Abstract
Background: The mitochondrial protein import complexes arose early in eukaryogenesis. Most of the components of the protein import pathways predate the last eukaryotic common ancestor. For example, the carrier-insertase TIM22 complex comprises the widely conserved Tim22 channel core. However, the auxiliary components of fungal and animal TIM22 complexes are exceptions to this ancient conservation. Methods: Using comparative genomics and phylogenetic approaches, we identified precisely when each TIM22 accretion occurred. Results: In animals, we demonstrate that Tim29 and Tim10b arose early in the holozoan lineage. Tim29 predates the metazoan lineage being present in the animal sister lineages, choanoflagellate and filastereans, whereas the erroneously named Tim10b arose from a duplication of Tim9 at the base of metazoans. In fungi, we show that Tim54 has representatives present in every holomycotan lineage including microsporidians and fonticulids, whereas Tim18 and Tim12 appeared much later in fungal evolution. Specifically, Tim18 and Tim12 arose from duplications of Sdh3 and Tim10, respectively, early in the Saccharomycotina. Surprisingly, we show that Tim54 is distantly related to AGK suggesting that AGK and Tim54 are extremely divergent orthologues and the origin of AGK/Tim54 interaction with Tim22 predates the divergence of animals and fungi. Conclusions: We argue that the evolutionary history of the TIM22 complex is best understood as the neutral structural divergence of an otherwise strongly functionally conserved protein complex. This view suggests that many of the differences in structure/subunit composition of multi-protein complexes are non-adaptive. Instead, most of the phylogenetic variation of functionally conserved molecular machines, which have been under stable selective pressures for vast phylogenetic spans, such as the TIM22 complex, is most likely the outcome of the interplay of random genetic drift and mutation pressure.
Highlights
Mitochondria evolved from an ancient alphaproteobacterial endosymbiont (Martijn et al, 2018; Roger et al, 2017)
The Sengers syndrome-associated AGK was originally shown to catalyze the phosphorylation of acylglycerols to lysophosphatidic and phosphatidic acid in the mitochondrial inner membrane (MIM) (Bektas et al, 2005), but has recently been identified as a TIM22 complex member in human cells (Kang et al, 2017; Vukotic et al, 2017)
We could not identify Tim29 in Gallus gallus; orthologous sequences were recovered from other birds and reptiles, suggesting loss of Tim29 is limited to chickens
Summary
Mitochondria evolved from an ancient alphaproteobacterial endosymbiont (Martijn et al, 2018; Roger et al, 2017). The integration of the symbiont into host cell processes required the evolution of dedicated machinery for the import of host-encoded proteins (Roger et al, 2017). Proteins imported into the mitochondria require several dedicated protein complexes to ensure proper sorting and assembly into mitochondrial subcompartments, including the mitochondrial outer membrane (MOM), the mitochondrial inner membrane (MIM), the intermembrane space (IMS) and the matrix (Wiedemann & Pfanner, 2017). Conclusions: We argue that the evolutionary history of the TIM22 complex is best understood as the neutral structural divergence of an otherwise strongly functionally conserved protein complex. This view suggests that many of the differences in structure/subunit composition of multi-protein complexes are non-adaptive. Most of the phylogenetic variation of functionally conserved molecular machines, which have been under stable selective pressures for vast phylogenetic spans, such as the TIM22 complex, is most likely the outcome of the interplay of random genetic drift and Invited Reviewers version 1
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