Results of reductive evolution simulations under nutrient-limited and nutrient-rich conditions.

<p>Results of reductive evolution simulations under nutrient-limited and nutrient-rich conditions.</p

Network reconstruction protocol.

<p>Schematic representation of the reconstruction of ancestral and extant genome-scale metabolic networks of <i>S. glossinidius</i>. For a detailed explanation of the protocol, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030652#pone.0030652.s009" target="_blank">Methods S1</a>.</p

Comparison of the genome characteristics and <i>in silico</i> metabolic networks of <i>S. glossinidius</i>, <i>B. aphidicola</i> APS and <i>E. coli</i> K12.

<p>Comparison of the genome characteristics and <i>in silico</i> metabolic networks of <i>S. glossinidius</i>, <i>B. aphidicola</i> APS and <i>E. coli</i> K12.</p

Robustness analysis on <i>E. coli</i> K12, <i>S. glossinidius</i> and <i>B. aphidicola</i> BAp and <i>B. aphidicola</i> BCc metabolic networks.

<p>The fraction of essential and non-essential genes in single knockout simulations on different genome-scale metabolic networks is represented. Essential genes are defined as those genes whose deletion results in a decrease of more than 99% of the original biomass production.</p

Phosphoenolpyruvate carboxylase (PPC reaction) inactivation effect in <i>E. coli</i> K12 iJR904 and <i>S. glossinidius</i> metabolic networks.

<p>Reactions of glycolysis, TCA cycle, and transport and metabolization of external L-arginine are represented together with their corresponding reaction fluxes in FBA simulations. Red metabolites are included in the biomass equation. Black values correspond to reaction fluxes in the <i>E. coli</i> K12 iJR904 network with glucose as sole external carbon source. Red values correspond to reaction fluxes in the <i>E. coli</i> K12 iJR904 network under the same conditions but removing the PPC reaction. Green values correspond to reaction fluxes in the <i>S. glossinidius</i> ancestral network, with glucose as sole external carbon source. Purple values correspond to reaction fluxes in the <i>S. glossinidius</i> extant network with glucose and L-arginine as external metabolites. Reaction fluxes are represented in mmol gr DryWeight⁻¹ hr⁻¹.</p

Results of the construction and manual curation of the metamodel.

<p>Results of the construction and manual curation of the metamodel.</p

Workflow diagram of the gap-filling process.

<p>The set of blocked is classified either as non-metablocked or Metablocked. Metablocked (red) reactions are the ones that couldn't be curated on the metamodel and thus are excluded or removed from the models. Non-metablockeds, are reactions found blocked in at least one GSM but actives in the metamodel and thus can be curated in the GSM. gap-filling reactions (green) are the set of reactions that need to be added to a model in order to unblocked the complete set of blocked non-metablocked. Finally, some of the gap-filling reactions can be associated to one or more genes (mapped) whereas others remain orphans.</p

Three examples of pathways unblocked as a consequences of the metamodel construction.

<p>In a) a partial representation of the aerobic degradation of catechol is depicted (metabolites in circles were manually added to clarify the diagram). In b) the import of choline sulfate is shown as an example of an in-to-out linear pathway artifact. In c) an example of an artifact is shown, with a set of reactions corresponding to two different variants of the adenosylcobalamin biosynthetic pathway: early cobalt insertion (right side); late cobalt incorporation (left side). Cofactors and currency metabolites were excluded from this representation. Metabolite abbreviations can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143626#pone.0143626.s008" target="_blank">S3C Table</a>.</p

Relation between the pathways: methanogeneis from CO2 and the so-called formaldehyde oxidation V (H4MPT).

<p>Black colored reactions were removed from metamodel because they belong exclusively to the methanogenic pathway. The white colored reaction is involved in the metanogenesis but also in the formaldehyde oxidation V (H4MPT) pathway. Grey reactions belonging to the formaldehyde oxidation V (H4MPT) pathway and were manually added to the metamodel to gap-fill the former pathway. Metabolite abbreviations can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143626#pone.0143626.s008" target="_blank">S3C Table</a>.</p

Consistency analysis of 130 GSMs.

<p>a) the number of blocked reactions found in each GSM is plotted against the number of total reactions. Grey lines represent iso-probabilities (20%, 25%, and so). Colors of dots correspond to the groups of the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143626#pone.0143626.g002" target="_blank">Fig 2A</a> previously published [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143626#pone.0143626.ref037" target="_blank">37</a>], and are also included in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143626#pone.0143626.s006" target="_blank">S1A Table</a>; b) the times a reaction was found in a GSM is plotted against the times it was found blocked. The main diagonal indicates reactions found blocked in all the GSMs where they were present.</p