Genome-Wide Survey and Evolutionary Analysis of Trypsin Proteases in Apicomplexan Parasites

Abstract

Apicomplexa are an extremely diverse group of unicellular organisms that infect humans and other animals. Despite the great advances in combating infectious diseases over the past century, these parasites still have a tremendous social and economic burden on human societies, particularly in tropical and subtropical regions of the world. Proteases from apicomplexa have been characterized at the molecular and cellular levels, and central roles have been proposed for proteases in diverse processes. In this work, 16 new genes encoding for trypsin proteases are identified in 8 apicomplexan genomes by a genome-wide survey. Phylogenetic analysis suggests that these genes were gained through both intracellular gene transfer and vertical gene transfer. Identification, characterization and understanding of the evolutionary origin of protease-mediated processes are crucial to increase the knowledge and improve the strategies for the development of novel chemotherapeutic agents and vaccines.

Characterization of Toxoplasma DegP, a rhoptry serine protease crucial for lethal infection in mice

“…In addition, two PDZ domains are present in the C-terminal end of the protein. According to this modular architecture combining a protease domain with one or more C-terminal PDZ domains characteristic of Deg-like serine proteases, this protein was named Tg DegP [ 15 ]. Tg DegP harbors a predicted signal peptidase cleavage site after Ala30, indicative of trafficking along the secretory pathway.…”

“…Genome mining and multiple sequence alignment identified homologs of Tg DegP in most Apicomplexa, including Eimeria , Neospora , Hammondia , Babesia , Theileria and Plasmodium spp . with the notable exception of rodent malaria parasites [ 15 ]. Multiple copies of trypsin genes have been found in Toxoplasm a and Plasmodium .…”

“…Phylogenic analysis supports two different evolutionary origins for these trypsins. A group of apicomplexan trypsins clusters with plants, metazoan and cyanobacterial trypsins and contains Tg DegP (TGME49_262920), TGME49_290840 and Pf DegP (Pf_MAL8P1.12), the two copies in Toxoplasma arising probably by gene duplication [ 15 ]. Sequence alignment of Apicomplexa trypsins reveals the presence of a large insertion in the central region of Tg DegP, between the protease and PDZ domains ( S2A Fig ).…”

“…gondii . Tg DegP is a serine protease belonging to the HtrA (High Temperature Requirement A) or Deg-like family of serine proteases [ 15 ]. While DegP is dispensable for the lytic cycle of both RH type I and Pru type II strains, a marked decrease of acute virulence in Swiss mice is observed in DegP knock-out type II strain (KO- DegP II ).…”

Identification of Plasmodium vivax Proteins with Potential Role in Invasion Using Sequence Redundancy Reduction and Profile Hidden Markov Models

“…In the same year, Gaskell et al ., identified secreted enzymes in Toxoplasma gondii using SHARKhunt which used profile HMM based on the PRIAM polypeptide profile library to search for a set of genomic DNA sequences potentially encoding such proteins [12] . In 2010, Arena et al , identified 16 new genes encoding trypsin proteases in 8 Apicomplexan genomes [13] . Ghouila et al , constructed a system for identifying protein domains based on comparing HMM and Pfam profiles so that a Pfam family was represented by a multiple sequence alignment and a profile HMM [14] .…”