Several PARP genes are evolving under positive selection.

<p>(A) Schematic domain structures of human PARP proteins are shown (not to scale). Numbers to the bottom right of the protein schematic indicate the total length, in amino acids, of each protein. BRCT: BRCA1 C-terminus domain; VIT: vault inter-trypsin domain; vWA: von Willebrand factor type A; MVP-BD: major vault protein binding domain. ¹PARPs are categorized as either poly-ADP-ribosyltransferases (Poly-), mono-ADP-ribosyltransferases (Mono-) or inactive based on presence of conserved motifs and, when available, data using enzymatic assays <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004403#pgen.1004403-Hottiger1" target="_blank">[4]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004403#pgen.1004403-Gibson1" target="_blank">[6]</a>. ²PARP9 and PARP13 lack one or more catalytic residues conserved in all other PARPs and are therefore predicted to lack catalytic activity, although it is unknown whether they still bind ADP-ribose or ADP-ribosylated proteins <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004403#pgen.1004403-Hottiger1" target="_blank">[4]</a>. (B) Results of maximum likelihood tests for positive selection. The five PARP genes showing strong signatures of positive selection are shown in red. Shown at left are values derived from PAML indicating twice the log difference between an evolutionary model that allows positive selection (M8) versus a model that disallows position selection (M8a). P-values indicate whether the model that allows positive selection better fits the data. PARRIS-derived LRT (likelihood ratio test) values also report the difference between the log-likelihood values for a model allowing positive selection versus a model that does not. Using seven orthologs in PARRIS only gave a statistically significant p-value (<0.01) for <i>PARP4</i> and <i>PARP13</i>, however analysis of additional sequences of <i>PARP9</i>, <i>14</i> and <i>15</i> found that these genes also met statistical significance (see Results). Additional analyses are reported in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004403#pgen.1004403.s004" target="_blank">Figure S1</a>.