A large-scale genomic approach affords unprecedented resolution for the molecular epidemiology and evolutionary history of contagious caprine pleuropneumonia

Abstract

Contagious caprine pleuropneumonia (CCPP), caused by Mycoplasma capricolum subsp. capripneumoniae (Mccp), is a devastating disease of domestic goats and of some wild ungulate species. The disease is currently spreading in Africa and Asia and poses a serious threat to disease-free areas. A comprehensive view of the evolutionary history and dynamics of Mccp is essential to understand the epidemiology of CCPP. Yet, analysing the diversity of genetically monomorphic pathogens, such as Mccp, is complicated due to their low variability. In this study, the molecular epidemiology and evolution of CCPP was investigated using a large-scale genomic approach based on next-generation sequencing technologies, applied to a sample of strains representing the global distribution of this disease. A highly discriminatory multigene typing system was developed, allowing the differentiation of 24 haplotypes among 25 Mccp strains distributed in six genotyping groups, which showed some correlation with geographic origin. A Bayesian approach was used to infer the first robust phylogeny of the species and to date the principal events of its evolutionary history. The emergence of Mccp was estimated only at about 270 years ago, which explains the low genetic diversity of this species despite its high mutation rate, evaluated at 1.3 × 10(-6) substitutions per site per year. Finally, plausible scenarios were proposed to elucidate the evolution and dynamics of CCPP in Asia and Africa, though limited by the paucity of Mccp strains, particularly in Asia. This study shows how combining large-scale genomic data with spatial and temporal data makes it possible to obtain a comprehensive view of the epidemiology of CCPP, a precondition for the development of improved disease surveillance and control measures.

Figure 1

Haplotype network of Mycoplasma capricolum subsp. capripneumoniae. The median-joining network was reconstructed using NETWORK based on the alignment of 57 concatenated genes from 25 Mccp strains. The tree shows 24 haplotypes (nodes) resulting from 239 polymorphic positions including gaps. Different colours indicate the geographic origin of haplotypes.

Figure 2

Bayesian inference of Mycoplasma capricolum subsp. capripneumoniae evolutionary history. The Maximum Clade Credibility tree resulted from BEAST analysis of the alignment of concatenated sequences of 47 coding sequences from 25 Mccp strains. Bayesian posterior probabilities higher than 0.9 are represented by a white circle. Age estimates are displayed for relevant nodes with the 95% highest probability density intervals in brackets. The scale is given in years before present. The branch corresponding to the outgroup (California Kid) was shortened, as indicated by parallel bars.

Figure 3

Integration of genomic, geographic, historical and animal movement data to investigate the epidemiology of CCPP. The original location of each Mccp strain is indicated by a symbol, according to the corresponding genotyping group. The green arrows show major CCPP diffusion routes. The dates of the first clinical descriptions of the disease are indicated in red italics. Question marks are placed in areas from where no recent data is available.