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. 2024 Apr 4;6(2):lqae032.
doi: 10.1093/nargab/lqae032. eCollection 2024 Jun.

Properties and predicted functions of large genes and proteins of apicomplexan parasites

Tiffany Fang  1 , Amir Mohseni  2 , Stefano Lonardi  2 , Choukri Ben Mamoun  1
Affiliations

Properties and predicted functions of large genes and proteins of apicomplexan parasites

Tiffany Fang et al. NAR Genom Bioinform. .

Abstract

Evolutionary constraints greatly favor compact genomes that efficiently encode proteins. However, several eukaryotic organisms, including apicomplexan parasites such as Toxoplasma gondii, Plasmodium falciparum and Babesia duncani, the causative agents of toxoplasmosis, malaria and babesiosis, respectively, encode very large proteins, exceeding 20 times their average protein size. Although these large proteins represent <1% of the total protein pool and are generally expressed at low levels, their persistence throughout evolution raises important questions about their functions and possible evolutionary pressures to maintain them. In this study, we examined the trends in gene and protein size, function and expression patterns within seven apicomplexan pathogens. Our analysis revealed that certain large proteins in apicomplexan parasites harbor domains potentially important for functions such as antigenic variation, erythrocyte invasion and immune evasion. However, these domains are not limited to or strictly conserved within large proteins. While some of these proteins are predicted to engage in conventional metabolic pathways within these parasites, others fulfill specialized functions for pathogen-host interactions, nutrient acquisition and overall survival.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
(A) Probability density function estimation of log size distribution of proteins in all genomes, smoothed with Gaussian kernel and compared with the ‘average eukaryotic protein size distribution’. (B) Genomic overview including genome size, GC content, number of CDSs, average protein length and number of large proteins normalized over genome size in Mb.
Figure 2.
Figure 2.
(A) Histogram showing distribution of protein size relative to number of total proteins in all parasite proteomes divided into size bins of 250 amino acids. (B) Distribution of protein size ratio over large proteins in all parasites.
Figure 3.
Figure 3.
GC content distribution by CDS length for whole genome and large genes of apicomplexan and outgroup species studied.
Figure 4.
Figure 4.
Log10-transformed scatterplots of TPM expression level by protein length across (A) the whole genome and (B) large proteins of each species, with trendlines for each.
Figure 5.
Figure 5.
Frequency of occurrence of significantly overrepresented (P < 0.001) GO classes in large proteins of all parasitic genomes and outgroups determined via hypergeometric distributions (GO annotation glossary is provided in Supplementary Table S3).
Figure 6.
Figure 6.
UpSet plots illustrating (A) the top 30 ortholog groupings of species in this study (top: total number of shared proteins among different organisms; bottom left: number of shared genes per organism) and (B) ortholog intersections in large proteins.
Figure 7.
Figure 7.
Top 10 most common conserved domains among large proteins of controls (A) S. cerevisiae and (B) E. histolytica as well as select Apicomplexa (C) T. gondii and (D) P. falciparum.
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