to genomic loci that are more conducive to regulation at a distance. The pairwise Spearman’s correlation coefficient was determined for the nitrogen metabolism, ribosomal protein, and toxin response genes in S. cerevisiae as described . SCC versus genomic distance is plotted for (A) the non-clustered, singleton members of each set and (B) the clustered members of each set and the data was fit to a logarithmic decay. For clarity and ease of comparison, the decay curves are overlaid in (C).