Abstract
The vertebrate mitochondrial genome is characterized by an exceptional organization evolving towards a reduced size. However, the persistence of a non-coding and highly variable control region is against this evolutionary trend that is explained by the presence of conserved sequence motifs or binding sites for nuclear-organized proteins that regulate mtDNA maintenance and expression. We performed a comparative mitogenomic investigation of the non-coding control region to understand its evolutionary patterns in Clupeoid fishes which are widely distributed across oceans of the world, exhibiting exemplary evolutionary potential. We confirmed the ability of sequence flanking the conserved sequence motifs in the control region to form stable secondary structures. The existence of evolutionarily conserved secondary structures without primary structure conservation suggested the action of selective constraints towards maintaining the secondary structure. The functional secondary structure is maintained by retaining the frequency of discontinuous AT and TG repeats along with compensatory base substitutions in the stem forming regions which can be considered as a selective constraint. The nucleotide polymorphism along the flanking regions of conserved sequence motifs can be explained as errors during the enzymatic replication of secondary structure-forming repeat elements. The evidence for selective constraints on secondary structures emphasizes the role of the control region in mitogenome function. Maintenance of high frequency of discontinuous repeats can be proposed as a model of adaptive evolution against the mutations that break the secondary structure involved in the efficient regulation of mtDNA functions substantiating the efficient functioning of the control region even in a high nucleotide polymorphism environment.
Data availability
All DNA sequences used in this study are from the publicly available NCBI, GenBank database, accession numbers are included in the manuscript Online Resource 1.
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Acknowledgements
The authors would like to thank Director, ICAR-Central Marine Fisheries Research Institute (CMFRI), and Dr. P. Vijayagopal (Head, Marine Biotechnology Division, ICAR-CMFRI) for providing facilities to carry out this work. WS received a Senior Research Fellowship from the ICAR-NICRA project.
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This work was carried out under the institute project MBT/GEN/25 receiving funding support from the Indian Council of Agricultural Research (ICAR).
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WS conceived the idea, executed the research, and drafted the manuscript. SS coordinated the research and revised the manuscript. AG reviewed the manuscript and approved it. All authors gave final approval for publication and agreed to be held accountable for the work performed therein.
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This article does not contain any studies with human participants performed by any of the authors. All DNA sequences used in this study are from the publicly available database, GenBank, and accession numbers are included in the manuscript Online Resource 1.
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Sebastian, W., Sukumaran, S. & Gopalakrishnan, A. The signals of selective constraints on the mitochondrial non-coding control region: insights from comparative mitogenomics of Clupeoid fishes. Genetica 149, 191–201 (2021). https://doi.org/10.1007/s10709-021-00121-x
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DOI: https://doi.org/10.1007/s10709-021-00121-x