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Constraint and contingency in multifunctional gene regulatory circuits.

Payne JL, Wagner A - PLoS Comput. Biol. (2013)

Bottom Line: Multifunctionality presumably constrains this number, but we do not know to what extent.As a result, historical contingency becomes widespread in circuits with many functions.Circuits with many functions also become increasingly brittle and sensitive to mutation.

View Article: PubMed Central - PubMed

Affiliation: University of Zurich, Institute of Evolutionary Biology and Environmental Studies, Zurich, Switzerland.

ABSTRACT
Gene regulatory circuits drive the development, physiology, and behavior of organisms from bacteria to humans. The phenotypes or functions of such circuits are embodied in the gene expression patterns they form. Regulatory circuits are typically multifunctional, forming distinct gene expression patterns in different embryonic stages, tissues, or physiological states. Any one circuit with a single function can be realized by many different regulatory genotypes. Multifunctionality presumably constrains this number, but we do not know to what extent. We here exhaustively characterize a genotype space harboring millions of model regulatory circuits and all their possible functions. As a circuit's number of functions increases, the number of genotypes with a given number of functions decreases exponentially but can remain very large for a modest number of functions. However, the sets of circuits that can form any one set of functions becomes increasingly fragmented. As a result, historical contingency becomes widespread in circuits with many functions. Whether a circuit can acquire an additional function in the course of its evolution becomes increasingly dependent on the function it already has. Circuits with many functions also become increasingly brittle and sensitive to mutation. These observations are generic properties of a broad class of circuits and independent of any one circuit genotype or phenotype.

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Multifunctional regulatory circuits.Each data point depicts the proportion and number of genotypes with k functions. The data include all k-functions. The line is provided as a visual guide. Note that there are more circuits with  function than with  functions, implying that a randomly selected circuit is more likely to be viable than not. Also note that any circuit with k functions will be included in the count of the number of circuits with between 1 and  functions. The inset shows the number of observed combinations of functions (open circles) and the total number of possible combinations (solid line) of k functions. Note the logarithmic scale of all y-axes.
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pcbi-1003071-g002: Multifunctional regulatory circuits.Each data point depicts the proportion and number of genotypes with k functions. The data include all k-functions. The line is provided as a visual guide. Note that there are more circuits with function than with functions, implying that a randomly selected circuit is more likely to be viable than not. Also note that any circuit with k functions will be included in the count of the number of circuits with between 1 and functions. The inset shows the number of observed combinations of functions (open circles) and the total number of possible combinations (solid line) of k functions. Note the logarithmic scale of all y-axes.

Mentions: We first asked how the number of genotypes that have k functions depends on k. Fig. 2 shows that this number decreases exponentially, implying that multifunctionality constrains the number of viable genotypes severely. For instance, increasing k from 1 to 2 decreases the number of viable genotypes by 34%; further increasing k from 2 to 3 leads to an additional 39% decrease. However, there is always at least one genotype with a given number k of functions, for any . In other words, even in these small circuits, multiple genotypes exist that have many functions.


Constraint and contingency in multifunctional gene regulatory circuits.

Payne JL, Wagner A - PLoS Comput. Biol. (2013)

Multifunctional regulatory circuits.Each data point depicts the proportion and number of genotypes with k functions. The data include all k-functions. The line is provided as a visual guide. Note that there are more circuits with  function than with  functions, implying that a randomly selected circuit is more likely to be viable than not. Also note that any circuit with k functions will be included in the count of the number of circuits with between 1 and  functions. The inset shows the number of observed combinations of functions (open circles) and the total number of possible combinations (solid line) of k functions. Note the logarithmic scale of all y-axes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675121&req=5

pcbi-1003071-g002: Multifunctional regulatory circuits.Each data point depicts the proportion and number of genotypes with k functions. The data include all k-functions. The line is provided as a visual guide. Note that there are more circuits with function than with functions, implying that a randomly selected circuit is more likely to be viable than not. Also note that any circuit with k functions will be included in the count of the number of circuits with between 1 and functions. The inset shows the number of observed combinations of functions (open circles) and the total number of possible combinations (solid line) of k functions. Note the logarithmic scale of all y-axes.
Mentions: We first asked how the number of genotypes that have k functions depends on k. Fig. 2 shows that this number decreases exponentially, implying that multifunctionality constrains the number of viable genotypes severely. For instance, increasing k from 1 to 2 decreases the number of viable genotypes by 34%; further increasing k from 2 to 3 leads to an additional 39% decrease. However, there is always at least one genotype with a given number k of functions, for any . In other words, even in these small circuits, multiple genotypes exist that have many functions.

Bottom Line: Multifunctionality presumably constrains this number, but we do not know to what extent.As a result, historical contingency becomes widespread in circuits with many functions.Circuits with many functions also become increasingly brittle and sensitive to mutation.

View Article: PubMed Central - PubMed

Affiliation: University of Zurich, Institute of Evolutionary Biology and Environmental Studies, Zurich, Switzerland.

ABSTRACT
Gene regulatory circuits drive the development, physiology, and behavior of organisms from bacteria to humans. The phenotypes or functions of such circuits are embodied in the gene expression patterns they form. Regulatory circuits are typically multifunctional, forming distinct gene expression patterns in different embryonic stages, tissues, or physiological states. Any one circuit with a single function can be realized by many different regulatory genotypes. Multifunctionality presumably constrains this number, but we do not know to what extent. We here exhaustively characterize a genotype space harboring millions of model regulatory circuits and all their possible functions. As a circuit's number of functions increases, the number of genotypes with a given number of functions decreases exponentially but can remain very large for a modest number of functions. However, the sets of circuits that can form any one set of functions becomes increasingly fragmented. As a result, historical contingency becomes widespread in circuits with many functions. Whether a circuit can acquire an additional function in the course of its evolution becomes increasingly dependent on the function it already has. Circuits with many functions also become increasingly brittle and sensitive to mutation. These observations are generic properties of a broad class of circuits and independent of any one circuit genotype or phenotype.

Show MeSH
Related in: MedlinePlus