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Research Article

Evolutionary population genetics of promoters: Predicting binding sites and functional phylogenies

Ville Mustonen and Michael Lässig
  1. Institut für Theoretische Physik, Universität zu Köln, Zülpicherstrasse 77, 50937 Cologne, Germany

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PNAS November 1, 2005 102 (44) 15936-15941; https://doi.org/10.1073/pnas.0505537102
Ville Mustonen
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Michael Lässig
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  1. Edited by Tomoko Ohta, National Institute of Genetics, Mishima, Japan (received for review June 30, 2005)

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    Fig. 1.

    Cross-species energy transition probabilities Embedded Image for neutral evolution (blue) and Embedded Image for evolution under time-independent selection in the fitness landscape of Fig. 3a (red). Curves are shown for fixed initial energy E 1 = 8 and various evolutionary distances t. The third curve in each family belongs to the distance between aligned loci of E. coli and S. typhimurium. Typical loci evolve toward weaker binding under neutrality but maintain their binding energy under selection.

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    Fig. 2.

    Functional phylogenies for two species at evolutionary distances t 1 and t 2, counted from their last common ancestor at time ta = 0. Branch segments with neutral evolution are shown in blue with evolution under selection in red. (a) Neutral evolution of nonfunctional loci, described by the energy pair distribution Embedded Image. (b) Evolution of functional loci under time-independent selection, described by the distribution Qt . (c) Evolution under time-dependent selection generating a functional locus in species 1 and a nonfunctional locus in species 2, described by the distribution Embedded Image. This mode involves either a gain of function between ancestor and 1 or a loss of function between ancestor and 2. The switching event at time t′ is denoted by a green arrow. The corresponding mode where the roles of the two species are interchanged is described by the distribution Embedded Image.

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    Fig. 3.

    Energy statistics and fitness landscape for CRP-binding loci in E. coli.(a) Count histogram with energy bins of width 0.1 (black), expected background counts (blue), and excess counts above background (red), with a 30-fold zoom into the region E < 14. The color bar indicates the probability of functionalityρ Q (E), ranging from 1 (red) to 0 (blue). (b) Decomposition of the counts (log-scale, left y axis) according to the single-species hidden Markov model: background distribution (1 - λ)P 0(E) (blue), distribution λQ(E) of functional loci (red), and total distribution W(E) (orange). The resulting fitness landscape ΔF(E) according to Eq. 6 is also shown in orange (thick curve, right y axis).

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    Fig. 4.

    Binding energy pairs and functional histories for aligned loci in E. coli and S. typhimurium.(a) Dot plot of counts (E 1, E 2), including verified binding sites (light blue). The background color shading indicates the likelihood of functional histories, varying between blue (conserved neutrality), red (conserved function), and green (functional switching). Isoprobability lines Embedded Image (α = 0, Q, 0s, s0) are dotted. (b) Energy pair density obtained from the counts (filled contours), compared with the distribution W t (E 1, E 2) (contour lines, W t = 10-7, 10-6, 10-5, 10-4).

Data supplements

  • Mustonen and Lässig et al. 10.1073/pnas.0505537102.

    Supporting Information

    Files in this Data Supplement:

    Supporting Text
    Supporting Figure 5
    Supporting Figure 6
    Supporting Figure 7




    Supporting Figure 5

    Fig. 5. Detection error trade-off for CRP binding site prediction. Expected rates of false positives vs. false negatives for a single-species search with position weight scoring in E. coli (1), a two-species search including S. typhimurium (2), and a three-species search including also Y. pseudotuberculosis (3). The diamonds indicate the points rQ= 0.30, used as lower cutoff in our prediction lists.





    Supporting Figure 6

    Fig. 6. Dot plot of energies for three species comparisons. E1, E2, and E3 refer to E. coli, S. typhimurium, and Y. pseudotuberculosis, respectively.





    Supporting Figure 7

    Fig. 7. Functional phylogenies for three species. Example of the Rt00s(E1,E2,E3) ensemble. Green arrows denote the switching point. Blue lines mark the neutral evolution of nonfunctional loci (Gt0) and red evolution under selection (Gts).

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Evolutionary population genetics of promoters: Predicting binding sites and functional phylogenies
Ville Mustonen, Michael Lässig
Proceedings of the National Academy of Sciences Nov 2005, 102 (44) 15936-15941; DOI: 10.1073/pnas.0505537102

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Evolutionary population genetics of promoters: Predicting binding sites and functional phylogenies
Ville Mustonen, Michael Lässig
Proceedings of the National Academy of Sciences Nov 2005, 102 (44) 15936-15941; DOI: 10.1073/pnas.0505537102
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Proceedings of the National Academy of Sciences of the United States of America: 102 (44)
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