Assemblage of an adenovirus DNA-dependent-DNA polymerases (DdDp or cores) maximum likelihood tree (inferred with <i>phyml</i>) rooted at the Siadenovirus (left) and a phenogram clustered with the neighbor-joining method implemented in the Weighbor program for adenovirus “core-less” genomes, <i>i.e.</i>, without the DdDp (including satellite functions) rooted at the node connecting the Atadenovirus to the Siadenovirus (right).

<p>Nodes encircled by black dots indicate codivergence events. Values near the nodes of the DdDp indicate the number of times that each tree component was observed during 500 non-parametric bootstrap maximum likelihood iterations with <i>phyml</i>, value between parenthesis are the posterior Bayesian probability of the node estimated with MrBayes. Nodes encircled by black dots indicate codivergence events estimated with the TreeMap program.</p

Plot showing a positive correlation (<i>r²</i> = 0.84) between the average genome in each viral family versus the ratio (Cd/nCd) of codivergence (Cd) over non-codivergence (nCd) events.

<p>The ratio is a measure of the linkage disequilibrium between the core polymerase gene and the remainder of the genome. Larger genomes tend to diverge in a more concerted fashion, whereas smaller genomes show greater independence in genetic segregation among constituents of their genomes. Hence smaller viral genomes behave somewhat like a mutualistic network, with the core acting as a host and the accessory satellites as symbionts.</p

Gene accretion and loss in the baculovirus (5A and 5B) and poxvirus (5C and 5D).

<p>Solid lines are least squares linear regression to the data. Dashed lines bound 95% confidence intervals on the mean regression lines. Rates of gene gain are far higher than rates of gene loss. The number of gain and loss events for baculovirus was estimated with MacClade and for poxvirus was obtained from McLysaght <i>et al.</i>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003500#pone.0003500-McLysaght1" target="_blank">[2]</a>. The regression indicate a positive dependence on the number of gene gains on branch length in the tree for the complete genomes, whereas loss events were less frequent and had no significant dependence on branch length (as indicated by the low correlation coefficients on the shallow gradients). The data suggested that the process of gene gain in these 2 viral families is temporally organized, since genetic distance (branch lengths) is proportional to time. For both loss and gain the distribution of gain and loss departs from a simple exponential model predicted by the branch lengths. A similar accretion process of auxiliary gene functions in large DNA viruses has been observed for herpesvirus <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003500#pone.0003500-Montague1" target="_blank">[1]</a>.</p

Assemblage of poxvirus trees rooted with the insect-infecting entomopoxvirus and a phenogram clustered with the neighbor-joining method implemented in the Weighbor program for poxvirus “core-less” genomes, <i>i.e.</i>, without the DdDp (including satellite functions).

<p>All major groups of posxvirus were recovered. Nodes encircled by black dots indicate co-divergence events. Values near the nodes of the DdDp indicate the number of times that each tree component was observed during 500 non-parametric bootstrap maximum likelihood iterations with <i>phyml</i>, value between parenthesis are the posterior Bayesian probability of the node estimated with MrBayes. Nodes encircled by black dots indicate codivergence events estimated with the TreeMap program.</p

Sources, names, labels and sizes for complete genomes from selected representatives from four DNA virus families.

<p>Sources, names, labels and sizes for complete genomes from selected representatives from four DNA virus families.</p

Assemblage of a herpesvirus DNA-dependent-DNA polymerase (DdDp or cores) maximum likelihood tree rooted with the Ictalurid virus (IcHV-1) infecting the Channel catfish (right) and a phenogram clustered with the neighbor-joining method implemented in the Weighbor program for herpesvirus “core-less” genomes, <i>i.e.</i>, without the DdDp (including satellite functions) rooted at the Alpha-herpesvirus (Alphaherpesvirinae) that infect birds and mammals (right).

<p>In spite of the IcHV-1 being distantly related to the herpesvirus and of questionable membership in the Herpesviridae family, it shares several satellite functions with the Beta and Gammaherpesvirinae infecting tetrapods. Nodes encircled by black dots indicate co-divergence events. Values near the nodes of the DdDp indicate the number of times that each tree component was observed during 500 non-parametric bootstrap maximum likelihood iterations with <i>phyml</i>, value between parenthesis are the posterior Bayesian probability of the node estimated with MrBayes. Nodes encircled by black dots indicate codivergence events estimated with the TreeMap program.</p

Codivergence events of DdDp (core) and “core-less” genomes (satellite) assemblages for four DNA viral families.

¶<p>The reconstructions of codivergence events were obtained by minimizing the numbers of duplication, exchange and sorting events, inferred with the TreeMap program v 1.0, and evaluated against 10 thousand random assemblages to obtain a number of codivergent events expected by chance, which was expressed as probability of the observed the number codivergent events shown in the <b><i>p</i></b> column.</p>§<p>Assemblages (tanglegrams) for each virus family included trees for the core (DdDp) reconstructed with maximum likelihood (ML) and parsimony (MP) and phenomes for satellite functions (core-less genomes) using the Median and Mean distances. Cd/nCd (last column) shows the ratio of codivergence (Cd) to the sum of non-codivergence (nCd) events for each viral family.</p

Phylogenetic Tree for DENV-4 Samples from Manaus, Brazil.

<p>The tree was inferred with the maximum likelihood criterion implemented in the program GARLI v0.95 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000390#pntd.0000390-Zwickl1" target="_blank">[8]</a>. Node support was evaluated with 100 independent runs with GARLI (percent values above branches), 500 non-parametric bootstrap replicates with PhyML <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000390#pntd.0000390-Guindon1" target="_blank">[9]</a> (percent values in between brackets below branches), and the posterior probability from the maximum credibility tree among 2,000 trees obtained after running 20 million generations in 15 chains with the parallel implementation of MrBayes v3.0B4 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000390#pntd.0000390-Ronquist1" target="_blank">[10]</a> (in bold to the right of the critical nodes). Genotypes II (yellow) and III (green) lineages were collapsed for clarity. The high support values are indicative of the membership in genotype I, but have to be taken cautiously since only 390 bp of the prM-core junction were reported (for more details, see the open-access paper by Figueiredo et al. <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000390#pntd.0000390-Figueiredo1" target="_blank">[4]</a>).</p

Does adaptation to vertebrate codon usage relate to flavivirus emergence potential?

<div><p>Codon adaptation index (CAI) is a measure of synonymous codon usage biases given a usage reference. Through mutation, selection, and drift, viruses can optimize their replication efficiency and produce more offspring, which could increase the chance of secondary transmission. To evaluate how higher CAI towards the host has been associated with higher viral titers, we explored temporal trends of several historic and extensively sequenced zoonotic flaviviruses and relationships within the genus itself. To showcase evolutionary and epidemiological relationships associated with silent, adaptive synonymous changes of viruses, we used codon usage tables from human housekeeping and antiviral immune genes, as well as tables from arthropod vectors and vertebrate species involved in the flavivirus maintenance cycle. We argue that temporal trends of CAI changes could lead to a better understanding of zoonotic emergences, evolutionary dynamics, and host adaptation. CAI appears to help illustrate historically relevant trends of well-characterized viruses, in different viral species and genetic diversity within a single species. CAI can be a useful tool together with <i>in vivo</i> and <i>in vitro</i> kinetics, phylodynamics, and additional functional genomics studies to better understand species trafficking and viral emergence in a new host.</p></div

CAI and phylodynamics of West Nile virus lineage 2 sequences.

<p>A) Bayesian maximum clade credibility tree representing a time scaled phylogeny of a WNV lineage 2 polyprotein sequences. Bayesian posterior probabilities > 0.9 are marked with an asterisk at major nodes. Averages for the European epidemic lineage (yellow bar) and a 2^nd European lineage (highlighted in red) are shown. B) Malthusian fitness (<i>Wm</i>) was calculated from 2004–2014, and compared to LOESS trend lines generated from CAI values to the codon usages of C) human house-keeping genes, D) human immune/antiviral genes, E) pigeon (Columba livia) genes, and F) mosquito (<i>Culex pipiens</i>) genes. G) The Spearman’s rank correlation test was used to test if there were any correlations between the 2010 to 2012 CAI increase in mosquitoes and the CAI increase in vertebrate species from 2012–2014, as well as Wm. The ΔCAI, Δ<i>Wm</i> and <i>rho</i> are shown for clarity. # = for all correlations, <i>p</i>-values were < 0.05.</p