Mitochondrial DNA in Hydrozoan Cnidarians

It is now widely accepted that the mitochondrion, the powerhouse of the cell, originated from the endosymbiosis of an alpha-proteobacterium. Subsequent transfer of genetic material from the proto-mitochondrion to the host cell nucleus has reduced the number of genes that make up the genome of the mitochondrion (mtDNA) in many organisms, including animals. Some studies have suggested that the highly reduced size of the mtDNA genome is associated with the evolution of multicellularity in animals (Metazoa)^{e.g. 1}. Yet, the evolution of the mtDNA in animals is far from straightforward, particularly in non-bilaterians², reflecting a more general pattern in the broader Eukaryota³.

Cnidaria (jellyfish, hydroids, corals, anemones and the likes) is a perfect illustrative case where the mtDNA has lost nearly all transfer RNA (tRNA) genes. In addition, the mtDNA can be linear and in several pieces with extra protein genes⁴. The linearization of the mtDNA in Cnidaria occurred sometime after the emergence of Medusozoa, a clade including all cnidarian groups with a medusoid stage^5. Twice within Medusozoa, the linear mitochondrial genome has been broken into multiple chromosomes, in Cubozoa (box jellyfish) and the genus Hydra (hydras). Hydrozoa is the most speciose meduzosoan clade by far, a diversity also reflected in the organization of the mtDNA (five mitogenome organizations described to date)^5-7.

Figure 1: Transcription of the mtDNA in humans. Arrows show the different polycistronic transcripts originating at several sites (HSP and LSP) within the D-loop region. From Selwood et al. (2000) Biochemical Society Transactions.

The mechanisms involved in the expression of linear chromosomes are different from those of circular molecules. In mammals, for example, a structure in the shape of a “D” (the D-loop) is responsible for the replication of the circular mtDNA and also the site where the two origins of transcriptions (for the light and heavy strands) are located (Figure 1)⁸. First, precursor polycistronic transcripts (containing multiple genes) are synthetized, before single-gene (monocistronic) mature messenger RNAs (mRNAs) are created by the excision of tRNAs (the tRNA punctuation model)⁹ and polyadenylation (addition of adenosine (A) at the 3’end of the mRNAs). Then, mRNAs are translated into proteins.

In Hydrozoa, the loss of most of the mt-tRNAs and the linear nature of the mtDNA would suggest an alternative mechanism for the synthesis of mitochondrial mRNAs (mt-mRNAs). In a recent study, we compared the transcriptome (obtained from RNA sequencing data) from several hydrozoan species⁷. In one group (Hydroidolina species excluding the order Aplanulata), the mtDNA is transcribed in two directions starting from a single large intergenic region: one monocistronic transcript containing the large ribosomal RNA subunit (rnl) and one polycistronic transcript containing the remaining of the mitochondrial genes. Stem-loop structures presented at key positions are recognition sites for cleavage of the pre-mRNA into mature mRNAs containing one to five genes (Figure 2). This new model sheds lights into the gene expression in linear mtDNAs.

Figure 2: Mitochondrial gene expression in non-aplanulatan Hydroidolina. (A) mtDNA organization in the siphonophore Physalia physalis assembled from a large EST dataset. Grey lines correspond to the contigs assembled. Missing features (tRNAs, IGRs, CR) are shown with dotted lines. (B) Predicted model of mt-mRNA expression based on findings from P. physalis. Color-codes are the same as in (A). Grey horizontal arrows are the two pre-mRNA transcripts, the larger being polycistronic. Dark vertical arrows correspond to regions of pre-mRNA excision from the “tRNA punctuation model”; red and blue arrows are the additional excision sites predicted from our model for hydrozoan mt-mRNA expression. We predict that stage 1 and 2 are simultaneous.

 Cubozoa is another medusozoan cnidarian clade where the linear mtDNA underwent a high level of segmentalization, with eight mitochromosomes reported to be harboring between one and four genes and flanked by large inverted repeats (IRs)^5,10. Future studies exploring the mitochondrial gene expression in this group might provide additional fascinating mechanisms for the evolution and expression of genes in linear (mito)chromosomes.

By Ehsan Kayal

References:

1. Lavrov DV. 2007. Key transitions in animal evolution: a mitochondrial DNA perspective. Integrative and Comparative Biology 47(5): 734-743.
2. Lavrov DV. 2014. Mitochondrial genomes in invertebrate animals. In Molecular life sciences. Springer, New York, pp 1–8.
3. Smith DR, & Keeling PJ. 2015. Mitochondrial and plastid genome architecture: Reoccurring themes, but significant differences at the extremes. Proceedings of the National Academy of Sciences, 201422049.
4. Osigus HJ, Eitel M, Bernt M, Donath A, Schierwater B. 2013. Mitogenomics at the base of Metazoa. Molecular Phylogenetics and Evolution, 69(2): 339-351.
5. Kayal E, Bentlage B, Collins AG, Kayal M, Pirro S, Lavrov, DV. 2012. Evolution of linear mitochondrial genomes in medusozoan cnidarians. Genome Biology and Evolution 4(1): 1-12.
6. Voigt O, Erpenbeck D, Wörheide, G. 2008. A fragmented metazoan organellar genome: the two mitochondrial chromosomes of Hydra magnipapillata. BMC Genomics 9(1): 350.
7. Kayal E, Bentlage B, Cartwright P, Yanagihara AA, Lindsay DJ, Hopcroft RR, Collins AG. 2015. Phylogenetic analysis of higher-level relationships within Hydroidolina (Cnidaria: Hydrozoa) using mitochondrial genome data and insight into their mitochondrial transcription. PeerJ 3: e1403.
8. Bernt M, Braband A, Schierwater B, Stadler PF. 2013. Genetic aspects of mitochondrial genome evolution. Molecular Phylogenetics and Evolution 69(2): 328-338.
9. Ojala D, Merkel C, Gelfand R, Attardi G. 1980. The tRNA genes punctuate the reading of genetic information in human mitochondrial DNA. Cell 22: 393–403.
10. Smith DR, Kayal E, Yanagihara AA, Collins AG, Pirro S, Keeling PJ. 2012. First complete mitochondrial genome sequence from a box jellyfish reveals a highly fragmented linear architecture and insights into telomere evolution. Genome Biology and Evolution 4(1): 52-58.