Abstract
Simple SummaryIn recent years, the existence of methylation of mammalian mitochondrial DNA (mtDNA) has been discussed. The current state of knowledge indicates that mtDNA is poorly methylated; in fact, it only accounts for 2–8% methylated sites and its pattern is unknown. The lack of comprehensive information on the mtDNA methylation pattern prompted us to investigate the distribution of guanine-cytosine-rich sequences (CpG) in different animal species. The aim of the study was to determine the localization of CpG sites and islands in mtDNA of model organisms. The CpG sites and islands found in vertebrates and invertebrates indicate a diversified pattern of CpG distribution. Generally, the number of observed CpG sites of the mitochondrial genome was higher in the analysed vertebrates than in the invertebrates. However, there was no relationship between the frequency of the CpG sites in the mitochondrial genome and the complexity of the analysed organism. The distribution of the CpG sites for transfer RNA (tRNA) coding genes was usually cumulated in a larger CpG region in the vertebrates.The information about mtDNA methylation is still limited, thus epigenetic modification remains unclear. The lack of comprehensive information on the comparative epigenomics of mtDNA prompts comprehensive investigations of the epigenomic modification of mtDNA in different species. This is the first study in which the theoretical CpG localization in the mtDNA reference sequences from various species (12) was compared. The aim of the study was to determine the localization of CpG sites and islands in mtDNA of model organisms and to compare their distribution. The results are suitable for further investigations of mtDNA methylation. The analysis involved both strands of mtDNA sequences of animal model organisms representing different taxonomic groups of invertebrates and vertebrates. For each sequence, such parameters as the number, length, and localization of CpG islands were determined with the use of EMBOSS (European Molecular Biology Open Software Suite) software. The number of CpG sites for each sequence was indicated using the newcpgseek algorithm. The results showed that methylation of mtDNA in the analysed species involved mitochondrial gene expression. Our analyses showed that the CpG sites were commonly present in genomic regions including the D-loop, CYTB, ND6, ND5, ND4, ND3, ND2, ND1, COX3, COX2, COX1, ATP6, 16s rRNA, and 12s rRNA. The CpG distribution in animals from different species was diversified. Generally, the number of observed CpG sites of the mitochondrial genome was higher in the vertebrates than in the invertebrates. However, there was no relationship between the frequency of the CpG sites in the mitochondrial genome and the complexity of the analysed organisms. Interestingly, the distribution of the CpG sites for tRNA coding genes was usually cumulated in a larger CpG region in vertebrates. This paper may be a starting point for further research, since the collected information indicates possible methylation regions localized in mtDNA among different species including invertebrates and vertebrates.
Highlights
Most animal mitochondrial genomes are about 16.5 kbp in length, whereas plant mitochondrial genomes range between 200 and 2000 kbp [1]
Transcription begins from promoters: LSP and HSP2 encode 13 protein-coding genes involved in the oxidative phosphorylation (OXPHOS) and 22 transfer RNAs (tRNAs), whereas
The positions of the CpG islands in the mitochondrial DNA (mtDNA) of 12 organisms are presented in Tables 2 and 3
Summary
Most animal mitochondrial genomes are about 16.5 kbp (kilo base pairs) in length, whereas plant mitochondrial genomes range between 200 and 2000 kbp [1]. The mammalian mitochondrial genome is a circular double-stranded DNA (dsDNA) molecule containing 13 proteincoding genes, 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs) genes, and one non-coding control region (D-loop region) [2]. The exception is the mtDNA genome of Caenorhabditis elegans, which lacks the ATP8 gene [3] and the non-coding AT region. The non-coding region of mtDNA contains an origin of replication and three promoters: one for the light strand (LSP) and two for the heavy strand (HSP1 and HSP2). Transcription begins from promoters: LSP and HSP2 encode 13 protein-coding genes involved in the oxidative phosphorylation (OXPHOS) and 22 tRNAs, whereas. HSP1 generates a short transcript containing rRNA genes [4]. MtDNA is packed into structures called nucleoids or mitochromosomes. The major part of the nucleoid constitutes transcription factor A (TFAM), which contributes to mtDNA packing. Any alterations in the TFAM content influence the mitochromosome and, mtDNA is exposed to DNA methyltransferases (DNMTs) [5]
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