α‐Proteobacterial Relationship of Apicomplexan Lactate and Malate Dehydrogenases

Abstract

We have cloned and sequenced a lactate dehydrogenase (LDH) gene from Cryptosporidium parvum (CpLDH1). With this addition, and that of four recently deposited alpha-proteobacterial malate dehydrogenase (MDH) genes, the phylogenetic relationships among apicomplexan LDH and bacterial MDH were re-examined. Consistent with previous studies, our maximum likelihood (ML) analysis using the quartet-puzzling method divided 105 LDH/MDH enzymes into five clades, and confirmed that mitochondrial MDH is a sister clade to those of y-proteobacteria, rather than to alpha-proteobacteria. In addition, a Cryptosporidium parvum MDH (CpMDH1) was identified from the ongoing Cryptosporidium genome project that appears to belong to a distinct clade (III) comprised of 22 sequences from one archaebacterium, numerous eubacteria, and several apicomplexans. Using the ML puzzling test and bootstrapping analysis with protein distance and parsimony methods, the resulting trees not only robustly confirmed the alpha-proteobacterial relationship of apicomplexan LDH/MDH, but also supported a monophyletic relationship of CpLDH1 with CpMDHI. These data suggest that, unlike most other eukaryotes, the Apicomplexa may be one of the few lineages retaining an alpha-proteobacterial-type MDH that could have been acquired from an ancestral alpha-proteobacterium through primary endosymbiosis giving rise to the mitochondria, or through an unknown lateral gene transfer (LGT) event.

An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases

“…A maximum likelihood phylogeny of representatives of all known LDH and MDH proteins provides strong support for five distinct protein clades (Figure 3A, Figure 3—figure supplement 1): canonical LDHs, ‘LDH-like’ MDHs, mitochondrial-like MDHs, cytosolic-like MDHs, and the poorly characterized HicDHs (hydroxyisocaproate-related dehydrogenases), confirming previous phylogenetic analyses (Golding and Dean, 1998; Madern, 2002; Zhu and Keithly, 2002; Madern et al, 2004). …”

“…A key event in the early evolution of the Apicomplexa was the acquisition of a malate dehydrogenase (MDH) via lateral gene transfer from α-proteobacteria (Golding and Dean, 1998; Madern, 2002; Zhu and Keithly, 2002). Following a gene duplication event roughly 700–900 Mya, one copy of this MDH evolved a novel substrate specificity to become a highly specific lactate dehydrogenase (LDH) that is now essential to the life cycle of many modern apicomplexans (Royer et al, 1986).…”

“…Apicomplexan LDH evolved from the duplication of an ancestral MDH gene (Golding and Dean, 1998; Zhu and Keithly, 2002). Gene duplication is widely considered the major force that has driven the evolutionary diversity of protein functions (Innan and Kondrashov, 2010).…”

Jumbled Genomes: Missing Apicomplexan Synteny

“…1) relative to many sequenced eukaryotes (Carlton et al 2002, 2008; Gardner et al 2002, 2005; Abrahamsen et al 2004; Brayton et al 2007). They are characterized by gene loss (Kuo and Kissinger 2008), with only a few thousand protein-encoding genes per genome and both intracellular and lateral gene transfer (Zhu and Keithly 2002; Huang, Mullapudi, Lancto, et al 2004; Huang, Mullapudi, Sicheritz-Ponten, and Kissinger 2004; Striepen et al 2004; Huang and Kissinger 2006; Nagamune and Sibley 2006). The most striking example of gene loss to date is found in Cryptosporidium parvum , where all pathways for de novo nucleotide synthesis have been lost and nucleotide salvage pathways have been acquired (Striepen et al 2004).…”

Mitosomes of Entamoeba histolytica are abundant mitochondrion-related remnant organelles that lack a detectable organellar genome

“…Some, such as those of Entamoeba and Cryptosporidium, have been shown to contain chaperonin Cpn60, a protein known to participate in the refolding of imported proteins (Sigler et al, 1998; Mai et al, 1999;Tovar et al, 1999;Riordan et al, 2003); mitosomes of Trachipleistophora contain a mitochondrialtype Hsp70 (mtHsp70), a molecular motor that helps internalize proteins into the organelle (Matouschek et al, 2000;Williams et al, 2002). Other proteins have also been suggested as putative mitosomal components in various amitochondrial lineages but their cellular localization has not been demonstrated experimentally (Clark & Roger, 1995;Bakatselou et al, 2000Bakatselou et al, , 2003Katinka et al, 2001;Morrison et al, 2001;Zhu & Keithly, 2002;Arisue et al, 2002). Perhaps the most significant finding in relation to the biology of mitosomes is the direct demonstration that Giardia mitosomes function in the biosynthesis of molecular iron-sulphur (Fe-S) clusters and in their subsequent incorporation into functional Fe-S proteins (Tovar et al, 2003).…”