Fungal metabolic gene clusters—caravans traveling across genomes and environments

Abstract

Metabolic gene clusters (MGCs), physically co-localized genes participating in the same metabolic pathway, are signature features of fungal genomes. MGCs are most often observed in specialized metabolism, having evolved in individual fungal lineages in response to specific ecological needs, such as the utilization of uncommon nutrients (e.g., galactose and allantoin) or the production of secondary metabolic antimicrobial compounds and virulence factors (e.g., aflatoxin and melanin). A flurry of recent studies has shown that several MGCs, whose functions are often associated with fungal virulence as well as with the evolutionary arms race between fungi and their competitors, have experienced horizontal gene transfer (HGT). In this review, after briefly introducing HGT as a source of gene innovation, we examine the evidence for HGT's involvement on the evolution of MGCs and, more generally of fungal metabolism, enumerate the molecular mechanisms that mediate such transfers and the ecological circumstances that favor them, as well as discuss the types of evidence required for inferring the presence of HGT in MGCs. The currently available examples indicate that transfers of entire MGCs have taken place between closely related fungal species as well as distant ones and that they sometimes involve large chromosomal segments. These results suggest that the HGT-mediated acquisition of novel metabolism is an ongoing and successful ecological strategy for many fungal species.

Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants

“…In fungi, both gene duplication and horizontal transfer are more pronounced in clustered genes than in their nonclustered counterparts (Wisecaver et al, 2014). Furthermore, fungal clusters are often located near telomeres and transposable elements (Wisecaver and Rokas, 2015). In plants, it is well established that plant-specialized metabolic enzymes evolved from plant primary metabolic enzymes (Weng et al, 2012;Moghe and Last, 2015).…”

“…Several mechanisms have been proposed to lead to the formation of gene clusters in bacteria and fungi (Fondi et al, 2009;Wisecaver et al, 2014;Wisecaver and Rokas, 2015). LD of metabolic genes was enriched in clusters and could have played a role in metabolic gene cluster formation in plants (Supplemental Fig.…”

“…However, several theories have been proposed, including coevolution (Ehrlich and Raven, 1964), sequential evolution (Jermy, 1984), random screening (Jones and Firn, 1991), duplication and subfunctionalization of transcriptional regulators (Grotewold, 2005), and catalytic promiscuity and the radiation of specialized metabolic enzymes (Weng et al, 2012). In bacteria and fungi, which also produce a large array of specialized metabolites, many biosynthetic pathways are organized into physically colocalized metabolic gene clusters (Cimermancic et al, 2014;Wisecaver and Rokas, 2015). Plant metabolic pathways are generally not known to occur in clusters, although there are now about 20 reported cases of specialized metabolic pathways that occur as gene clusters (Boycheva et al, 2014;Nützmann and Osbourn, 2014;Nützmann et al, 2016).…”

The botrydial biosynthetic gene cluster of Botrytis cinerea displays a bipartite genomic structure and is positively regulated by the putative Zn(II)2Cys6 transcription factor BcBot6

“…All together, these data suggest that botryanes may be produced by phylogenetically distant fungi and that the BOT gene cluster was subjected to several genomic rearrangements. This cluster might originate from a common ancestor of Leotiomycetes and Sordariomycetes and might have been lost from the majority of species or, alternatively, the cluster may have been subjected to horizontal gene transfer between different species as demonstrated for several fungal SM gene clusters (Wisecaver and Rokas, 2015).…”

Horizontally acquired genes in early-diverging pathogenic fungi enable the use of host nucleosides and nucleotides

“…The importance and scale of HGT in eukaryotes, however, is a matter of debate (4)(5)(6)(7). In particular, HGT into fungi was thought to be rare, but several examples from bacteria into fungi or between fungi have recently been described (5,8,9). For example, one phylum of early-diverging fungi, the Microsporidia, has had a handful of HGT events documented (5,(10)(11)(12), but these fungi are thought to have acquired relatively few genes through HGT (13).…”