Scott Kroken

Assistant Professor

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Research Interests

Most recent evolutionary studies look for the pattern of evolution through phylogenetic and population genetic studies, using selectively neutral molecular markers. The results of these studies have been used to infer the processes of evolution, such as adaptation and diversification. As we come to understand which genes direct which processes in an organism, we can begin to study how these genes adapt an organism to its environment, and how these functions vary among different lineages. The goal of my research program is to investigate fungal species for these types of genetic changes that can result in key phenotypic changes. My approaches include: 1) determining the origins and population dynamics of virulent lineages of fungal pathogens in agriculture and medicine, 2) characterizing the evolution and inheritance of secondary metabolite genes and gene clusters, and the roles of their products in pathogen-host interactions, and 3) the use of comparative genomics and proteomics to identify differences among closely related fungi, and commonalities among distantly related fungi. Projects, both ongoing and in development, include: 1) Evolution of secondary metabolism in euascomycete fungi. Up to 5% of the genomes of euascomycete fungi are occupied by gene clusters that encode biochemical pathways for a diversity of polyketides, nonribosomal peptides, alkaloids, terpenoids, and combinations of these building blocks, to produce an array of mycotoxins that poison animals (e.g penicillin, lovastatin, fumonisin), phytotoxins that act as pathogenicty factors on plants (e.g T-toxin, AAL-toxin, HC-toxin), and antibacterials that deter their bacterial competitors (e.g. penicillin). Genomic comparisons show that all euascomycete fungi, regardless of nutritional mode (plant or animal pathogen, endophyte, or saprobe) share the same classes of secondary metabolite genes. Therefore, this genetic legacy has been used by diverging lineages of fungi for diverse biotic interactions as they evolved to occupy new niches. Among the questions I am trying to answer are: how does the expansion of gene families occur? What are the relative roles of gene loss cf. horizontal gene transfer? How do novel metabolic pathways form? Why do their constituent genes occur in gene clusters, whereas other functionally related genes are scattered throughout the genome of a eukaryotic organism? 2) Co-evolution of fungal pathogens with teosinte to maize. Agricultural epidemics occur when novel strains of fungi appear that are virulent on monocultures of plants. We usually have no idea of how these strains arose or where they came from. Hypotheses of mutation, recombination, or horizontal gene transfer of a virulence factor are proposed to explain the former question. The latter question is usually addressed by invoking host jumps from surrounding plants (e.g. weeds) that may be closely or distantly related, or by long-distance dispersal from distant populations. As a model system, I plan to investigate the fungi that occur on wild population of teosinte in Mexico and compare them to those that are found on cultivated populations of maize. Two speices of Fusarium that are significant pathogens of maize have already been found on teosinte. These and other fungi may serve as models for the co-evolution of fungus and host, in terms of pathogenicity and virulence factors, which may include secondary metabolites, and in terms of their population genetics, which may feature broader genetic diversity in the fungi in wild populations cf. agricultural populastions and thus exist as reservoirs for novel virulent strains. 3) Evolution of pathogenicity factors and conditionally dispensable chromosomes in the plant pathogen Nectria haematococca. This pathogen of pea contains an enzyme (pisatin demethylase) that detoxifies the phytoalexin (pisatin), which is produced to deter fungal infections. Only strains of this fungus that have this ability can colonize pea and cause significant disease. This gene resides on a small chromosome that can be lost, with the only evident phenotypic change being the loss of the ability to be a pathogen of pea. We are investigating the origin of pisitin demethylase, which is a P450 cytochrome, and thus a member of a huge gene superfamily. A gene genealogical approach will indicate when this gene diverged and evolved the ability to detoxify pisatin, and whether the known orthologs of this gene found in polyphyletic pathogens of pea were inherited vertically from a common ancestor, or gained by horizontal gene transfer in a common infection court. We are also investigating the structure and inferring the origin of the conditionally dispensable chromosome, which is part of the larger project to sequence the genome of this fungus. This project is a collaboration with Hans Van Etten. 4) Population genetics of Coccidioides posadasii, cause of Valley Fever in Arizona. Valley Fever is the most common nonsexally transmitted disease in Arizona. We are investigating the fungus that causes this disease, in order to determine if this species is structured by geography (is gene flow limited within Arizona?) by site (is clonality important? do rodents play a role in the patchy distribution of Coccidioides in soil?), by host (are humans, dogs, rodents and other species all susceptible to the same strains?). This information will be useful to understanding the epidemiology and pathology of this disease, and may help design strategies to reduce the incidence of this disease. This project is a collaboration with John Galgiani (VA) and Marc Orbach. This product will be the basis of graduate student Bridget Barker's Ph.D. dissertation. 5) Comparative proteomics of euascomcyete fungi in response to their symbiotic hosts (Bio5 initiative) We are looking for secreted factors in common to euascomycete fungi that interact with a range of host organisms, in order to understand how these fungi evolved so many different tropisms from an ancestral shared genome. The ultimate goal is making use of these common features as targets against pathogenic fungi. The fungus/host systems we are using include: the animal pathogen Coccidioides posadasii on mouse (John Galgiani), the opportunistic animal pathgen Aspergillus flavus on mouse (Peter Cotty), the animal allergen Alternaria sp. on mouse (Barry Pryor), the plant pathogen Magnaporthe grisea on rice (Marc Orbach), the plant pathogen Nectria haematococca MPVI on pea (Hans Van Etten), the endophyte Xylaria sp. on poplar (Betsy Arnold), and the lichenized fungus Cladonia grayi with unicellular green algae (Scott Kroken).

Selected Publications

Baker SE, Kroken S, Inderbitzin P, Asvarak T, Li BY, Shi L, Yoder OC, Turgeon BG. Feb 2006. Two polyketide synthase-encoding genes are required for biosynthesis of the polyketide virulence factor, T-toxin, by Cochliobolus heterostrophus. Mol Plant Microbe Interact, 19:139-49

Mandel MA Galgiani JN Kroken S Orbach MJ. Nov 2006. Coccidioides posadasii contains single chitin synthase genes corresponding to classes I to VII. Fungal Genet Biol, 43:775-88

Lee BN, Kroken S, Chou DY, Robbertse B, Yoder OC, Turgeon BG. Mar 2005. Functional analysis of all nonribosomal peptide synthetases in Cochliobolus heterostrophus reveals a factor, NPS6, involved in virulence and resistance to oxidative stress. Eukaryot Cell, 4:545-55

Kroken S, Glass NL, Taylor JW, Yoder OC, Turgeon BG. Dec 2003. Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes.. Proc Natl Acad Sci U S A, 100(26):15670-15675