Population genomics has only recently been integrated into studies of infectious diseases. This is because DNA from parasites can be hard to obtain and many epidemiologists are not trained in population genetics. In the last five years, I have strived to combined population genomics, epidemiology, and ecology to study the human parasite Wuchereria bancrofti. Wuchereria bancrofti (Wb) is a nematode causing Lymphatic filariasis, affecting over 120 million people in 73 countries with 1.39 billion people living in Wb endemic regions.
In 2011, we started with only a single gene on the mitochondrial genome, COI, to study population structure in communities infected with Wb parasites (Small et al. 2013). We combined our estimates of migration and population structure with survey data collected from the same communities. We concluded that high connectivity between communities would make it difficult to eliminate Wb, unless all communities were treated simultaneously. We also identified a single mitochondrial lineage (denoted as a single unique haplotype) that was present in 95% of all Wb infections.
In 2015, after sequencing the whole mitochondrial genome of multiple Wb isolates (Ramesh et al. 2012), we used whole genome data from 15 individual Wb worms to publish the first population genomics study of Wb. This project used a larval stage of Wb that only occurs within mosquitoes; still we did not have enough DNA for traditional genome sequencing. We thus modified an available approach using Nextera chemistry (Illumina) and singe-cell whole genome amplification to perform genome sequencing (Small et al 2016).
From the genomic data, we made three novel insights into Wb life history. First, we confirmed a hypothesis that female Wb worms mate with multiple Wb male worms by utilizing a multiple-dimensional relationship statistics based on whole genome variation. We used this data to infer pedigree relationships between worms in our samples, allowing for the first time a non-invasive estimate of adult Wb worms in an infection. Second, we reconstructed the population history of Wb in Papua New Guinea. This included a hypothesis of migration rather than isolation in spreading Wb from SE Asia to Papua New Guinea and other Pacific Islands. Finally, we searched the Wb genomes for signs of natural selection against commonly used chemotherapeutic drugs. While we did not find any signs of emerging drug resistance, we did discover that a gene critical for Wb’s survival in the human host, macrophage-inhibitory-factor (MIF-1), was under directional selection. A previous experiment using Brugia malayi, which can be cultured in lab animals, demonstrated that MIF-1 proteins influence the movement of macrophages in vitro (Pastrana et al. 1998. Infection and Immunity. vol. 66 no. 12 5955-5963). Future studies of this gene and its natural genetic variation will aid in Wb control and inform on the larger immunological landscape of parasite and the human immune system.