Global selective sweep of a highly inbred genome of the cattle parasite Neospora caninum

Asis Khan; Ayako Wendy Fujita; Nadine Randle; Javier Regidor-Cerrillo; Jahangheer S. Shaik; Kui Shen; Andrew J. Oler; Mariam Quinones; Sophia M. Latham; Bartholomew D. Akanmori; Sarah Cleaveland; Elisabeth A. Innes; Una Ryan; Jan Šlapeta; Gereon Schares; Luis M. Ortega-Mora; Jitender P. Dubey; Jonathan M. Wastling; Michael E. Grigg

doi:10.1073/pnas.1913531116

New Research In

Contributed by Jitender P. Dubey, September 19, 2019 (sent for review August 6, 2019; reviewed by Damer P. Blake and Joseph Heitman)

This article has a Correction. Please see:

Correction for Khan et al., Global selective sweep of a highly inbred genome of the cattle parasite Neospora caninum - December 09, 2019

Significance

The parasite Neospora caninum has a worldwide distribution and causes fetal loss in livestock. It is transmitted in cows vertically (from mother to fetus), and in some herds nearly all cattle are infected. We genotyped Neospora strains isolated from an array of infected hosts (dogs, cattle, deer, horse, rhinoceros) and observed a single, highly inbred genome that has swept globally. At first glance, data support vertical transmission as a primary mode for the expansion of the parasite genome; however, genome-level analyses identified large introgression blocks of a distinct ancestry that has recombined into the genome, consistent with a unisexual expansion model. The successful genome appears to have piggy-backed on the expansion of European cattle breeds that have been exported globally.

Abstract

Neospora caninum, a cyst-forming apicomplexan parasite, is a leading cause of neuromuscular diseases in dogs as well as fetal abortion in cattle worldwide. The importance of the domestic and sylvatic life cycles of Neospora, and the role of vertical transmission in the expansion and transmission of infection in cattle, is not sufficiently understood. To elucidate the population genomics of Neospora, we genotyped 50 isolates collected worldwide from a wide range of hosts using 19 linked and unlinked genetic markers. Phylogenetic analysis and genetic distance indices resolved a single genotype of N. caninum. Whole-genome sequencing of 7 isolates from 2 different continents identified high linkage disequilibrium, significant structural variation, but only limited polymorphism genome-wide, with only 5,766 biallelic single nucleotide polymorphisms (SNPs) total. Greater than half of these SNPs (∼3,000) clustered into 6 distinct haploblocks and each block possessed limited allelic diversity (with only 4 to 6 haplotypes resolved at each cluster). Importantly, the alleles at each haploblock had independently segregated across the strains sequenced, supporting a unisexual expansion model that is mosaic at 6 genomic blocks. Integrating seroprevalence data from African cattle, our data support a global selective sweep of a highly inbred livestock pathogen that originated within European dairy stock and expanded transcontinentally via unisexual mating and vertical transmission very recently, likely the result of human activities, including recurrent migration, domestication, and breed development of bovid and canid hosts within similar proximities.

Footnotes

↵¹A.W.F. and N.R. contributed equally to this work.
↵²Present address: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
↵³To whom correspondence may be addressed. Email: jitender.dubey{at}usda.gov or griggm{at}niaid.nih.gov.

Author contributions: A.W.F., S.M.L., J.P.D., J.M.W., and M.E.G. designed research; A.K., A.W.F., N.R., and S.M.L. performed research; A.K., J.R.-C., J.S.S., K.S., A.J.O., M.Q., S.M.L., B.D.A., S.C., E.A.I., U.R., J.Š., G.S., L.M.O.-M., J.P.D., J.M.W., and M.E.G. contributed new reagents/analytic tools; A.K., A.W.F., N.R., and M.E.G. analyzed data; and A.K., J.P.D., J.M.W., and M.E.G. wrote the paper.
Reviewers: D.P.B., Royal Veterinary College; and J.H., Duke University.
The authors declare no competing interest.
Data deposition: Sequence reads from the Illumina sequences were deposited in the NCBI Sequence Read Archive, https://www.ncbi.nlm.nih.gov, under BioProject number PRJNA534109 (accession nos. SRX5723126 [NC1], SRX5723132 [NC2], SRX5723128 [NC3], SRX5723130 [NC9], SRX5723131 [NcSP1], SRX5723129 [NcSP7], and SRX5723127 [NhOregon]).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1913531116/-/DCSupplemental.