The Elusive Mitochondrial Genomes of Apicomplexa: Where Are We Now?

Abstract

Mitochondria are vital organelles of eukaryotic cells, participating in key metabolic pathways such as cellular respiration, thermogenesis, maintenance of cellular redox potential, calcium homeostasis, cell signaling, and cell death. The phylum Apicomplexa is entirely composed of obligate intracellular parasites, causing a plethora of severe diseases in humans, wild and domestic animals. These pathogens include the causative agents of malaria, cryptosporidiosis, neosporosis, East Coast fever and toxoplasmosis, among others. The mitochondria in Apicomplexa has been put forward as a promising source of undiscovered drug targets, and it has been validated as the target of atovaquone, a drug currently used in the clinic to counter malaria. Apicomplexans present a single tubular mitochondria that varies widely both in structure and in genomic content across the phylum. The organelle is characterized by massive gene migrations to the nucleus, sequence rearrangements and drastic functional reductions in some species. Recent third generation sequencing studies have reignited an interest for elucidating the extensive diversity displayed by the mitochondrial genomes of apicomplexans and their intriguing genomic features. The underlying mechanisms of gene transcription and translation are also ill-understood. In this review, we present the state of the art on mitochondrial genome structure, composition and organization in the apicomplexan phylum revisiting topological and biochemical information gathered through classical techniques. We contextualize this in light of the genomic insight gained by second and, more recently, third generation sequencing technologies. We discuss the mitochondrial genomic and mechanistic features found in evolutionarily related alveolates, and discuss the common and distinct origins of the apicomplexan mitochondria peculiarities.

Mitochondrial genomes in Perkinsus decode conserved frameshifts in all genes

“…mtDNAs are relatively simple molecules encoding single copies of genes for the three common myzozoan mitochondrial proteins (COB, COX1, COX3) and fragmented rRNAs, and they lack encoded tRNAs. Thus, while the coding capacity is equivalent to other myzozoans, the high level of mtDNA amplification, fragmentation and recombination seen in dinoflagellates, chromerids and select apicomplexans such as Toxoplasma , suggests that these latter traits are derived and have occurred multiple times independently (Jackson et al 2007; Nash et al 2008; Waller and Jackson 2009; Feagin et al 2012; Jackson et al 2012; Flegontov et al 2015; Berná et al 2021; Mathur et al 2021; Namasivayam et al 2021). Nevertheless, genome rearrangement is seen also in Perkinsus spp.…”

“…All extant mitochondria are derived from an ancient endosymbiosis of an alpha-proteobacterium within the eukaryotic common ancestor, and most have retained some form of the original prokaryotic genome (Roger et al 2017). However, despite their common origin and generally conserved functions, mitochondrial genomes (mtDNAs) display a remarkable diversity of states (Gray et al 2001; Burger et al 2003; Smith and Keeling 2015; Gagat et al 2017; Roger et al 2017; Berná et al 2021).…”

“…In some instances mitochondria are so derived, reduced and specialized (e.g. hydrogenosomes and mitosomes) that they lack the electron transport chain components and have lost their mtDNAs completely (Maguire and Richards 2014; Roger et al 2017; Berná et al 2021). The architecture of the remaining organelle genomes are primarily linear, single chromosomes, which often appear circular in sequence assemblies due to various stabilizing inverted end-structures such as terminal inverted repeats (TIRs) that cause false in-silico circularization (Cavalier-Smith 2018; Berná et al 2021).…”

“…The Myzozoa, which comprise dinoflagellates, apicomplexans, chrompodellids and perkinsids (Flegontov et al 2015; Roger et al 2017; Cavalier-Smith 2018), represent some of the most reduced and divergent mtDNAs known to date (Flegontov et al 2015; Roger et al 2017). They encode the smallest number of proteins for any organelle genome — COB, COX1, COX3 — with the gene for COB apparently completely lost in the chrompodellid Chromera velia (Waller and Jackson 2009; Flegontov et al 2015; Roger et al 2017; Berná et al 2021). Moreover, rRNAs in myzozoan mtDNAs are highly fragmented with no evidence of reassembly at the RNA level by splicing, and they entirely lack 5S rRNA (Waller and Jackson 2009; Feagin et al 2012; Berná et al 2021).…”

“…They encode the smallest number of proteins for any organelle genome — COB, COX1, COX3 — with the gene for COB apparently completely lost in the chrompodellid Chromera velia (Waller and Jackson 2009; Flegontov et al 2015; Roger et al 2017; Berná et al 2021). Moreover, rRNAs in myzozoan mtDNAs are highly fragmented with no evidence of reassembly at the RNA level by splicing, and they entirely lack 5S rRNA (Waller and Jackson 2009; Feagin et al 2012; Berná et al 2021). The architecture of myzozoan mtDNAs is multiform and complex.…”