Multiple sequence alignment showing shared and group-specific motifs between the Agouti-like sequences.

<p>We include sequences that are previously published or already known for <i>AgRP</i> and <i>ASIP</i>-like clusters. The alignment includes the newly identified Agouti-like sequences in arthropods and in fungi. The important C-x(6)-C and the C-x(5,6)-C motif regions are shown above the alignment. The sequences that have the C-x(6)-C and C-x(5)-C motifs are distinguished with red and black dotted rectangular boxes, respectively. The residues that are conserved between the novel sequences and the different groups are shown with black rectangular boxes. The sequences that belong to different lineages are indicated with the colored line segments at the left of the alignment.</p

Hough transform comparison of synteny between Hsa 8, 60–100 Mb, and Ola 17 and 20.

<p>Hough transform comparison of synteny between Hsa 8, 60–100 Mb, and Ola 17 and 20.</p

Phylogenetic analysis of Agouti-like sequences.

<p>The unrooted maximum likelihood phylogenetic tree of Agouti-like sequences. Robustness of the nodes is tested with the posterior probabilities based on MCMC analysis as implemented in the MrBayes program. Both bootstrap (out of 500 replicates) and the posterior probability support were given in italics for the significant nodes. The posterior probability (1) of the A2 node is highlighted in red color. The tree is rooted on the node that clustered the consensus sequences, which serves as out-group.The tree shows that <i>A2</i> is likely to have branched from <i>ASIP1</i>.</p

Conserved synteny dot plots derived from the Synteny Database [<b>17</b>].

<p>(A–C) Conserved synteny dot plots derived from the Synteny Database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040982#pone.0040982-Catchen1" target="_blank">[17]</a>. (A) The zebrafish <i>AgRP2</i> region on Dre 2 (red box) shares conserved syntenies with neither the zebrafish <i>ASIP1</i> region (Dre 6) nor with the human <i>ASIP</i> region (Hsa 20). (B) The <i>AgRP2</i> and <i>ASIP2</i> regions in medaka and other teleosts share conserved synteny with each other and with a region on human Hsa10, including several <i>AgRP2</i>- and <i>ASIP2</i>-neighboring genes. (C) Analysis of the human genome shows that the <i>AgRP</i> region on Hsa16 shows more paralogous connections to the inferred <i>ASIP2</i> region on Hsa 8 than to the ASIP region on Hsa 20 (183 vs. 82 genes, respectively, not restricting Y-axis chromosomal regions).</p

Two-dimensional representation of the similarity relationships between the structure models of A1 and A2 inhibitor cysteine knots, as obtained by non-metric multidimensional scaling.

<p>The MDS fit measures (s-stress  = 0.14, RSQ = 0.95) indicate that the inter-model distances in this configuration reflect well the original inter-model dissimilarity values. The figure is generated by a Perl script that outputs support vector graphics. The figure shows that AgRP2 is more ASIP-like, and ASIP2 more AgRP-like, The shift of the A2 points towards ASIP agrees with the Mr. Bayes phylogram. Ptr Plt-VI is more AgRP-like.</p

Visual representation of the sampling process of the human genome.

<p>Visual representation of the sampling process of the human genome, where the x-axis represents the current sample size and the y-axis the frequency of windows that are characterized as “positive” hits against either Ola 17 or Ola 20. For each placed 40 Mb-sized window, we characterize the window as being a positive hit to either medaka chromosome 17 or 20, if it contains more orthologues (more synteny) with Ola 17 or Ola 20, and human chromosome 8, region 60–100 Mb. The error bars represent a 95% confidence interval that depends on the sample size; if the lower limit of a 95% confidence interval is negative, it is shaded on the mean. The sampling process was terminated at N = 100 and N = 500, for medaka chromosome 17 and 20, respectively. The mean frequencies and 95% confidence intervals are, at the termination points: f = 0.1000 for medaka chromosome 17 (95% CI: 0.0412−0.1588); f = 0.0180 for medaka chromosome 20 (95% CI: 0.0063−0.0297). We use a log scale for ease of reading.</p

Cysteine knots in spider toxins.

1)<p>The species that contains Hainantoxin-1.3.</p>2)<p>The species that contains Guangxiensistoxin.</p