Evolutionary Origins of the Fumonisin Secondary Metabolite Gene Cluster in Fusarium verticillioides and Aspergillus niger

The secondary metabolite gene clusters of euascomycete fungi are among the largest known clusters of functionally related genes in eukaryotes. Most of these clusters are species specific or genus specific, and little is known about how they are formed during evolution. We used a comparative genomics approach to study the evolutionary origins of a secondary metabolite cluster that synthesizes a polyketide derivative, namely, the fumonisin (FUM) cluster of Fusarium verticillioides, and that of Aspergillus niger another fumonisin (fumonisin B) producing species. We identified homologs in other euascomycetes of the Fusarium verticillioides FUM genes and their flanking genes. We discuss four models for the origin of the FUM cluster in Fusarium verticillioides and argue that two of these are plausible: (i) assembly by relocation of initially scattered genes in a recent Fusarium verticillioides; or (ii) horizontal transfer of the FUM cluster from a distantly related Sordariomycete species. We also propose that the FUM cluster was horizontally transferred into Aspergillus niger, most probably from a Sordariomycete species

Visualizing syntenic relationships among the hemiascomycetes with the Yeast Gene Order Browser

The Yeast Gene Order Browser (YGOB) is an online tool designed to facilitate the comparative genomic visualization and appraisal of synteny within and between the genomes of seven hemiascomycete yeast species. Three of these genomes are polyploid, and hence contain intra-genomic syntenic regions, the correct assembly of which is a particular success of YGOB. Designed to accurately assemble, display and score gene order relationships, YGOB is both an interactive tool for browsing genomic data, and a software engine now being used for evolutionary analyses on a whole-genome scale. Underlying the online interface is the YGOB database, which consists of homology assignments across the species, extensively curated based on sequence similarity and novelly, an appraisal of genomic context (synteny) in multiple genomes. Currently the YGOB database incorporates genome data from Saccharomyces cerevisiae, Candida glabrata, Saccharomyces castellii, Ashbya gossypii, Kluyveromyces lactis, Kluyveromyces waltii and Saccharomyces kluyveri, but the system is scaleable to accommodate additional genomes. This paper discusses the usage and utility of version 1.0 of YGOB, which is publicly available at

Increased glycolytic flux as an outcome of whole-genome duplication in yeast

Correction to: Molecular Systems Biology 3:129. doi:10.1038/msb4100170; published online 31 July 200

Functional Partitioning of Yeast Co-Expression Networks after Genome Duplication

Several species of yeast, including the baker's yeast Saccharomyces cerevisiae, underwent a genome duplication roughly 100 million years ago. We analyze genetic networks whose members were involved in this duplication. Many networks show detectable redundancy and strong asymmetry in their interactions. For networks of co-expressed genes, we find evidence for network partitioning whereby the paralogs appear to have formed two relatively independent subnetworks from the ancestral network. We simulate the degeneration of networks after duplication and find that a model wherein the rate of interaction loss depends on the “neighborliness” of the interacting genes produces networks with parameters similar to those seen in the real partitioned networks. We propose that the rationalization of network structure through the loss of pair-wise gene interactions after genome duplication provides a mechanism for the creation of semi-independent daughter networks through the division of ancestral functions between these daughter networks

Additions, Losses, and Rearrangements on the Evolutionary Route from a Reconstructed Ancestor to the Modern Saccharomyces cerevisiae Genome

Comparative genomics can be used to infer the history of genomic rearrangements that occurred during the evolution of a species. We used the principle of parsimony, applied to aligned synteny blocks from 11 yeast species, to infer the gene content and gene order that existed in the genome of an extinct ancestral yeast about 100 Mya, immediately before it underwent whole-genome duplication (WGD). The reconstructed ancestral genome contains 4,703 ordered loci on eight chromosomes. The reconstruction is complete except for the subtelomeric regions. We then inferred the series of rearrangement steps that led from this ancestor to the current Saccharomyces cerevisiae genome; relative to the ancestral genome we observe 73 inversions, 66 reciprocal translocations, and five translocations involving telomeres. Some fragile chromosomal sites were reused as evolutionary breakpoints multiple times. We identified 124 genes that have been gained by S. cerevisiae in the time since the WGD, including one that is derived from a hAT family transposon, and 88 ancestral loci at which S. cerevisiae did not retain either of the gene copies that were formed by WGD. Sites of gene gain and evolutionary breakpoints both tend to be associated with tRNA genes and, to a lesser extent, with origins of replication. Many of the gained genes in S. cerevisiae have functions associated with ethanol production, growth in hypoxic environments, or the uptake of alternative nutrient sources

Mechanisms of Chromosome Number Evolution in Yeast

The whole-genome duplication (WGD) that occurred during yeast evolution changed the basal number of chromosomes from 8 to 16. However, the number of chromosomes in post-WGD species now ranges between 10 and 16, and the number in non-WGD species (Zygosaccharomyces, Kluyveromyces, Lachancea, and Ashbya) ranges between 6 and 8. To study the mechanism by which chromosome number changes, we traced the ancestry of centromeres and telomeres in each species. We observe only two mechanisms by which the number of chromosomes has decreased, as indicated by the loss of a centromere. The most frequent mechanism, seen 8 times, is telomere-to-telomere fusion between two chromosomes with the concomitant death of one centromere. The other mechanism, seen once, involves the breakage of a chromosome at its centromere, followed by the fusion of the two arms to the telomeres of two other chromosomes. The only mechanism by which chromosome number has increased in these species is WGD. Translocations and inversions have cycled telomere locations, internalizing some previously telomeric genes and creating novel telomeric locations. Comparison of centromere structures shows that the length of the CDEII region is variable between species but uniform within species. We trace the complete rearrangement history of the Lachancea kluyveri genome since its common ancestor with Saccharomyces and propose that its exceptionally low level of rearrangement is a consequence of the loss of the non-homologous end joining (NHEJ) DNA repair pathway in this species

Evidence for horizontal transfer of a secondary metabolite gene cluster between fungi

Background Filamentous fungi synthesize many secondary metabolites and are rich in genes encoding proteins involved in their biosynthesis. Genes from the same pathway are often clustered and co-expressed in particular conditions. Such secondary metabolism gene clusters evolve rapidly through multiple rearrangements, duplications and losses. It has long been suspected that clusters can be transferred horizontally between species, but few concrete examples have been described so far. Results In the rice blast fungus Magnaporthe grisea, the avirulence gene ACE1 that codes for a hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) belongs to a cluster of 15 genes involved in secondary metabolism. Additional related clusters were detected in the ascomycetes Chaetomium globosum, Stagonospora nodorum and Aspergillus clavatus. Gene-by-gene phylogenetic analysis showed that in C. globosum and M. grisea, the evolution of these ACE1-like clusters is characterized by successive complex duplication events including tandem duplication within the M. grisea cluster. The phylogenetic trees also present evidence that at least five of the six genes in the homologous ACE1 gene cluster in A. clavatus originated by horizontal transfer from a donor closely related to M. grisea. Conclusion The ACE1 cluster originally identified in M. grisea is shared by only few fungal species. Its sporadic distribution within euascomycetes is mainly explained by multiple events of duplication and losses. However, because A. clavatus contains an ACE1 cluster of only six genes, we propose that horizontal transfer from a relative of M. grisea into an ancestor of A. clavatus provides a much simpler explanation of the observed data than the alternative of multiple events of duplication and losses of parts of the cluster

Chromosomal G + C Content Evolution in Yeasts: Systematic Interspecies Differences, and GC-Poor Troughs at Centromeres

The G + C content at synonymous codon positions (GC3s) in genes varies along chromosomes in most eukaryotes. In Saccharomyces cerevisiae, regions of high GC3s are correlated with recombination hot spots, probably due to biased gene conversion. Here we examined how GC3s differs among groups of related yeast species in the Saccharomyces and Candida clades. The chromosomal locations of GC3s peaks and troughs are conserved among four Saccharomyces species, but we find that there have been highly consistent small shifts in their GC3s values. For instance, 84% of all S. cerevisiae genes have a lower GC3s value than their S. bayanus orthologs. There are extensive interspecies differences in the Candida clade both in the median value of GC3s (ranging from 22% to 49%) and in the variance of GC3s among genes. In three species—Candida lusitaniae, Pichia stipitis, and Yarrowia lipolytica—there is one region on each chromosome in which GC3s is markedly reduced. We propose that these GC-poor troughs indicate the positions of centromeres because in Y. lipolytica they coincide with the five experimentally identified centromeres. In P. stipitis, the troughs contain clusters of the retrotransposon Tps5. Likewise, in Debaryomyces hansenii, there is one cluster of the retrotransposon Tdh5 per chromosome, and all these clusters are located in GC-poor troughs. Locally reduced G + C content around centromeres is consistent with a model in which G + C content correlates with recombination rate, and recombination is suppressed around centromeres, although the troughs are unexpectedly wide (100–300 kb)

Evidence from comparative genomics for a complete sexual cycle in the 'asexual' pathogenic yeast Candida glabrata

BACKGROUND: Candida glabrata is a pathogenic yeast of increasing medical concern. It has been regarded as asexual since it was first described in 1917, yet phylogenetic analyses have revealed that it is more closely related to sexual yeasts than other Candida species. We show here that the C. glabrata genome contains many genes apparently involved in sexual reproduction. RESULTS: By genome survey sequencing, we find that genes involved in mating and meiosis are as numerous in C. glabrata as in the sexual species Kluyveromyces delphensis, which is its closest known relative. C. glabrata has a putative mating-type (MAT) locus and a pheromone gene (MFALPHA2), as well as orthologs of at least 31 other Saccharomyces cerevisiae genes that have no known roles apart from mating or meiosis, including FUS3, IME1 and SMK1. CONCLUSIONS: We infer that C. glabrata is likely to have an undiscovered sexual stage in its life cycle, similar to that recently proposed for C. albicans. The two Candida species represent two distantly related yeast lineages that have independently become both pathogenic and 'asexual'. Parallel evolution in the two lineages as they adopted mammalian hosts resulted in separate but analogous switches from overtly sexual to cryptically sexual life cycles, possibly in response to defense by the host immune system