Variable amino acid sites in <i>meq</i> genes.

<p>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.</p

Bayesian skyline plot (BSP) inferred from the <i>meq</i> gene sequences.

<p>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).</p

Bayesian estimates of the evolutionary rate and TMRCAs (in year) inferred from the MDV <i>meq</i> gene.

<p>Bayesian estimates of the evolutionary rate and TMRCAs (in year) inferred from the MDV <i>meq</i> gene.</p

Positive Selection Drives Rapid Evolution of the <i>meq</i> Oncogene of Marek’s Disease Virus

<div><p>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 (<i>meq</i>)-encoded oncoprotein. In this study, we sought to determine whether the <i>meq</i> 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 <i>meq</i> 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 <i>meq</i> gene appear to have evolved under positive selection and the time of divergence at the <i>meq</i> 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.</p></div

The root-to-tip genetic distance based on <i>meq</i> gene versus year of MDV isolation.

<p>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 <i>meq</i> gene of MDV.</p

Positively selected sites are shown as detected by REL and FUBAR methods.

<p>Positively selected sites are shown as detected by REL and FUBAR methods.</p

Maximum Clade Credibility (MCC) tree inferred from the Bayesian analysis of the MDV <i>meq</i> gene sequences.

<p>The mean TMRCAs with confident intervals (above the nodes) and the posterior probabilities (below the nodes) are mentioned.</p