Comparative Analysis of CpG Sites and Islands Distributed in Mitochondrial DNA of Model Organisms

Abstract

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.

Characterisation of the Complete Mitochondrial Genome of Critically Endangered Mustela lutreola (Carnivora: Mustelidae) and Its Phylogenetic and Conservation Implications

“…A similar overall pattern of CpG islands distribution has been described in the Canis lupus familiaris mitogenome, where the CpG-rich region of 271 bp is located in the D-loop (between 16,179 and 16,449 bp) and covers the VNTR region. In the mitochondrial genomes of primates ( Pan troglodytes ellioti and Homo sapiens sapiens ), as well as Danio rerio , Latimeria chalumnae , Crocodylus porosus and Gallus gallus, CpG islands were identified most often in coding sequences (e.g., rrnS , nad 5 , cyt b ) [ 129 ]. CpG islands in the control region have been also described in humans [ 130 , 131 ].…”

DNA methylation differs extensively between strains of the same geographical origin and changes with age in Daphnia magna

“…Our data had a mitochondrial CpG average methylation rate of 0.8% for the ‘3x u CH’ and 0.65% for the ‘No-CH’ datasets, which when subtracted from the global CpG percentages (‘3x u CH’ dataset: 1.3–0.8% = 0.5%) were in the range of other estimates derived from D. magna . This lack of mitochondrial DNA methylation has not been confirmed in D. magna or any invertebrates beyond C. gigas [ 13 ], so the mitochondria method should be interpreted with caution (see [ 66 ] for mitochondrial CpG distributions in animals). We argue that by performing a well-replicated experiment in which there are 24 versus 23 replicates for each level of factor tested (Age/Strain/Food), the effect of false-positive CpGs resulting from non-conversion of cytosines was minimised.…”

Molecular differences in mitochondrial DNA genomes of dogs with malignant mammary tumours

“…The in silico analyses revealed that there might be a 313 bp-long CpG island at the positions 16 137…16 449 (%GC = 0.40) in the canine mitochondrial VNTR region, which in some circumstances might be methylated or demethylated. 62 A high level of mitochondrial oxidative stress can lead to mtDNA demethylation [63][64][65] ; therefore, it cannot be excluded that changes in the VNTR region observed in mammary gland tumours might induce epigenetic modifications in the mitochondrial CpG island. The molecular landscape (383 SNP, 32 indels/length polymorphisms, 4 mutations, 137 heteroplasmic positions and 1 indel mutation) of the changes in the mtDNA presents a wide range of alterations identified in almost every protein-coding gene, in two rRNA-coding genes, in 8 of 22 tRNA genes, and in the non-coding region.…”