The mammalian PYHIN gene family: Phylogeny, evolution and expression

Abstract

Background: Proteins of the mammalian PYHIN (IFI200/HIN-200) family are involved in defence against infectionthrough recognition of foreign DNA. The family member absent in melanoma 2 (AIM2) binds cytosolic DNA via itsHIN domain and initiates inflammasome formation via its pyrin domain. AIM2 lies within a cluster of related genes,many of which are uncharacterised in mouse. To better understand the evolution, orthology and function of thesegenes, we have documented the range of PYHIN genes present in representative mammalian species, andundertaken phylogenetic and expression analyses.Results: No PYHIN genes are evident in non-mammals or monotremes, with a single member found in each ofthree marsupial genomes. Placental mammals show variable family expansions, from one gene in cow to four inhuman and 14 in mouse. A single HIN domain appears to have evolved in the common ancestor of marsupials andplacental mammals, and duplicated to give rise to three distinct forms (HIN-A, -B and -C) in the placental mammalancestor. Phylogenetic analyses showed that AIM2 HIN-C and pyrin domains clearly diverge from the rest of thefamily, and it is the only PYHIN protein with orthology across many species. Interestingly, although AIM2 isimportant in defence against some bacteria and viruses in mice, AIM2 is a pseudogene in cow, sheep, llama,dolphin, dog and elephant. The other 13 mouse genes have arisen by duplication and rearrangement within thelineage, which has allowed some diversification in expression patterns.Conclusions: The role of AIM2 in forming the inflammasome is relatively well understood, but molecularinteractions of other PYHIN proteins involved in defence against foreign DNA remain to be defined. The non-AIM2PYHIN protein sequences are very distinct from AIM2, suggesting they vary in effector mechanism in response toforeign DNA, and may bind different DNA structures. The PYHIN family has highly varied gene compositionbetween mammalian species due to lineage-specific duplication and loss, which probably indicates differentadaptations for fighting infectious disease. Non-genomic DNA can indicate infection, or a mutagenic threat. Wehypothesise that defence of the genome against endogenous retroelements has been an additional evolutionarydriver for PYHIN proteins. © 2012 Cridland et al.; licensee BioMed Central Ltd.