Residues encoded by PSC in human IgA1 Cα1, Cα2 and Cα3 domains.

<p>Residues encoded by PSC are highlighted in red (selected in mammals), black (selected in primates and mammals) or blue (selected in primates). Sites of interaction with studied ligands are indicated below the sequence according to the colour panel on the figure. Bur numbering is shown above.</p

Characterization of natural amino acid variation for each residue identified under positive selection in mammal IgA.

a<p>IgA1 Bur numbering.</p>b<p>amino acid characteristics: H- Hydrophilic, HY- Hydrophobic, +- positive, –negative, n-neutral.</p

Residues encoded by PSC in the three-dimensional structure of human IgA1 and their relationship to sites of biological interest.

<p>A, Model of human IgA1 (PBD ID 1iga) with residues encoded by PSC highlighted. The light chains are colored green and the heavy chains colored yellow. Positively selected positions are represented by red dots (selected in mammals), black dots (selected in primates and mammals) or blue dots (selected in primates). B to F, Human IgA1-Fc (PDB ID 1OW0) with residues critical for FcαRI interaction (B), pIgR interaction (C), SSL7 interaction (D), streptococci IgA binding proteins interaction (E), and <i>H. influenzae</i> type 2 IgA1 protease interaction (F) highlighted in cyan, orange, pink, purple and grey respectively. Positively selected positions are represented as in panel A. Differences between the Fc structures in A and B-F reflect the fact that the model of intact IgA1 in A is based on low resolution X-ray and neutron scattering modeled based on the X-ray crystal structure of IgG Fc (the closest structure available at the time of modeling), while B-F show an X-ray crystal structure of human IgA1-Fc solved as part of a complex with FcαRI (not shown).</p

Phylogenetic tests of positive selection in mammals.

a<p>Codons identified by more than one ML method are underlined.</p>b<p>ps = proportion of the sites under selection, ωs = estimated dN/dS of the sites under selection in M8.</p>c<p>Positively Selected Codons: only the codons identified by at least two of the ML methods were considered to be positively selected codons.</p

Characterization of natural amino acid variation for each residue identified under positive selection in primate IgA.

a<p>IgA1 Bur numbering.</p>b<p>amino acid characteristics: H- Hydrophilic, HY- Hydrophobic, +- positive, –negative, n-neutral.</p

Scalp topographies for the parieto-occipital ERPs components.

<p>The voltage topographies of the parieto-occipital components on the scalp are shown for Neutral (top row), Angry (middle row) and Happy (bottom row) congruent audiovisual conditions (face and voice) at 130, 180, and 270 ms.</p

Type-II cystatin gene cluster region overview.

<p>Organization of the <i>CST1</i>-<i>5</i> genes in human (<i>Homo sapiens</i>), chimpanzee (<i>Pan troglodytes</i>), orangutan (<i>Pongo abelii</i>), gorilla (<i>Gorilla gorilla</i>), rhesus monkey (<i>Macaca mulatta</i>), marmoset (<i>Callithrix jacchus</i>), rat (<i>Rattus norvegicus</i>), mouse (<i>Mus musculus</i>), pig (<i>Sus scrofa</i>), cattle (<i>Bos taurus</i>) and dog (<i>Canis lupus familiaris</i>). The transcriptional orientation of the genes is shown; the pseudogenes are highlighted in yellow (data from ENSEMBL and NCBI databases). The genes used in the subsequent analysis are highlighted in blue.</p

Evolution of C, D and S-Type Cystatins in Mammals: An Extensive Gene Duplication in Primates

<div><p>Cystatins are a family of inhibitors of cysteine peptidases that comprises the salivary cystatins (D and S-type cystatins) and cystatin C. These cystatins are encoded by a multigene family (<i>CST3</i>, <i>CST5</i>, <i>CST4</i>, <i>CST1</i> and <i>CST2</i>) organized in tandem in the human genome. Their presence and functional importance in human saliva has been reported, however the distribution of these proteins in other mammals is still unclear. Here, we performed a proteomic analysis of the saliva of several mammals and studied the evolution of this multigene family. The proteomic analysis detected S-type cystatins (S, SA, and SN) in human saliva and cystatin D in rat saliva. The evolutionary analysis showed that the cystatin C encoding gene is present in species of the most representative mammalian groups, i.e. Artiodactyla, Rodentia, Lagomorpha, Carnivora and Primates. On the other hand, D and S-type cystatins are mainly retrieved from Primates, and especially the evolution of S-type cystatins seems to be a dynamic process as seen in <i>Pongo abelii</i> genome where several copies of <i>CST1-like</i> gene (cystatin SN) were found. In Rodents, a group of cystatins previously identified as D and S has also evolved. Despite the high divergence of the amino acid sequence, their position in the phylogenetic tree and their genome organization suggests a common origin with those of the Primates. These results suggest that the D and S type cystatins have emerged before the mammalian radiation and were retained only in Primates and Rodents. Although the mechanisms driving the evolution of cystatins are unknown, it seems to be a dynamic process with several gene duplications evolving according to the birth-and-death model of evolution. The factors that led to the appearance of a group of saliva-specific cystatins in Primates and its rapid evolution remain undetermined, but may be associated with an adaptive advantage.</p></div

Phylogenetic tree inferred by using Maximum Likelihood (ML) and Bayesian inference (BI).

<p>TPM3+I+G was the best fitting mutation model. For ML 1000 bootstrap replicates were considered and for BI posterior probabilities were calculated; posterior probabilities (<b>bold</b>) over 0.95 and bootstrap confidence (<i>italic</i>) over 90% are considered valid support and are shown in the tree.</p

ERP waveforms to each condition at fronto-central electrodes.

<p>The fronto-central components N1, P200, N250 and P300 are shown at F1, Fz, F2, C1, Cz and C2 for the neutral (Black), happy (Red) and angry (Green) congruent audiovisual conditions (face and voice).</p