Trends in Genetics
Volume 22, Issue 2, February 2006, Pages 90-95
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Bacteriophage origins of mitochondrial replication and transcription proteins

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Mounting evidence suggests that key components of the mitochondrial transcription and replication apparatus are derived from the T-odd lineage of bacteriophage rather than from an α-Proteobacterium, as the endosymbiont hypothesis would predict. We propose that several mitochondrial replication genes were acquired together from an ancestor of T-odd phage early in the evolution of the eukaryotic cell, at the time of the mitochondrial endosymbiosis. We further propose that at a later stage the single-subunit RNA polymerase, originally acquired for mitochondrial DNA replication, was co-opted to serve in mitochondrial transcription.

Introduction

Mitochondria are the organelles responsible for most of the energy production of the cell, in addition to serving other important roles in processes such as iron homeostasis, intermediary metabolism and apoptosis. Although several recent theories have presented differing viewpoints on the origin of mitochondria and the eukaryotic cell (reviewed in Ref. [1]), one constant in these scenarios is that the ancestor of the mitochondrion was once a free-living (eu)bacterium, almost certainly an α-Proteobacterium [2]. The size and structure of the mitochondrial genome varies greatly in different eukaryotes; it is highly reduced in gene content compared with its bacterial ancestor. For example, there are 97 genes in the most gene-rich mitochondrial genome (the heterotrophic flagellate Reclinomonas americana [3]) compared with 835 genes in the smallest α-proteobacterial genome sequenced so far (Rickettsia prowazekii [4]).

Because mitochondria retain a genome, they require enzyme systems for mitochondrial DNA (mtDNA) replication and expression. To date, details of how mtDNA is replicated and transcribed have been partially elucidated in only a few model eukaryotic systems 5, 6, 7, 8. Given the bacterial ancestry of mitochondria, one might expect that essential elements of the transcription and replication apparatus of the organelle would resemble those of eubacteria. However, this is not the case for three of the main components of this machinery – the RNA polymerase (RNAP), the replicative primase-helicase and the DNA polymerase (DNAP), which appear instead to have a shared ancestry with proteins encoded by T-odd bacteriophages (see Glossary).

Section snippets

RNA polymerase

Although we would expect that a eubacterial-type, multi-subunit RNAP would be responsible for transcription in mitochondria, these organelles use a mitochondrial single-subunit RNAP (mt-ssRNAP), as first demonstrated in yeast [9] and later in humans [10] and plants [11]. Homologs of the mt-ssRNAP have been identified throughout the eukaryotic domain [12], suggesting that this gene was acquired once, early in eukaryotic evolution. However, the source and timing of this acquisition remain

DNA replication in T7 phage and mitochondria

The system replicating the T7 phage genome is one of the simplest and most well characterized, relying on only seven essential proteins [27]. Of particular interest here are the phage-encoded RNAP (gp1), primase-helicase (gp4), DNAP (gp5), single-strand DNA-binding protein (gp2.5) and a host-encoded thioredoxin that functions as a processivity factor [31]. The DNA replication pathway of T7 phage exhibits several parallels with what we currently know about mtDNA replication.

Corroborating evidence

The T-odd phage and mitochondria share other key characteristics linked to DNA replication. These include the prevalence of linear mitochondrial genomes and concatemerization (Box 1). Furthermore, linear mitochondrial plasmids might be relics of a T-odd phage [44] that permitted the emergence of linear mitochondrial genomes by providing a means of end replication [45].

It is also striking that the RNAP, DNAP and primase-helicase genes are all found close to each other at the 5′ end in the

Concluding remarks

Parallels between plant mitochondrial and phage T4 genome replication, on the one hand, and chloroplast and phage T7 genome replication, on the other, have been noted previously 46, 47. In this article, we have outlined the similarities evident in the replication strategies of the T-odd phage group and various additional mitochondrial systems, consistent with the thesis that replication proteins were initially acquired from a T-odd phage progenitor and seconded to function in mtDNA replication.

Acknowledgements

We thank members of the Gray laboratory for insight and critical reading of this article. This research was supported by a grant awarded to M.W.G. from the Canadian Institutes of Health Research (MOP-4355). M.W.G. acknowledges salary support from the Canada Research Chairs Program and the Canadian Institute for Advanced Research.

Glossary

Endosymbiont:
denotes the proto-mitochondrial eubacterium, most probably sharing ancestry with α-Proteobacteria that evolved into the mitochondrion.
T-odd bacteriophage:
refer to T3 and T7 bacteriophages and their close relatives, members of a group of lytic bacteriophages known to infect γ-proteobacteria. The T-odd phages are characterized by an icosahedral protein head and a double-stranded DNA genome of ∼40 kb that encodes an ssRNAP.
ssRNAP:
is the abbreviation for a small group of single-subunit

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