Precise annotation of tick mitochondrial genomes reveals multiple copy number variation of short tandem repeats and one transposon-like element

• DOI: 10.21203/rs.2.19332/v2
• Publication Date: 2020-02-21T14:14:05Z
• Authors: Ze Chen; Yibo Xuan; Guangcai Liang; Xiaolong Yang; Zhijun Yu; Stephen C. Barker; Samuel Kelava; Wenjun Bu; Jingze Liu; Shan Gao
• Keywords: 0301 basic medicine; 572; DNA Copy Number Variations; High-Throughput Nucleotide Sequencing; Molecular Sequence Annotation; QH426-470; Polymerase Chain Reaction; Mitochondrial DNA; Precise annotation; Interspersed Repetitive Sequences; 03 medical and health sciences; 1311 Genetics; Genome, Mitochondrial; 1305 Biotechnology; Genetics; Animals; Short tandem repeat; Transposon; TP248.13-248.65; Tick; Biotechnology; Research Article; Dermacentor; Microsatellite Repeats

Abstract Background: In the present study, we used long-PCR amplification coupled with Next-Generation Sequencing (NGS) to obtain complete mitochondrial (mt) genomes of individual ticks and unprecedently performed precise annotation of these mt genomes. We aimed to: (1) to develop a simple, cost-effective and accurate method for the study of extremely high AT-content mt genomes within an individual animal containing miniscule DNA (e.g. Dermacentor silvarum); (2) to provide a high-quality reference genome for D. silvarum with precise annotation and also for future studies of other tick mt genomes; and (3) to detect and analyze mt DNA variation within an individual tick.Results: These annotations were confirmed by the PacBio full-length transcriptome data to cover both entire strands of the mitochondrial genomes without any gaps or overlaps. Moreover, two new and important findings were reported for the first time, contributing fundamental knowledge to mt biology. The first was the discovery of a transposon-like element that may eventually reveal much about mechanisms of gene rearrangements in mt genomes. Another finding was that Copy Number Variation (CNV) of Short Tandem Repeats (STRs) account for mitochondrial sequence diversity (heterogeneity) within an individual tick, insect, mouse or human, whereas SNPs were not detected. The CNV of STRs in the protein-coding genes resulted in frameshift mutations in the proteins, which can cause deleterious effects. Mitochondria containing these deleterious STR mutations accumulate in cells and can produce deleterious proteins. Conclusions: We proposed that the accumulation of CNV of STRs in mitochondria may cause aging or diseases. Future tests of the CNV of STRs hypothesis help to ultimately reveal the genetic basis of mitochondrial DNA variation and its consequences (e.g., aging and diseases) in animals. Our study will lead to the reconsideration of the importance of STRs and a unified study of CNV of STRs with longer and shorter repeat units (particularly polynucleotides) in both nuclear and mt genomes.