title: Complex patterns of gene fission in the eukaryotic folate biosynthesis pathway.
abstract: Shared derived genomic characters can be useful for polarizing phylogenetic relationships, for example, gene fusions have been used to identify deep-branching relationships in the eukaryotes. Here, we report the evolutionary analysis of a three-gene fusion of folB, folK, and folP, which encode enzymes that catalyze consecutive steps in de novo folate biosynthesis. The folK-folP fusion was found across the eukaryotes and a sparse collection of prokaryotes. This suggests an ancient derivation with a number of gene losses in the eukaryotes potentially as a consequence of adaptation to heterotrophic lifestyles. In contrast, the folB-folK-folP gene is specific to a mosaic collection of Amorphea taxa (a group encompassing: Amoebozoa, Apusomonadida, Breviatea, and Opisthokonta). Next, we investigated the stability of this character. We identified numerous gene losses and a total of nine gene fission events, either by break up of an open reading frame (four events identified) or loss of a component domain (five events identified). This indicates that this three gene fusion is highly labile. These data are consistent with a growing body of data indicating gene fission events occur at high relative rates. Accounting for these sources of homoplasy, our data suggest that the folB-folK-folP gene fusion was present in the last common ancestor of Amoebozoa and Opisthokonta but absent in the Metazoa including the human genome. Comparative genomic data of these genes provides an important resource for designing therapeutic strategies targeting the de novo folate biosynthesis pathway of a variety of eukaryotic pathogens such as Acanthamoeba castellanii.
authors.affiliation: Department of Life Sciences, Natural History Museum, London, United Kingdom.
authors.forename: Finlay
authors.initials: F
authors.lastname: Maguire
authors.affiliation: Infection and Microbiology Research Group, Institute of Biomedical and Environmental Health Research, School of Science, University of the West of Scotland, Paisley, Renfrewshire, United Kingdom.
authors.forename: Fiona L
authors.initials: FL
authors.lastname: Henriquez
authors.affiliation: Biosciences, University of Exeter, Geoffrey Pope Building, Exeter, United Kingdom.
authors.forename: Guy
authors.initials: G
authors.lastname: Leonard
authors.affiliation: Department of Life Sciences, Natural History Museum, London, United Kingdom Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
authors.affiliation: Department of Biological Sciences, Mississippi State University.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Brown
authors.affiliation: Biosciences, University of Exeter, Geoffrey Pope Building, Exeter, United Kingdom Canadian Institute for Advanced Research, CIFAR Program in Integrated Microbial Biodiversity t.a.richards@exeter.ac.uk.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Richards
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019143:Evolution, Molecular; D005492:Folic Acid / Q000096:biosynthesis*; D023281:Genomics; D006801:Humans; D015398:Signal Transduction
chemical_list: D005492:Folic Acid
keywords: Diaphoretickes; comparative genomics; phylogenetics; pterin biosynthesis