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. 2016 Sep 23;11(9):e0162180.
doi: 10.1371/journal.pone.0162180. eCollection 2016.

Positive Selection Drives Rapid Evolution of the meq Oncogene of Marek's Disease Virus

Abinash Padhi  1 , Mark S Parcells  2
Affiliations

Positive Selection Drives Rapid Evolution of the meq Oncogene of Marek's Disease Virus

Abinash Padhi et al. PLoS One. .

Abstract

Marek's disease (MD), caused by Marek's disease virus (MDV), a poultry-borne alphaherpesvirus, is a devastating disease of poultry causing an estimated annual loss of one billion dollars to poultry producers, worldwide. Despite decades of control through vaccination, MDV field strains continue to emerge having increased virulence. The evolutionary mechanism driving the emergence of this continuum of strains to increased MDV virulence, however, remains largely enigmatic. Increase in MDV virulence has been associated with specific amino acid changes within the C-terminus domain of Mareks's EcoRI-Q (meq)-encoded oncoprotein. In this study, we sought to determine whether the meq gene has evolved adaptively and whether past vaccination efforts have had any significant effect on the reduction or increase of MDV diversity over time. Our analysis suggests that meq is estimated to be evolving at a much faster rate than most dsDNA viruses, and is comparable with the evolutionary rate of RNA viruses. Interestingly, most of the polymorphisms in meq gene appear to have evolved under positive selection and the time of divergence at the meq locus coincides with the period during which the poultry industry had undergone transitions in management practices including the introduction and widespread use of live attenuated vaccines. Our study has revealed that the decades-long use of vaccines did not reduce MDV diversity, but rather had a stimulating effect on the emergence of field strains with increased genetic diversity until the early 2000s. During the years 2004-2005, there was an abrupt decline in the genetic diversity of field isolates followed by a recovery from this bottleneck in the year 2010. Collectively, these data suggest that vaccination seems to not have had any effect on MDV eradication, but rather had a stimulating effect on MDV emergence through adaptation.

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Conflict of interest statement

The authors acknowledge no competing interests.

Figures

Fig 1
Fig 1. Maximum likelihood tree of MDV meq sequences.
Maximum likelihood tree inferred from meq gene complete nucleotide sequence data of 44 MDV isolates with known pathotypes are shown. Bars at right identify the phylogenetic clustering of pathotypes from different geographic regions. Bootstrap supports/posterior probabilities are mentioned at the base of the nodes. Nodes with high bootstraps/posterior probabilities (> 60/0.95) are indicated by clusters, C1-C5. Abbreviations: m: mild, att: attenuated, hv: high virulence, vv: very virulence, v: virulent, vv+: very virulent plus.
Fig 2
Fig 2. The root-to-tip genetic distance based on meq gene versus year of MDV isolation.
The regression coefficient (R2) estimates the fit of the data to a strict molecular clock by testing the degree of influence sampling time has over the amount of pairwise diversity in the data. This analysis suggests the presence of temporal structure for meq gene of MDV.
Fig 3
Fig 3. Maximum Clade Credibility (MCC) tree inferred from the Bayesian analysis of the MDV meq gene sequences.
The mean TMRCAs with confident intervals (above the nodes) and the posterior probabilities (below the nodes) are mentioned.
Fig 4
Fig 4. Bayesian skyline plot (BSP) inferred from the meq gene sequences.
The BSP above depicts the relative genetic diversity of MDV over time. The plot depicting MDV population had recovered from a recent bottleneck (~2005–2008).
Fig 5
Fig 5. Variable amino acid sites in meq genes.
Positively selected with posterior probability > 0.95 and sites with posterior probability between 0.90–0.95 are highlighted in black and grey colors, respectively.
See this image and copyright information in PMC

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