Abstract
Lymphatic filariasis is a neglected parasitic disease that is a leading cause of long-term disability. Information obtained from genome sequencing of filarial worm can help us identify systems in the worm that are likely to be useful for novel drug design. Brugia (B.) malayi is still the only lymphatic-dwelling filarial parasite with a nearly complete, fully annotated, and published genome. However, most previous studies were based on the FR3 strain of B. malayi, which originally was isolated from a human patient, and was adapted to the rodent model, then maintained in laboratories for more than 60 years. It is uncertain whether genetic variation exists, thus, sequencing of clinical isolates of lymphatic dwelling filarial parasites is a high priority. Here, we report for the first time the complete mitochondrial genome of B. malayi microfilariae from clinical isolate. Complete mitochondrial (mt) genome of the microfilariae isolated from a blood sample taken from a Thai subject living in Narathiwat Province, which is an endemic area of brugian filariasis, was assembled with sequencing reads obtained by Illumina sequencing. Gene annotation, phylogenetic analysis and single nucleotide polymorphism (SNP) were deployed. A complete 13,658-bp mt genome of B. malayi microfilaria was obtained, and it shows 68x coverage. Based on gene annotation, the mt genome consists of 12 protein-coding, two rRNA, and 23 tRNA genes. Phylogenetic analysis using all protein sequences of DNA sequences of mt genome or cytochrome c oxidase subunit I (COX1) revealed a close relationship among three lymphatic filariae (i.e., B. timori, zoonotic B. pahangi, and Wuchereria spp.). The SNPs in the COX1 gene can differentiate microfilariae of B. malayi in human from those found in canine. Furthermore, the number, order and transcription, and direction of B. malayi microfilariae mitochondrial genes were the same as those found in the FR3 strain of B. malayi. The comparison on mitochondrial genome of B. malayi could have important implications on the development of a new intervention or vaccine to treat or prevent this disease in endemic areas/regions around the world.
Highlights
Lymphatic filariasis is an often-neglected tropical disease that adversely affects society and economics due to associated high morbidity, social stigmatization, and inability to work
The extra and duplicated lysine (K) tRNA was annotated in BM2 mt (Figure 1F), while the DNA sequence of this lysine (K) tRNA identically exists in the mitochondrial sequence of B. malayi FR3 strain, but did not annotated
The trnK-UUU was predicted at position 4,561–4,615 of the BM2 mt genome which is a region that overlaps with cytochrome b (COB) (4,578–5,664), and the sequence of this trnK-UUU identically existed in the mitochondrial genome of FR3 but not annotated
Summary
Lymphatic filariasis is an often-neglected tropical disease that adversely affects society and economics due to associated high morbidity, social stigmatization, and inability to work. The primary pillar of this program is mass drug administration of diethylcarbamazine, albendazole, and ivermectin. Antifilarial drug resistance has emerged (Schwab et al, 2005; Cobo, 2016), which presents a threat to the success of this treatment and elimination program. Genetic mutation of the parasite due to mass drug administration for several years is hypothesized to be an underlying cause of drug resistance (Schwab et al, 2005). To cope with drug resistance and to pave the way for the development of more effective drugs, data specific to the genetic variability of this parasite among different geographic areas are needed
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