Alternaria Comparative Genomics: Expansion of Allergen Homologues in Clinically Relevant Saprophytes

The etiology of atopic or allergic asthma likely involves interactions between both human genetic factors and environmental stimuli. Alternaria is a ubiquitous fungus both outdoors and indoors, and is known for high rates of spore germination and antigen release in human airways and the environment. Allergic sensitization to Alternaria has been associated with asthma in various countries and in regions of the U.S., especially the SW. Furthermore, severe asthma and acute, sometimes life-threatening asthma attacks have been associated with Alternaria sensitivity or increased airborne concentrations of Alternaria spores. Interestingly, certain allergens, such as those from fungi may actually stimulate airway cells that are involved at the interface between innate and adaptive immunity. Recent studies show that fungal genomes harbor many known mold allergen homologues, including species specific and cross-reactive allergens. We have now sequenced the genomes of several important Alternaria spp., including the clinically relevant species, A. alternata and the plant pathogen, A. brassicicola and have used a comparative genomics approach to survey their pan-allergen repertoire. Our results show that fungal genomes in general contain many potential allergenic protein-encoding genes. Interestingly, in addition to mold allergen homologues, fungal genomes possess putative allergens from diverse sources such as pollen, insects, and venom to name a few. Interestingly, we found that A. alternata has the highest number (>280) of potential allergen encoding genes even when compared to the allergenic mold, Aspergillus fumigatus. The results of these studies and others related to Alternaria comparative genomics will be discussed.