Effector variation at tandem gene arrays in tissue-dwelling coccidia: who needs antigenic variation anyway?

Abstract

Locus expansion and diversification is pervasive in apicomplexan genomes and is predominantly found in loci encoding secreted proteins that interact with factors outside of the parasite. Key for understanding the impact of each of these loci on the host requires identification and functional characterization of their protein products, but these repetitive loci often are refractory to genome assembly. In this review we focus on Toxoplasma gondii and its nearest relatives to highlight the known impact of duplicated and diversified loci on our understanding of the host-pathogen molecular arms race. We describe current tools used for the identification and characterization of these loci, and review the most recent examples of how gene-expansion driven diversification can lead to novel gene functions.

Figure 1:

Our model for the stepwise evolution of the MAF1 locus in T. gondii and its close relatives, N. caninum and H. hammondi. The MAF1a and MAF1b crystal structures ([11]) are in blue and orange, respectively. MAF1 maintains a vestigial ADPr binding macrodomain while duplication, expansion and GEDD events give rise to the neofunctionalized version of MAF1b driven at least in part by mutations of highly charged residues in the MAF1 C-terminus. Each significant change to the locus is marked and numbers correspond to MAF1 protein products in the key. MAF1b paralogs undergo subsequent diversification events following step 3 leading to the diverse shades of orange/yellow in the final T. gondii MAF1 locus.

Figure 2:

a) Distribution of sequence gaps (black ticks) across all 14 T. gondii chromosomes and their co-localization with known tandem gene expansions (red blocks). Sequence gaps were identified by stretches of “N’s” in version 30 of the T. gondii ME49 genome assembly which was downloaded from ToxoDB.org. Known tandem gene expansions were taken from the supplementary table in Adomako-Ankomah et al., mBio, 2014. b) Histogram of the location of sequence gaps in the T. gondii ME49 genome assembly (v30; www.toxodb.org) with respect to the nearest chromosome end, restricted to those on the 5 longest chromosomes (XII, XI, X, IX and VIII).