Fold Duplication and Family Counts of Ancient Folds

<p>Ancient SCOP folds were divided into a number of bins according to the number of families that they contain (<i>x</i>-axis). The maximum number of times each fold is reused in the same protein was counted. The mean count for each bin is shown for human, mouse, and yeast proteins. As the number of families in a SCOP fold increases, the maximum number of times the fold is duplicated in proteins also tends to increase. The differences in magnitude of duplication between folds with one family and folds with more than one family are significant (MW-test, KS-test: <i>p <</i> 0.01). The differences in fold duplication between human, mouse, and yeast are larger for folds with larger numbers of families. The differences between folds with one family and folds with more than one family with respect to mammals and yeast are significant (MW-test: <i>p <</i> 0.05; KS-test: <i>p <</i> 0.001). The significance of the differences between human and mouse could not be established.</p

Fold Promiscuity and Family Counts of Ancient Folds

<p>Ancient SCOP folds were divided into a number of bins according to the number of families that they contain (x-axis). SCOP folds are connected to other “partner” folds in the same protein. The mean promiscuities (the number of unique partner folds a SCOP fold has) of folds in human, mouse and yeast are plotted. As the number of families in a SCOP fold increases, its promiscuity tends to increase. The differences in fold promiscuity between human, mouse, and yeast are larger for folds with larger numbers of families. All promiscuity differences described here between folds with one family and folds with more than one family are significant (MW-test, KS-test: <i>p <</i> 0.02).</p

Detection of collinear blocks by SyntenyMapper.

<p>A: Illustration of a syntenic region between two species, with numbered boxes representing genes and connecting lines representing orthology relationships. Gene and gene have no orthologs in their syntenic regions, but are orthologous to each other. Genes and have no orthologs. B: During pre-processing one-to-many (genes and , ) and asymmetric many-to-many (genes and ), groups are first converted into symmetric groups by excluding genes with the lowest sequence identity to the rest of the group (genes and ), and subsequently paired as one-to-one orthologs based on gene order. Breakpoints (zig-zag lines) are identified as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112341#s2" target="_blank">Methods</a> section. C: Using breakpoints, SyntenyMapper defines rearranged segments, shown in black, as new syntenic regions 1_1 to 1_3 within the long original region.</p

SCOP Hierarchy

<p>Four levels of SCOP are shown: fold, superfamily, family, and sequence (dark blue rectangles). The number of sequences is equal to or greater than the number of families, which is equal to or greater than the number superfamilies, which in turn is equal to or greater than the number of folds.</p

Overview of different approaches for identifying orthologous regions in two genomes.

<p>Sequence-based methods (e.g. ENSEMBL Compara) start with short local alignments that are extended to longest possible alignments over gaps. Breakpoint-based methods use orthologous elements (called ‘anchors') to find the minimum number of rearrangements that transforms one genome into the other. Positional orthology tries to distinguish orthologs from paralogs by analyzing gene neighborhoods.</p

Breakpoint definition in SyntenyMapper.

<p>Illustration of two breakpoints emerging at both ends of a translocated segment in genome <i>A</i> and in genome <i>B</i> (hatched box). By definition a breakpoint is constituted by two orthologous gene pairs and if , as shown in the boxes underneath the schema. The second breakpoint is described by and . White and black boxes mark the four genes forming the first and the second breakpoint, respectively. <i>A</i> is used as reference genome to define the block formed by a micro-rearrangement as the genes that lie between the adjacent breakpoints in <i>A</i>, in this case , and . The genes between these two breakpoints and their orthologs in <i>B</i> form a block.</p

Visualization of SyntenyMapper results for a syntenic region in human and mouse.

<p>The region (ENSEMBL identifier 44542) is illustrated in human as a dark grey ideogram (right) and in mouse as a light grey ideogram (left). Ticks are placed at 100 kB distance and the numbers represent positions in mB on the human and mouse chromosomes 15 and 7, respectively. The Circos circular plot illustrates the positions of genes/intergenic regions for one syntenic region in both species and the correspondence between them. Micro-rearrangements are illustrated by color-coding, with syntenic orthologs and out-of-order genes shown in grey and black, respectively, while the intergenic regions between syntenic orthologs and between out-of-order genes are shown in white. A large block of seven genes (black) was translocated in either human or mouse. In the Galaxy version of the plots, gene annotations are given as labels and as direct links to ENSEMBL through clicks onto the gene track.</p

Frequency of different cases of orthologous relationships for a given gene in a syntenic region between human and mouse.

<p>Italic font indicates classes of genes that are covered by SyntenyMapper. Internal orthologs: Orthologous genes that lie in the same syntenic region. External orthologs: Orthologous genes that lie in different syntenic regions. Syntenic-block-free region: Genomic region that is not covered by ENSEMBL syntenic regions.</p><p>Frequency of different cases of orthologous relationships for a given gene in a syntenic region between human and mouse.</p

Sequence Divergence and Family Counts of Ancient Folds

<p>Ancient SCOP folds found in human proteins were compared to those in mouse and yeast orthologs (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020040#s4" target="_blank">Materials and Methods</a>), and the average divergence was recorded for each fold. The SCOP folds were divided into a number of bins according to the number of families that they contain (<i>x</i>-axis). The mean of the sequence identities in each bin is shown (<i>y</i>-axis) for mouse and yeast. For both organisms, as the number of families in a SCOP fold increases, the sequences that encode the fold become more divergent. Against mouse orthologs, folds with one family were significantly more conserved than those with more than one family (MW-test, Kolmogorov-Smirnov test [KS-test]: <i>p <</i> 0.01). Against yeast orthologs, a significant difference in divergence was observed between folds of one and more than ten families (MW-test, KS-test: <i>p <</i> 0.05).</p

Graphical representation of the isochore assignments for the first 100 Mb of the human chromosome 1 (obtained from the IsoBase web page )

Consensus assignment. The color code depicts the isochore families as defined by Bernardi . [,]Confidence of the assignments. For each residue the number of isochore methods that support a given isochore class is depicted as a red line. Support values for individual bases are averaged over a sliding window (blue line). Isochore predictions made by each of the available methods.<p><b>Copyright information:</b></p><p>Taken from "Assignment of isochores for all completely sequenced vertebrate genomes using a consensus"</p><p>http://genomebiology.com/2008/9/6/R104</p><p>Genome Biology 2008;9(6):R104-R104.</p><p>Published online 30 Jun 2008</p><p>PMCID:PMC2481423.</p><p></p