Kinetics effects of WGD and deletions.

<p>A) Outline of a minimal mitotic cell cycle model <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008201#pone.0008201-Goldbeter1" target="_blank">[29]</a>, based on a cascade of post-translational modifications that modulates in the end a protease degrading a cyclin. Such a negative feedback loop generates oscillations. B) The blue curve is the periodic variation of cyclin with the set of parameters of Goldbeter (1991). The green curve (with faster cycling) corresponds to parameters for doubled enzyme concentrations resulting from a WGD followed by extensive DNA deletions.</p

Non-specific protein-DNA interactions and WGD.

<p>A) Original diploid cell. Blue lines: chromosomes, green segments on the chromosomes: TF-encoding gene, yellow chromosomal segments: specific TF target binding sites, green triangles: TF protein. B) Cell after WGD. The cell volume has doubled and the concentrations of bound sites in the tetraploid (specifically or non-specifically) are the same as in the original cell. C) Cell after WGD+DNA deletions. Duplicated ‘superfluous’ DNA is removed leading to a volume shrinkage. This leads to doubling the concentration of TF-sDNA (specific interactions) with respect to the original autopolyploid or tetraploid. D) WGD+generation of junk/selfish DNA that replaces deleted DNA (red lines). Duplicated chromosomes are differentiated (diploidization) and cell volume is similar to that of the original tetraploid and the concentrations TF-sDNA and TF-nsDNA are respected.</p

Dynamics of the formation of the dimer MM (in balance with monomer N) and genome duplication.

<p>Formation of MM depends on the synthesis rate S, the degradation of the coding mRNA and monomers (D) and the interaction of the monomers. Blue curve: dimer formation after WGD (parameters S = D = 1) and red curve dimerization after WGD+deletions (leaving only M, N and the protease-encoding genes as duplicates, S = D = 2). Notice that the steady state is reached more rapidly in the latter system (red curve) than in the orginal tetraploid or diploid (blue curve). Such a kinetic difference can be crucial, especially especially if time delays (as in the mitotic clock of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008201#pone-0008201-g003" target="_blank">figure 3</a>) are important. If MM is in balance with monomers N, there might be a problem before reaching the steady state.</p

The triple cost of polyploidy.

<p>A) Original diploid cell. Chromosomes are represented as blue lines. B) Cell after whole genome duplication (WGD). Notice that the cellular volume has doubled. C) After WGD superfluous gene copies can become junk DNA or be replaced by selfish DNA. This avoids paying the cost of transcription and translation of vast genomic regions and contributes to the rediploidization process.</p

Quantitative exploration of specific transcription factor binding in the presence of different levels of non specific binding.

<p>Quantitative exploration of specific transcription factor binding in the presence of different levels of non specific binding. Consider a TF ([TF] = 1 nM) that specifically recognizes 10 binding sites/nucleus. Specific recognition takes place with Ks' ranging between 10⁸ to 10¹⁴) while non-specific recognition takes place with much lower affinity. Intranuclear concentration of specific target sites is about 3.10⁻¹¹M (assuming a nuclear volume of 5.10⁻¹³L). The initial concentration of irrelevant DNA binding sites is assumed to be 7 orders of magnitude higher than sDNA. The color scale represents the ratio of the concentration of TF bound to specific site on DNA in the case WGD+ (leaving TF and its targets duplicated) over the concentration of TF bound to specific sites before WGD. For low non-specific binding the concentration of specifically bound TF targets in WGD+ is twice as much as in the case without WGD (blue zone). In presence of significant non-specific binding, the concentration of specifically bound sites can be as much as 4× higher than without duplication as the synthesis of TFs is doubled whereas non-specific binding sites available for sequestration are in identical concentration. The example of TF1 and TF2 (in balance) is displayed. TF1 and TF2 have the same global concentration but TF1 binds only specifically and TF2 has substantial non-specific binding. Under the scenario WGD+, TF2 might form as much as two times more complexes than TF1, which obviously would perturb their balance.</p

Functional clustering of genes whose expression profiles stronlgy correlate with those of dLBR and CG1998 (using the DAVID classification tool at Medium stringency).

<p>ER: endoplasmic reticulum, HSP: heat shock protein, SRP: signal recognition particle. At high stringency, only the first functional cluster is obtained.</p

Hydrophobic profiles of several potential ERG orthologous proteins.

<p>A way to show a structural relationship is to predict the hydrophobic profiles of the relevant proteins. Here we have used the TopPred program <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002883#pone.0002883-Claros1" target="_blank">[36]</a> as implemented in the server of Pasteur Institute (<a href="http://www.pasteur.fr" target="_blank">http://www.pasteur.fr</a>). Left panels show the results for the potential homologs of ERG2p while the right panels display the profiles for ERG28p homologs (using the Kyte-Doolitle scale, with the default parameters). Negative (positive) values represent hydrophobic (hydrophilic) segments. A way to statistically assess the similarity of two profiles is to calculate their correlation coefficient R. R-values for pairwise comparisons with the human sequence are reported. We tried to maximize the R-value by slightly sliding one profile over the other (that is why the frames of the profiles are not perfectly aligned).</p

Segments of the <i>Drosophila</i> paralogs CG1998 and CG11162 (homologs of Erg25) and the corresponding conceptual translations.

<p>The interruption of the open reading frames of both genes, by their last intron, is shown by vertical lines.</p

Outline of the ergosterol synthesis pathway in yeast.

<p>(+) the corresponding gene is present in <i>C. elegans</i> and <i>D. melanogaster</i>, according to our exploration. (−) the corresponding gene is absent. (?) not convincing evidence for the presence of the ortholog.</p

Expressional correlation among <i>D. melanogaster ERG</i> orthologs.

<p>The analyses were performed using data downloaded from the Gene expression-Omnibus database (<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgiCMDsearchDBgeo" target="_blank">http://www.ncbi.nlm.nih.gov/entrez/query.fcgiCMDsearchDBgeo</a>). We considered the datasets GDS192 (wing imaginal disc spatial gene expression), GDS653 (neurotransmitter-specific neuronal gene expression), GDS664 (splicing factor mutant at permissive and restrictive temperatures) and GDS667 (mRNA splicing factor knock-down) which contain 51 data points for 14 000 transcripts.</p