The metazoan landscape of mitochondrial DNA gene order and content is shaped by selection and affects mitochondrial transcription

Abstract

Mitochondrial DNA (mtDNA) harbors essential genes in most metazoans, yet the regulatory impact of the multiple evolutionary mtDNA rearrangements has been overlooked. Here, by analyzing mtDNAs from ~8000 metazoans we found high gene content conservation (especially of protein and rRNA genes), and codon preferences for mtDNA-encoded tRNAs across most metazoans. In contrast, mtDNA gene order (MGO) was selectively constrained within but not between phyla, yet certain gene stretches (ATP8-ATP6, ND4-ND4L) were highly conserved across metazoans. Since certain metazoans with different MGOs diverge in mtDNA transcription, we hypothesized that evolutionary mtDNA rearrangements affected mtDNA transcriptional patterns. As a first step to test this hypothesis, we analyzed available RNA-seq data from 53 metazoans. Since polycistron mtDNA transcripts constitute a small fraction of the steady-state RNA, we enriched for polycistronic boundaries by calculating RNA-seq read densities across junctions between gene couples encoded either by the same strand (SSJ) or by different strands (DSJ). We found that organisms whose mtDNA is organized in alternating reverse-strand/forward-strand gene blocks (mostly arthropods), displayed significantly reduced DSJ read counts, in contrast to organisms whose mtDNA genes are preferentially encoded by one strand (all chordates). Our findings suggest that mtDNA rearrangements are selectively constrained and likely impact mtDNA regulation.

Pervasive mitochondrial tRNA gene loss in the clade B of haplosclerid sponges (Porifera, Demospongiae)

“…Thus it is possible that the transfer of atp9 to the nuclear genome simplifies expression of mt-genome. In contrast to atp9 , atp8 is found throughout Metazoa, but has been independently lost in many species, including some molluscs, arrow worms, nematodes, ctenophores, placozoans, and calcareous sponges (Pett and Lavrov, 2015; Shtolz and Mishmar, 2023). Interestingly, atp8 appears to have been lost twice in CBHS: on branches leading to B2 and B5 clades.…”

Connecting species-specific extents of genome reduction in mitochondria and plastids

“…Tremendous diversity also exists in oDNA length and proportion of coding content, genetic structure (gene orderings and repeat regions), and physical structure (linear, branching, circular, and fragmented molecules) of oDNA across eukaryotes (Roger, Muñoz-Gómez, and Kamikawa 2017;Keeling 2010). Explanations for this diversity include the mutational hazard hypothesis (Lynch, Koskella, and Schaack 2006;Smith 2016a), effects of oDNA recombination in some lineages (Edwards et al 2021), and recent work suggesting a functional link between gene order and the control of gene expression in metazoa (Shtolz and Mishmar 2023); the interplay (or independence) of these mechanisms with the environmental influences we propose is an interesting target for future theoretical exploration.…”

The role of mitochondria in sex- and age-specific gene expression in a species without sex chromosomes

“…The most striking sex-specific pattern is that males displayed overall higher expression of mitochondrial genes (except ATP8 ) along with OXPHOS-related MTPs, while females exhibited higher expression of non-OXPHOS MTPs (Figure 2). Importantly, all mitochondrial genes are encoded on the same strand of mtDNA in T. californicus (64), and mtDNA in metazoans is known to be transcribed in polycistrones (65). Overall, the sex-specific transcriptional profiles suggest that metabolic demands may differ between sexes, with males investing more in energy production, while females invest more in mitochondrial maintenance.…”