Birth and death of CYLD paralogues in vertebrates

Abstract

CYLD is a tumour suppressor Ubiquitin Specific Protease (USP), having characteristic peptidase C19 domain with unique and repetitive CAP-GLY domain. Our preliminary analyses have shown that CYLD has much higher number of paralogues in different vertebrate lineages compared to other USPs. This study aims to explore the expansion and death of CYLD paralogues in different vertebrate classes. In summary, phylogenetic tree was reconstructed on the basis of C19 domains of all CYLD homologues found by genome specific BLAST in selected species, covering major taxonomic orders of vertebrate classes. The tree was then aligned with the genomic synteny of the CYLD homologues and structural models of C19 domain of CYLD paralogues were also compared by Cα back bone superimposition. Genome mining data showed variable distribution of CYLD paralogues among different vertebrate lineages with up to six paralogues were found in Salmo salar and only one was found in all mammalian species. Phylogenetic tree revealed existence of variably populated five major paralogues of CYLD with very few incidences of species specific expansion. Alignment of the tree with the genomic synteny suggests that expansion of the paralogues is mainly contributed by whole genome duplication events at the root of all vertebrates and those proposed to happen specifically in fish lineages. Structural comparison of models points that all CYLD paralogues are catalytically active. To further explore functional redundancy, expressional studies of CYLD paralogues are required in representatives of different vertebrate lineages.