Molecular epidemiology, phylogeny and evolution of the filarial nematode Wuchereria bancrofti

Abstract

Wuchereria bancrofti (Wb) is the most widely distributed of the three nematodes known to cause lymphatic filariasis (LF), the other two being Brugia malayi and B. timori. Current tools available to monitor LF are limited to diagnostic tests targeting DNA repeats, filarial antigens, and anti-filarial antibodies. While these tools are useful for detection and surveillance, elimination programs have yet to take full advantage of molecular typing for inferring infection history, strain fingerprinting, and evolution. To date, molecular typing approaches have included whole mitochondrial genomes, genotyping, targeted sequencing, and random amplified polymorphic DNA (RAPDs). These studies have revealed much about Wb biology. For example, in one study in Papua New Guinea researchers identified 5 major strains that were widespread and many minor strains some of which exhibit geographic stratification. Genome data, while rare, has been utilized to reconstruct evolutionary relationships among taxa of the Onchocercidae (the clade of filarial nematodes) and identify gene synteny. Their phylogeny reveals that speciation from the common ancestor of both B. malayi and Wb occurred around 5–6 millions years ago with shared ancestry to other filarial nematodes as recent as 15 million years ago. These discoveries hold promise for gene discovery and identifying drug targets in species that are more amenable to in vivo experiments. Continued technological developments in whole genome sequencing and data analysis will likely replace many other forms of molecular typing, multiplying the amount of data available on population structure, genetic diversity, and phylogenetics. Once widely available, the addition of population genetic data from genomic studies should hasten the elimination of LF parasites like Wb.

Genomic Epidemiology in Filarial Nematodes: Transforming the Basis for Elimination Program Decisions

“…Genetic structure is the result of movement of parasites within, but not between, transmission zones: parasites within a transmission zone interbreed and are genetically more similar to each other than to parasites in another transmission zone, with whom they do not interbreed. The likelihood that parasites are from the same transmission zone, and thus likelihood of parasite transmission between two locations (invasion), can therefore be inferred from the degree of genetic relatedness between them (e.g., Blouin et al, 1995;Nadler, 1995;Criscione and Blouin, 2004;Small et al, 2014). Statistically significant genetic differentiation at neutral loci (i.e., loci which do not affect a phenotype subject to selection pressure) between two parasite samples indicates that they originate from two separate transmission zones ( Figure 4).…”

The drug target genes show higher evolutionary conservation than non-target genes

“…Previous researches have shown that evolutionary features offer fresh views to many important fields that are related to drug discovery, including immunology [ 6 ], physiology [ 7 , 8 ], epidemiology [ 9 ] and neurosciences [ 10 ]. Wang et al [ 11 ] conducted an analysis and showed that some targeted genes shared common evolutionary features, which suggested that evolutionary information might provide novel insights for characterizing drug targets from new perspectives.…”

Human Migration and the Spread of the Nematode ParasiteWuchereria bancrofti

“…Ten PacBio SMRT cells were run for an estimated coverage of 20-40X. Whole genomes were aligned using progressiveCactus (https://github.com/glennhickey/progressiveCactus) with a guide tree reconstructed from whole mitochondrial genomes [Small et al, 2014]. Ragout [Kolmogorov et al, 2014] was run allowing for repeat resolution with scaffolds named according to B. malayi reference genome.…”