The inversion of the Control Region in three mitogenomes provides further evidence for an asymmetric model of vertebrate mtDNA replication.

Miguel M Fonseca,D James Harris,David Posada,Dan Mishmar

doi:10.1371/journal.pone.0106654

Miguel M Fonseca, D James Harris + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0106654

Copy DOI

Journal: PloS one	Publication Date: Sep 30, 2014
Citations: 99	License type: CC BY 4.0

Affiliation: Universidade de Vigo, University of Porto

Abstract

Mitochondrial genomes are known to have a strong strand-specific compositional bias that is more pronounced at fourfold redundant sites of mtDNA protein-coding genes. This observation suggests that strand asymmetries, to a large extent, are caused by mutational asymmetric mechanisms. In vertebrate mitogenomes, replication and not transcription seems to play a major role in shaping compositional bias. Hence, one can better understand how mtDNA is replicated – a debated issue – through a detailed picture of mitochondrial genome evolution. Here, we analyzed the compositional bias (AT and GC skews) in protein-coding genes of almost 2,500 complete vertebrate mitogenomes. We were able to identify three fish mitogenomes with inverted AT/GC skew coupled with an inversion of the Control Region. These findings suggest that the vertebrate mitochondrial replication mechanism is asymmetric and may invert its polarity, with the leading-strand becoming the lagging-strand and vice-versa, without compromising mtDNA maintenance and expression. The inversion of the strand-specific compositional bias through the inversion of the Control Region is in agreement with the strand-displacement model but it is also compatible with the RITOLS model of mtDNA replication.

Highlights

Mitochondrial DNA has been widely used as a molecular marker because of its maternal transmission, haploidy, limited recombination, high mutation rate and availability in animal cells
They have variable copy number of non-coding regions (NCR): 3 (J. grypotus), 4 (T. ocellatum), and 5 (J. belangerii). Of these NCR we identified 2 CR in the mitogenomes of T. ocellatum and of J. grypotus and 1 CR in the mitogenome of J. belangerii
In T. ocellatum mitogenome transfer RNAs (tRNAs)-Glu inverted its transcription polarity (coding strand inversion determined by ARWEN and MiTFi (E-value = 3.30e-10), Figure 3), which is contrary of its original GenBank annotation

Summary

Introduction

Mitochondrial DNA has been widely used as a molecular marker because of its maternal transmission, haploidy, limited recombination, high mutation rate and availability in animal cells. The discovery that mutations in mtDNA can cause human diseases has increased the interest of the scientific community in understanding mtDNA evolution or its maintenance [1] The latter consists of the processes that keep mtDNA viable, which in turn will have consequences at the cell biological and organismal level and is, in part, dependent of molecular processes such as mtDNA replication and transcription. The vertebrate mitogenome is typically a circular, doublestranded DNA molecule of ,17 kb that encodes 13 proteins essential for the function of the respiratory chain as they constitute key components of the electron transport chain complexes required for oxidative phosphorylation. Mitochondrial genomes are known to have a strong strand-specific compositional bias [2] with the individual mtDNA strands being distinguished by its uneven guanine content: the heavy-strand (Hstrand) is guanine rich whereas the light-strand (L- strand) is guanine poor [3]

Methods

Results

Conclusion