Comparative analysis of programmed cell death pathways in filamentous fungi

Natalie D Fedorova¹ , Jonathan H Badger¹ , Geoff D Robson² , Jennifer R Wortman¹ and William C Nierman¹^,3

¹The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA

²Faculty of Life Sciences, 1.800 Stopford Building, University of Manchester, Manchester M13 9PT, UK

³The George Washington University School of Medicine, Department of Biochemistry and Molecular Biology, 2300 Eye Street, NW Washington, DC 20837, USA

author email corresponding author email

BMC Genomics 2005, 6:177doi:10.1186/1471-2164-6-177


Published:	8 December 2005

Abstract

Background

Fungi can undergo autophagic- or apoptotic-type programmed cell death (PCD) on exposure to antifungal agents, developmental signals, and stress factors. Filamentous fungi can also exhibit a form of cell death called heterokaryon incompatibility (HI) triggered by fusion between two genetically incompatible individuals. With the availability of recently sequenced genomes of Aspergillus fumigatus and several related species, we were able to define putative components of fungi-specific death pathways and the ancestral core apoptotic machinery shared by all fungi and metazoa.

Results

Phylogenetic profiling of HI-associated proteins from four Aspergilli and seven other fungal species revealed lineage-specific protein families, orphan genes, and core genes conserved across all fungi and metazoa. The Aspergilli-specific domain architectures include NACHT family NTPases, which may function as key integrators of stress and nutrient availability signals. They are often found fused to putative effector domains such as Pfs, SesB/LipA, and a newly identified domain, HET-s/LopB. Many putative HI inducers and mediators are specific to filamentous fungi and not found in unicellular yeasts. In addition to their role in HI, several of them appear to be involved in regulation of cell cycle, development and sexual differentiation. Finally, the Aspergilli possess many putative downstream components of the mammalian apoptotic machinery including several proteins not found in the model yeast, Saccharomyces cerevisiae.

Conclusion

Our analysis identified more than 100 putative PCD associated genes in the Aspergilli, which may help expand the range of currently available treatments for aspergillosis and other invasive fungal diseases. The list includes species-specific protein families as well as conserved core components of the ancestral PCD machinery shared by fungi and metazoa.