title: Outgroup, alignment and modelling improvements indicate that two TNFSF13-like genes existed in the vertebrate ancestor.
abstract: The molecular machinery required for lymphocyte development and differentiation appears to have emerged concomitantly with distinct B- and T-like lymphocyte subsets in the ancestor of all vertebrates. The TNFSF superfamily (TNFSF) members BAFF (TNFSF13/Blys) and APRIL (TNFSF13) are key regulators of B cell development survival, and activation in mammals, but the temporal emergence of these molecules, and their precise relationship to the newly identified TNFSF gene BALM (BAFF and APRIL-like molecule), have not yet been elucidated. Here, to resolve the early evolutionary history of this family, we improved outgroup sampling and alignment quality, and applied better fitting substitution models compared to past studies. Our analyses reveal that BALM is a definitive TNFSF13 family member, which split from BAFF in the gnathostome (jawed vertebrate) ancestor. Most importantly, however, we show that both the APRIL and BAFF lineages existed in the ancestors of all extant vertebrates. This implies that APRIL has been lost, or is yet to be found, in cyclostomes (jawless vertebrates). Our results suggest that lineage-specific gene duplication and loss events have caused lymphocyte regulation, despite shared origins, to become secondarily distinct between gnathostomes and cyclostomes. Finally, the structure of lamprey BAFF-like, and its phylogenetic placement as sister to BAFF and BALM, but not the more slowly evolving APRIL, indicates that the primordial lymphocyte regulator was more APRIL-like than BAFF-like.
authors.affiliation: School of Biological Sciences, University of Aberdeen, Aberdeen, AB24 2TZ, UK.|Centre for Genome-Enabled Biology & Medicine, University of Aberdeen, Aberdeen, AB24 2TZ, UK.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Redmond
authors.affiliation: School of Biological Sciences, University of Aberdeen, Aberdeen, AB24 2TZ, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Pettinello
authors.affiliation: School of Biological Sciences, University of Aberdeen, Aberdeen, AB24 2TZ, UK. hdooley@som.umaryland.edu.|Dept. Microbiology & Immunology, Institute of Marine & Environmental Technology, University of Maryland School of Medicine, 701 E. Pratt Street, Baltimore, MD21202, USA. hdooley@som.umaryland.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Dooley
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000235:genetics*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics*; D019143:Evolution, Molecular; D010802:Phylogeny; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics*
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13
keywords: APRIL; BAFF; BALM; Phylogenetics; TNFSF13; Vertebrate evolution