Examples of parallel adaptations following host shifts.

<p>(A) Parallel genetic changes in five replicate lines of Hibiscus chlorotic ring spot virus. The white boxes represent the viral genome, and the coloured blocks represent mutations. The virus naturally infects <i>Hibiscus</i> plants, but following five passages in an alternate host, (<i>Chenopodium quinoa</i>) the same eight mutations repeatedly occur <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004395#ppat.1004395-Liang1" target="_blank">[57]</a>. (B) Parallel genetic changes in codon 30 of the gag gene (Met to Arg) following three independent transfers of SIVcpz into humans <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004395#ppat.1004395-Wain1" target="_blank">[59]</a>. When a chimp was subsequently infected with HIV-1, the residue reverted back to Met. The coloured blocks represent either a Met (yellow) or Arg (blue) at codon position 30 in the HIV gag gene. (C) Parallel changes in protein function following independent transfers of SIVs from chimpanzees (HIV-1) and sooty mangabeys (HIV-2) into humans. SIV Nef protein does not antagonise tetherin in humans, and so other HIV proteins have evolved the ability to antagonise tetherin <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004395#ppat.1004395-Sauter1" target="_blank">[64]</a>. The exception to this is HIV-1 group O viruses, which do not appear to have evolved anti-tetherin activity. In HIV-1 group N viruses the evolution of anti-tetherin activity in Vpu may have come at a cost, as Vpu no longer degrades CD4 receptors to aid the release of viral particles <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004395#ppat.1004395-Malim1" target="_blank">[61]</a>. The coloured gene names in the schematic represent the gene that provides the anti-tetherin function in that host and viral lineage.</p

Two ways in which host relatedness may effect a pathogen's ability to host shift.

<p>The bars at the tips of the trees show a measure of pathogen infection success, with the bar in red representing the pathogen's natural host species. (A) The pathogen is less successful in host clades more distantly related to its natural host. (B) “Patches” of highly susceptible—or highly resistant—clades of hosts, may be scattered across the host phylogeny independently from their distance from the natural host. All of the species in the clade labelled “a” are equally distantly related from the pathogen's natural host. However, the species in the clade marked “b” are highly susceptible, despite being distantly related to the natural host.</p

Factors that evolutionary theory predicts will affect the likelihood that the correct set of mutations will arise to adapt a pathogen to a new host.

<p>Such theoretical predictions as listed above have been shown to be important for adaptation per se <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004395#ppat.1004395-Smith1" target="_blank">[87]</a>, and these population genetic parameters will also be important in determining the ability of a pathogen to adapt to a novel host.</p><p>Factors that evolutionary theory predicts will affect the likelihood that the correct set of mutations will arise to adapt a pathogen to a new host.</p

Selective advantages when the substitution is absent at the start of infection.

<p>A) The selective advantage required to achieve 50% (black) prevalence of the adaptive substitution within the host after a certain number of days of infection in a situation where the substitution is not present in the infecting virus population (results for 10% and 90% shown in grey). B) The proportion of mutant observed after 3 (dark blue), 6 (blue), 9 (pink), 12 (red) and 15 (dark red) days of infection for a range of selective advantages. The grey bar indicates 50% prevalence.</p

Quantifying the selective advantage as a function of substitution prevalence at the start of infection and infection duration.

<p>The minimum selective advantage necessary to reach 50% prevalence in the human host is displayed in color as a function of days of infection (y-axis) and mutant proportion at start of infection (x-axis). Selective advantages of 2.5 and 1 represent the upper and lower bounds of the color bar. The selective advantage exceeds 2.5 for early time points (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076047#pone-0076047-g001" target="_blank">Figure 1A</a>), but for clarity, a threshold was used here. For starting prevalences of >50% no selective advantage is required.</p

B/Yamagata sequence data

Tab-delimited text file giving sequence accession numbers for seasonal B/Yamagata influenza viruses isolated between 1987 and 2011. Sequences come from both the Influenza Research Database (http://www.fludb.org/) and the EpiFlu Database that is part of GISAID (http://www.gisaid.org/)

B/Victoria sequence data

Tab-delimited text file giving sequence accession numbers for seasonal B/Victoria influenza viruses isolated between 1986 and 2011. Sequences come from both the Influenza Research Database (http://www.fludb.org/) and the EpiFlu Database that is part of GISAID (http://www.gisaid.org/)

A/H3N2 HI data

Tab-delimited text file giving hemagglutination inhibition (HI) titers for seasonal A/H3N2 influenza viruses and ferret antisera isolated between 1968 and 2011. The virus strain used in the HI assay as well as the specific virus isolate are listed. The strain used as antiserum and the specific antiserum isolate are also listed. Data was compiled from multiple sources, listed in the sources column and fully referenced in the publication

B/Yamagata HI data

Tab-delimited text file giving hemagglutination inhibition (HI) titers for seasonal B/Yamagata influenza viruses and ferret antisera isolated between 1987 and 2011. The virus strain used in the HI assay as well as the specific virus isolate are listed. The strain used as antiserum and the specific antiserum isolate are also listed. Data was compiled from multiple sources, listed in the sources column and fully referenced in the publication

A/H3N2 sequence data

Tab-delimited text file giving sequence accession numbers for seasonal A/H3N2 influenza viruses isolated between 1968 and 2011. Sequences come from both the Influenza Research Database (http://www.fludb.org/) and the EpiFlu Database that is part of GISAID (http://www.gisaid.org/)