Introduction

Mitochondrial (mt) plasmids are defined as small (< 1-15 kb), autonomously replicating genetic elements that show no significant homology to mitochondrial DNA and have independent evolutionary origins. They are structurally diverse and are widely distributed in certain taxa (e.g., filamentous fungi), yet absent in others (e.g., animals; see Chap. 9, in this volume). They differ from bacterial plasmids in several important areas: most mt plasmids encode their own polymerase(s) that control key steps in replication, thus they are more like viruses or bacteriophages and, except in rare incidences, mt plasmids do not provide an obvious selective advantage to their host (see Chap. 8, in this volume). While most are considered to be benign, a few mt plasmids appear to provide a small benefit to their host (Leon et al. 1989; Bok et al. 2000), while others are clearly detrimental and are associated with senescence (reviewed in Griffiths 1992) or attenuation of virulence (reviewed in Bertrand and Baid-yaroy 2002). Structural and phenotypic differences between mt plasmids and their presumed bacterial counterparts, including bacteriophages, likely reflect unique selective pressures experienced in residing in an organelle that has been transformed since its presumed former existence as a free-living a-proteobacterial-like bacterium (Andersson 1998). In general terms, mt plas-mids can be considered to be selfish genetic elements that co-evolved with mitochondria and have adapted to residing within an organelle that has been extensively renovated. As expected of selfish genetic elements, mitochondrial plasmids exhibit drive and directly or indirectly increase their transmission frequencies by manipulating the inheritance of their mitochondrial host and can spread via lateral transfer mechanisms (reviewed in Griffiths 1995; Ken-nell, submitted for publication). In short, they may have had a significant impact on the development of eukaryotic cells and, in some lineages, continue to exert great influence over their hosts. Thus, they are of interest due to their unique evolutionary history and ways in which they influence mitochondrial function and evolution.

Mitochondrial plasmids can be categorized into discrete groups based on the type of nucleic acid associated with the replicative form: DNA, RNA, or those that have both RNA and DNA replication intermediates. DNA plasmids encode a DNA-dependent DNA polymerase and are subdivided into circular and linear types (see Chap. 8, in this volume). Mitochondrial double-stranded RNA elements that encode an RNA-dependent RNA polymerase are formally recognized as "mitoviruses" within the Narnaviridae family of naked viruses (Wickner et al. 2000); however, these elements lack an extracellular form and do not form virus particles, thus they have greater similarity to plas-mids than to viruses (Kennell, submitted for publication). Retroplasmids are distinguished from DNA and RNA plasmids in that they encode an RNA-dependent DNA polymerase (i.e., reverse transcriptase, or RT) and replicate through an RNA intermediate. Retroplasmids are divided into two groups based on structure, circular and linear, and each group has distinct replication mechanisms. Satellite plasmids represent an additional group of mt plasmids and are defined as genetic elements that depend on another plas-mid for replication, yet are not derived from the helper element. The basic structural features of retroplasmids reported to date are illustrated in Fig. 1.

The origin of retroplasmids is thought to precede the endosymbiotic event that introduced the a-proteobacterial-like organism into the nascent eukary-otic cell. Phylogenetic analysis of retroplasmid RTs indicates that they form a monophyletic clade (Fig. 2) and are deeply rooted in RT phylogeny (Xiong and Eickbush 1990). This has led to the suggestion that retroplasmids are "molecular fossils", which are defined as contemporary genetic elements that are ancient in origin and provide insight into the evolutionary past (Maizels and Wiener 1993). If so, they are possible progenitors to a wide range of retroelements, including mobile group II introns, non-LTR retrotransposons, and perhaps telomerase (Wang and Lambowitz 1993; Eickbush 1997; Walther and Kennell 1999).

While the focus of this volume of Microbial Monographs is on linear genetic elements, the discovery of linear retroplasmids is relatively recent and many details of their replication cycle have yet to be characterized. In contrast, the Mauriceville retroplasmid was the first reported circular mitochon-drial extrachromosomal element (Collins et al. 1981) and is currently the

pRS224-1

Fig. 1 Structural features of mitochondrial retroplasmids. The 3.6 kb Mauriceville plasmid of Neurospora crassa, 3.7 kb Varkud, Maddur-1, and Maddur-2 plasmids of N. intermedia, and 2.6 kb pThr1 plasmid of Trichoderma harzianum are circular dsDNAs that contain a single large open reading frame that encodes a reverse transcriptase (gray box). The VS plasmid of N. intermedia is an 881 bp circular dsDNA that lacks large ORFs and replicates as a satellite of the Varkud retroplasmid. The 1.9 kb pFOXC2 and pFOXC3 plasmids of Fusarium oxysporum are linear dsDNAs that have a clothespin structure with a hairpin at one end and three to five copies of a 5 bp repeat at the other terminus (small vertical bars). The 5.0 kb pRS224-1 plasmid of Rhizoctonia solani is a covalently-closed linear dsDNA having hairpins at both termini. Both clothespin and double-hairpin linear retroplasmids contain a single large ORF that encodes a reverse transcriptase (gray box)

pRS224-1

Fig. 1 Structural features of mitochondrial retroplasmids. The 3.6 kb Mauriceville plasmid of Neurospora crassa, 3.7 kb Varkud, Maddur-1, and Maddur-2 plasmids of N. intermedia, and 2.6 kb pThr1 plasmid of Trichoderma harzianum are circular dsDNAs that contain a single large open reading frame that encodes a reverse transcriptase (gray box). The VS plasmid of N. intermedia is an 881 bp circular dsDNA that lacks large ORFs and replicates as a satellite of the Varkud retroplasmid. The 1.9 kb pFOXC2 and pFOXC3 plasmids of Fusarium oxysporum are linear dsDNAs that have a clothespin structure with a hairpin at one end and three to five copies of a 5 bp repeat at the other terminus (small vertical bars). The 5.0 kb pRS224-1 plasmid of Rhizoctonia solani is a covalently-closed linear dsDNA having hairpins at both termini. Both clothespin and double-hairpin linear retroplasmids contain a single large ORF that encodes a reverse transcriptase (gray box)

Fig. 2 Phylogenetic analysis of representative reverse transcriptase protein sequences. Amino acid sequences encompassing highly conserved domains I through VII (as described by Xiong and Eickbush 1990) were aligned in ClustalX and a maximum parsimony search using PAUP 4.0b10 generated 15 trees. The tree shown represents a strict consensus of recovered topologies and was rooted using the prokaryotic ms-DNAs. Numbers indicate the bootstrap support for the recovered clades. The accession numbers (in parentheses) of the elements used are as follows: EC86 (P23070), Mx162 (P23072), Mx65 (P23071), pRS224 (BAA94080), Bc GRII (ZP_00236429), Sa GRII (ZP_00784712), Sc GRII (AAA67532), Nc GRII (S07649), Vi GRII (AAB95256), Mp GRII (NP_054460), Copia (P04146), Ty1 (NP_058152), DIRS (AAA33195), hTERT (NP_937983), mTERT (NP_033380), Sp TERT (AAC49803), Ca TERT (AAF26733), RTL (CAA38646), pEt2.0L (CAA40486), pThr1 (NP_862333), pFOXC1 (AAD12231), pFOXC2 (NP_862680), pFOXC3 (NP_862679), pVarkud (AAA70286), pMauriceville (NP_041729), pMaddur1 (AAU25926), DHB (AAK85436), HHB (AAB59972), WHB (NP_671813), MMLV (P03355), HIV (AAL12183), RSV (CAA48535), CaMV (NP_056728), Gypsy (P10401), TY3 (AAA98435), Bm R2 (T18197), CRE1 (AAA75435), RTE1 (AAB71003), I Factor (AAA70222), Human L1 (AAC51279), Lian Aa1 (AAB65093), Nc Tad1 (AAA21781), Gg CR1 (AAA49027), Bm R1 (BAD82946), Dm Jockey (P21328), TART (T13173)

most thoroughly studied mitochondrial plasmid. Consequently, a brief review of its replication cycle is appropriate as features show direct similarity to certain steps in the replication of linear retroplasmids and can serve as a valuable model for retroplasmid replication in general.

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