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Several studies have linked mitochondrial genetic variation to phenotypic modifications; albeit the identity of the mitochondrial polymorphisms involved remains elusive. The search for these polymorphisms led to the discovery of small noncoding RNAs, which appear to be transcribed by the mitochondrial DNA ("small mitochondrial RNAs"). This contention is, however, controversial because the nuclear genome of most animals harbors mitochondrial pseudogenes (NUMTs) of identical sequence to regions of mtDNA, which could alternatively represent the source of these RNAs. To discern the likely contributions of the mitochondrial and nuclear genome to transcribing these small mitochondrial RNAs, we leverage data from six vertebrate species exhibiting markedly different levels of NUMT sequence. We explore whether abundances of small mitochondrial RNAs are associated with levels of NUMT sequence across species, or differences in tissue-specific mtDNA content within species. Evidence for the former would support the hypothesis these RNAs are primarily transcribed by NUMT sequence, whereas evidence for the latter would provide strong evidence for the counter hypothesis that these RNAs are transcribed directly by the mtDNA. No association exists between the abundance of small mitochondrial RNAs and NUMT levels across species. Moreover, a sizable proportion of transcripts map exclusively to the mtDNA sequence, even in species with highest NUMT levels. Conversely, tissue-specific abundances of small mitochondrial RNAs are strongly associated with the mtDNA content. These results support the hypothesis that small mitochondrial RNAs are primarily transcribed by the mitochondrial genome and that this capacity is conserved across Amniota and, most likely, across most metazoan lineages.

genome biology and evolution

The Genomic Origins of Small Mitochondrial RNAs: Are They Transcribed by the Mitochondrial DNA or by Mitochondrial Pseudogenes within the Nucleus (NUMTs)?