Bioinformatics Analysis of Bacterial Annexins – Putative Ancestral Relatives of Eukaryotic Annexins

Abstract

Annexins are Ca2+-binding, membrane-interacting proteins, widespread among eukaryotes, consisting usually of four structurally similar repeated domains. It is accepted that vertebrate annexins derive from a double genome duplication event. It has been postulated that a single domain annexin, if found, might represent a molecule related to the hypothetical ancestral annexin. The recent discovery of a single-domain annexin in a bacterium, Cytophaga hutchinsonii, apparently confirmed this hypothesis. Here, we present a more complex picture. Using remote sequence similarity detection tools, a survey of bacterial genomes was performed in search of annexin-like proteins. In total, we identified about thirty annexin homologues, including single-domain and multi-domain annexins, in seventeen bacterial species. The thorough search yielded, besides the known annexin homologue from C. hutchinsonii, homologues from the Bacteroidetes/Chlorobi phylum, from Gemmatimonadetes, from beta- and delta-Proteobacteria, and from Actinobacteria. The sequences of bacterial annexins exhibited remote but statistically significant similarity to sequence profiles built of the eukaryotic ones. Some bacterial annexins are equipped with additional, different domains, for example those characteristic for toxins. The variation in bacterial annexin sequences, much wider than that observed in eukaryotes, and different domain architectures suggest that annexins found in bacteria may actually descend from an ancestral bacterial annexin, from which eukaryotic annexins also originate. The hypothesis of an ancient origin of bacterial annexins has to be reconciled with the fact that remarkably few bacterial strains possess annexin genes compared to the thousands of known bacterial genomes and with the patchy, anomalous phylogenetic distribution of bacterial annexins. Thus, a massive annexin gene loss in several bacterial lineages or very divergent evolution would appear a likely explanation. Alternative evolutionary scenarios, involving horizontal gene transfer between bacteria and protozoan eukaryotes, in either direction, appear much less likely. Altogether, current evidence does not allow unequivocal judgement as to the origin of bacterial annexins.

Ectopic overexpression of abiotic stress-induced rice annexin,OsAnn5potentiates tolerance to abiotic stresses

“…Annexins belong to a diverse multi-gene, multi-functional family of proteins (Moss et al, 2004;Clark et al, 2012, Yadav et al, 2018. They have been identified in fungi (Grenville-Briggs et al, 2010;Khalaj et al, 2015) plants, animals, aarchaea and also in prokaryotes (Kodavali et al, 2014). Annexin superfamily has been grouped into seven subfamilies, which are designated as ANNXA to ANNXG.…”

Structural and lipid-binding characterization of human annexin A13a reveals strong differences with its long A13b isoform

“…They are expressed by all living organisms, from protists to higher eukaryotes and plants, but with the exception of bacteria. However, the group of Fernandez and Morgan first reported the presence of a gene coding for a single domain annexin in the bacteria Cytophaga hutchinsonii, although the protein is not expressed (Morgan et al, 2006) and a broader survey of bacterial genomes has identified around 30 annexin homologs, including single-domain and multi-domain annexins in 17 bacterial species (Kodavali et al, 2014).…”

The enigmatic role of fungal annexins: the case of Cryptococcus neoformans

“…Administration of giardin to mice induced protective immunity against Giardia and is under investigation for its vaccine potential (8). The Burkholderia JOSHI_001 protein possesses both a colicinD toxin domain and an annexin domain (9), which reinforces the notion that microbial annexins contribute to microbial virulence.…”

“…A recent review revealed a paucity of studies about microbial annexins, but the available information suggests that these proteins are critical for the virulence of certain pathogens (8, 9). Giardin from Giardia (10) is an immunodominant annexin protein (11).…”