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Emergence and maintenance of functional modules in signaling pathways.

Soyer OS - BMC Evol. Biol. (2007)

Bottom Line: These evolutionary simulations start with a homogenous population of a minimal pathway containing two effectors coupled to two signals via a single receptor.Such functional modules are maintained as long as mutations leading to new interactions among existing proteins in the pathway are rare.While supporting a neutralistic view for the emergence of modularity in biological systems, these findings highlight the relevant rate of different mutational processes and the distribution of functional pathways in the topology space as key factors for its maintenance.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology (CoSBi), Piazza Manci 17, 38100 Povo (Trento), Italy. soyer@cosbi.eu

ABSTRACT

Background: While detection and analysis of functional modules in biological systems have received great attention in recent years, we still lack a complete understanding of how such modules emerge. One theory is that systems must encounter a varying selection (i.e. environment) in order for modularity to emerge. Here, we provide an alternative and simpler explanation using a realistic model of biological signaling pathways and simulating their evolution.

Results: These evolutionary simulations start with a homogenous population of a minimal pathway containing two effectors coupled to two signals via a single receptor. This population is allowed to evolve under a constant selection pressure for mediating two separate responses. Results of these evolutionary simulations show that under such a selective pressure, mutational processes easily lead to the emergence of pathways with two separate sub-pathways (i.e. modules) each mediating a distinct response only to one of the signals. Such functional modules are maintained as long as mutations leading to new interactions among existing proteins in the pathway are rare.

Conclusion: While supporting a neutralistic view for the emergence of modularity in biological systems, these findings highlight the relevant rate of different mutational processes and the distribution of functional pathways in the topology space as key factors for its maintenance.

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Related in: MedlinePlus

Frequency of different pathway structures during the course of evolution. Different panels show results from sample simulations with increasing probability for protein recruitment (P(rcrtmnt)) in expense of interaction formation (i.e. results from one of the runs used to create Figure 4). Red, blue and black lines show the frequency of modular, crosstalk, and complex pathways (see the legend of Figure 4 for pathway types). Note, that measurements are taken after mutations but before selection, hence there is a small fraction of unconnected pathways at each generation (not shown on the graph).
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Figure 5: Frequency of different pathway structures during the course of evolution. Different panels show results from sample simulations with increasing probability for protein recruitment (P(rcrtmnt)) in expense of interaction formation (i.e. results from one of the runs used to create Figure 4). Red, blue and black lines show the frequency of modular, crosstalk, and complex pathways (see the legend of Figure 4 for pathway types). Note, that measurements are taken after mutations but before selection, hence there is a small fraction of unconnected pathways at each generation (not shown on the graph).

Mentions: Analysis of the distribution of pathway types over the entire evolutionary simulation, we get a clearer picture of the relation between mutational events and modularity. As shown in Figure 5, modular pathways emerge relatively quickly in the population regardless of the relative rate of protein recruitment and interaction formation. However, in presence of the latter process modular pathways are quickly replaced by pathways with crosstalk or complex pathways. Note that while the distribution of modular pathways change in the population, the average fitness remains high (see Additional File 3). Analyzing the effects of different mutational processes on pathway structure, we find that transitions from modular pathways to pathways with crosstalk are extensively caused by interaction addition (data not shown). The reverse transitions, resulting in modular pathways, are solely driven by protein and interaction loss. Hence, the emergence and maintenance of functional modules is mostly determined by the relevant rate of these different mutational processes.


Emergence and maintenance of functional modules in signaling pathways.

Soyer OS - BMC Evol. Biol. (2007)

Frequency of different pathway structures during the course of evolution. Different panels show results from sample simulations with increasing probability for protein recruitment (P(rcrtmnt)) in expense of interaction formation (i.e. results from one of the runs used to create Figure 4). Red, blue and black lines show the frequency of modular, crosstalk, and complex pathways (see the legend of Figure 4 for pathway types). Note, that measurements are taken after mutations but before selection, hence there is a small fraction of unconnected pathways at each generation (not shown on the graph).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2228312&req=5

Figure 5: Frequency of different pathway structures during the course of evolution. Different panels show results from sample simulations with increasing probability for protein recruitment (P(rcrtmnt)) in expense of interaction formation (i.e. results from one of the runs used to create Figure 4). Red, blue and black lines show the frequency of modular, crosstalk, and complex pathways (see the legend of Figure 4 for pathway types). Note, that measurements are taken after mutations but before selection, hence there is a small fraction of unconnected pathways at each generation (not shown on the graph).
Mentions: Analysis of the distribution of pathway types over the entire evolutionary simulation, we get a clearer picture of the relation between mutational events and modularity. As shown in Figure 5, modular pathways emerge relatively quickly in the population regardless of the relative rate of protein recruitment and interaction formation. However, in presence of the latter process modular pathways are quickly replaced by pathways with crosstalk or complex pathways. Note that while the distribution of modular pathways change in the population, the average fitness remains high (see Additional File 3). Analyzing the effects of different mutational processes on pathway structure, we find that transitions from modular pathways to pathways with crosstalk are extensively caused by interaction addition (data not shown). The reverse transitions, resulting in modular pathways, are solely driven by protein and interaction loss. Hence, the emergence and maintenance of functional modules is mostly determined by the relevant rate of these different mutational processes.

Bottom Line: These evolutionary simulations start with a homogenous population of a minimal pathway containing two effectors coupled to two signals via a single receptor.Such functional modules are maintained as long as mutations leading to new interactions among existing proteins in the pathway are rare.While supporting a neutralistic view for the emergence of modularity in biological systems, these findings highlight the relevant rate of different mutational processes and the distribution of functional pathways in the topology space as key factors for its maintenance.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology (CoSBi), Piazza Manci 17, 38100 Povo (Trento), Italy. soyer@cosbi.eu

ABSTRACT

Background: While detection and analysis of functional modules in biological systems have received great attention in recent years, we still lack a complete understanding of how such modules emerge. One theory is that systems must encounter a varying selection (i.e. environment) in order for modularity to emerge. Here, we provide an alternative and simpler explanation using a realistic model of biological signaling pathways and simulating their evolution.

Results: These evolutionary simulations start with a homogenous population of a minimal pathway containing two effectors coupled to two signals via a single receptor. This population is allowed to evolve under a constant selection pressure for mediating two separate responses. Results of these evolutionary simulations show that under such a selective pressure, mutational processes easily lead to the emergence of pathways with two separate sub-pathways (i.e. modules) each mediating a distinct response only to one of the signals. Such functional modules are maintained as long as mutations leading to new interactions among existing proteins in the pathway are rare.

Conclusion: While supporting a neutralistic view for the emergence of modularity in biological systems, these findings highlight the relevant rate of different mutational processes and the distribution of functional pathways in the topology space as key factors for its maintenance.

Show MeSH
Related in: MedlinePlus