X-treme loss of sequence diversity linked to neo-X chromosomes in filarial nematodes.

John Mattick,Andrew Steven,Mohd Shahab,Lisa Sadzewicz,Atiporn Saeung,Wanpen Chaicumpa,Silvia Libro,Matthew Chung,Nikhil Kumar,Luke J Tallon ,Robin E Bromley ,Andrew R Moorhead ,Darren Cook,Shailja Misra‐Bhattacharya ,Mark J Taylor ,Mohammad Behram Khan,Michelle L Michalski ,Ramakrishna U Rao ,Joseph D Turner ,Jeremy M Foster ,Yee Ling Lau ,Benjamin C Sparklin ,Julie C Dunning Hotopp

doi:10.1371/journal.pntd.0009838

Abstract

The sequence diversity of natural and laboratory populations of Brugia pahangi and Brugia malayi was assessed with Illumina resequencing followed by mapping in order to identify single nucleotide variants and insertions/deletions. In natural and laboratory Brugia populations, there is a lack of sequence diversity on chromosome X relative to the autosomes (πX/πA = 0.2), which is lower than the expected (πX/πA = 0.75). A reduction in diversity is also observed in other filarial nematodes with neo-X chromosome fusions in the genera Onchocerca and Wuchereria, but not those without neo-X chromosome fusions in the genera Loa and Dirofilaria. In the species with neo-X chromosome fusions, chromosome X is abnormally large, containing a third of the genetic material such that a sizable portion of the genome is lacking sequence diversity. Such profound differences in genetic diversity can be consequential, having been associated with drug resistance and adaptability, with the potential to affect filarial eradication.

Highlights

IntroductionWuchereria bancrofti, and Brugia timori are filarial nematodes (roundworms) that are responsible for lymphatic filariasis in humans with almost a billion people receiving >7.7 billion doses of treatment through lymphatic filariasis elimination efforts [1]
Brugia malayi, Wuchereria bancrofti, and Brugia timori are filarial nematodes that are responsible for lymphatic filariasis in humans with almost a billion people receiving >7.7 billion doses of treatment through lymphatic filariasis elimination efforts [1]
In addition to lymphatic filariasis, filarial nematodes are responsible for other diseases of medical and veterinary important, including human onchocerciasis [7] caused by the filarial nematode Onchocerca volvulus, human loiasis [8] caused by Loa loa, and dog and cat heartworm caused by Dirofilaria immitis [9]

Summary

Introduction

Wuchereria bancrofti, and Brugia timori are filarial nematodes (roundworms) that are responsible for lymphatic filariasis in humans with almost a billion people receiving >7.7 billion doses of treatment through lymphatic filariasis elimination efforts [1]. Of the three filarial species responsible for human lymphatic filariasis, only a subset of B. malayi strains can be maintained in small animals in the laboratory, a prerequisite for rigorous laboratory-based studies. These laboratory populations are critical to our understanding of filarial biology, and are commonly used for anti-filarial drug trials [3]. Brugia pahangi can be maintained in a laboratory life cycle, infects cats and dogs, and is occasionally zoonotic. B. pahangi and B. malayi use mosquito insect vectors and can co-infect dogs and cats [4]. In addition to lymphatic filariasis, filarial nematodes are responsible for other diseases of medical and veterinary important, including human onchocerciasis [7] caused by the filarial nematode Onchocerca volvulus, human loiasis [8] caused by Loa loa, and dog and cat heartworm caused by Dirofilaria immitis [9]

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