SFB 680:  Molecular Basis of Evolutionary Innovations

• Subject Area: Biology ; Medicine
• Term: from 2006 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 13532522

• Final Report Year: 2018

Final Report Abstract

The research of CRC 680 took place amidst rapidly increasing data of genome sequences, gene regulation, and metabolic networks in cells. The new molecular data opened unprecedented opportunities to answer core questions of evolution. We endeavored to understand how differences between species build upon variation within species. By comparative sequence and functional analysis, we showed how functional innovations arise from changes of gene interactions in regulatory and metabolic networks. Repeatable network changes explain, for example, the convergent evolution of photosynthesis, the emergence of new flowering cycles and leaf shapes in plants, and the evolution of embryonal developmental patterns in insects. We also found a complementary mode of innovation: novel genes, which sometimes arise from noncoding genome sequence, can generate lineage-specific biological functions. Of equal importance, CRC 680 developed new, quantitative links between evolutionary experiment, data analysis, and theory. These advances made critical use of time-resolved data from microbial and viral systems, where evolution can be followed in real time. We showed that many such systems have a fast-paced mode of evolution, in which several beneficial mutations compete for success. Which mutations are beneficial is captured by empirical fitness landscapes that we deduced from observed time courses of evolution. But understanding why mutations are beneficial rests on the physical basis of evolution, which was a core theme of the CRC. We studied how mutations affect key biophysical phenotypes in a cell, such as binding affinities, protein stability, and metabolic fluxes, and we quantified how these phenotypes impact organismic functions and fitness. The resulting evolutionary dynamics reveals far-reaching links to statistical physics: equilibrium systems obey a Boltzmann statistics of fitness, while time- dependent fitness drives non-equilibrium adaptive changes. Together, our research lead to a better understanding of fast-evolving systems, including important human pathogens, and paved the way for new applications of evolutionary biology to medicine and public health. More about our research can be found on the CRC 680 website.

Publications

• (2006). A segmentation gene in Tribolium produces a polycistronic mRNA that codes for multiple conserved peptides. Cell 126, 559 - 569
  Savard J., Marques-Souza H., Aranda M., Tautz D.
  (See online at https://doi.org/10.1016/j.cell.2006.05.053)
• (2006). Cross-species analysis of biological networks by Bayesian alignment. Proc. Natl. Acad. Sci. 103:10967-10972
  Berg J., Lässig M.
  (See online at https://doi.org/10.1073/pnas.0602294103)
• (2006). Genomic islands of differentiation between house mouse subspecies. Genome Res 16: 730-737
  Harr B.
  (See online at https://doi.org/10.1101/gr.5045006)
• (2006). The genetics of plant metabolism. Nature Genet. 38: 842-849
  Keurentjes J.J.B., Fu J., de Vos C.H., Lommen A., Hall R.D., Bino R.J., van der Plas L.H., Jansen R.C., Vreugdenhil D., Koornneef M.
  (See online at https://doi.org/10.1146/annurev-genet-120116-024640)
• (2007). Clonal interference in large populations. Proc. Natl. Acad. Sci. 104: 18135-18140
  Park S.C., Krug J.
  (See online at https://doi.org/10.1073/pnas.0705778104)
• (2008). Energy-dependent fitness: a quantitative model for the evolution of yeast transcription factor binding sites. Proc Natl Acad Sci. 105, 12376-81
  Mustonen V., Kinney J., Callan C.G. Jr., Lässig M.
  (See online at https://doi.org/10.1073/pnas.0805909105)
• (2008). Self-regulatory circuits in dorsoventral axis formation of the short-germ beetle Tribolium castaneum. Dev Cell 14, 605-615
  Nunes da Fonseca R., von Levetzow C., Kalscheuer P., Basal A., van der Zee M., Roth S.
  (See online at https://doi.org/10.1016/j.devcel.2008.02.011)
• (2009). Emergence of a new gene from an intergenic region. Curr Biol. 19:1527-31
  Heinen T.J., Staubach F., Häming D., Tautz D.
  (See online at https://doi.org/10.1016/j.cub.2009.07.049)
• (2010). Fitness flux and ubiquity of adaptive evolution, Proc. Natl. Acad. Sci. 107:4248-53
  Mustonen V., Lässig M.
  (See online at https://doi.org/10.1073/pnas.0907953107)
• (2010). Natural variation at Strubbelig Receptor Kinase 3 drives immune-triggered incompatibilities between A. thaliana accessions. Nature Genet. 42:1135-1139
  Alcázar R., García A.V., Kronholm I., de Meaux J., Koornneef M., Parker J.E., Reymond M.
  (See online at https://doi.org/10.1038/ng.704)
• (2010). Phosphorylation of IRG resistance proteins is an evasion strategy for virulent T. gondii strains. PLoS Biology 8: e1000576
  Steinfeldt T., Könen-Waisman S., Tong L., Pawlowski N., Lamkemeyer T., Sibley L.D., Hunn J.P., Howard J.C.
  (See online at https://doi.org/10.1371/journal.pbio.1000576)
• (2011). Evolutionary accessibility of mutational pathways. PLoS Comp. Biol. 7:e1002134
  Franke J., Klözer A., de Visser J.A.G.M., Krug J.
  (See online at https://doi.org/10.1371/journal.pcbi.1002134)
• (2011). Genetic and evolutionary perspectives on the interplay between plant immunity and development. Curr. Opin. Plant Biol. 14:378-384
  Alcázar R., Reymond M., Schmitz G., de Meaux J.
  (See online at https://doi.org/10.1016/j.pbi.2011.04.001)
• (2011). Nonlinear fitness landscape of a molecular pathway. PLoS Genetics 7(7): e1002160
  Perfeito L., Ghozzi S., Berg J., Schnetz K., Lässig M.
  (See online at https://doi.org/10.1371/journal.pgen.1002160)
• (2012). The chromatin insulator CTCF and the emergence of metazoan diversity. Proc. Natl. Acad. Sci. 109:17507
  Heger P., Marin B., Bartkuhn M., Schierenberg E., Wiehe T.
  (See online at https://doi.org/10.1073/pnas.1111941109)
• (2012). The genetic basis of flowering responses to seasonal cues. Nature Reviews Genetics 13:627
  Andrés F., Coupland G.
  (See online at https://doi.org/10.1038/nrg3291)
• (2013). Predictability of evolution depends nonmonotonically on population size. Proc. Natl. Acad. Sci. USA 110:571-576
  Szendro I.G., Franke J., de Visser J.A.G.M., Krug J.
  (See online at https://doi.org/10.1073/pnas.1213613110)
• (2013). Predicting C4 Photosynthesis Evolution: Modular, Individually Adaptive Steps on a Mount Fuji Fitness Landscape. Cell 153:1579-1588
  Heckmann D., Schulze S., Denton A., Gowik U., Westhoff P., Weber A.P.M., Lercher M.J.
  (See online at https://doi.org/10.1016/j.cell.2013.04.058)
• (2013). Symplesiomorphies in the WUSCHEL clade suggest that the last common ancestor of seed plants contained at least four independent stem cell niches. New Phytol. 199:1081-1092
  Nardmann J., Werr W.
  (See online at https://doi.org/10.1111/nph.12343)
• (2013). Toxoplasma gondii and the mouse; reciprocal virulence and resistance polymorphism. eLIFE 10.7554/eLife.01298
  Lilue J., Mueller U.B., Steinfeldt T., Howard J.C.
  (See online at https://doi.org/10.7554/elife.01298)
• (2014). A predictive fitness model for influenza. Nature 507:57-61
  Luksza M., Lässig M.
  (See online at https://doi.org/10.1038/nature13087)
• (2014). Analysis of a plant complex resistance gene locus underlying immune-related hybrid incompatibility and its occurrence in nature. PloS Genet. 10, e1004848
  Alcazar R., von Reth M., Bautor J., Chae E., Weigel D., Koornneef M., Parker J.E.
  (See online at https://doi.org/10.1371/journal.pgen.1004848)
• (2014). Analysis of TTG1 function in Arabis alpina. BMC Plant Biol 14, 16
  Chopra D., Wolff H., Span J., Schellmann S., Coupland G., Albani M.C., Schrader A., Hülskamp M.
  (See online at https://doi.org/10.1186/1471-2229-14-16)
• (2014). Dorsoventral polarity of the Nasonia embryo primarily relies on a BMP gradient formed without input from Toll. Curr Biol 24, 2393-2398
  Özuak O., Buchta T., Roth S., Lynch J.A.
  (See online at https://doi.org/10.1016/j.cub.2014.08.035)
• (2014). Empirical fitness landscapes and the predictability of evolution. Nat. Rev. Genet. 15:480-490
  De Visser J.A.G.M., Krug J.
  (See online at https://doi.org/10.1038/nrg3744)
• (2014). Leaf shape evolution through duplication, regulatory diversification, and loss of a homeobox gene. Science. 343:780-3
  Vlad D., Kierzkowski D., Rast M.I., Vuolo F., Dello Ioio R., Galinha C., Gan X, Hajheidari M., Hay A., Smith R.S., Huijser P., Bailey C.D., Tsiantis M.
  (See online at https://doi.org/10.1126/science.1248384)
• (2014). Natural genetic variation impacts expression levels of coding, non-coding, and antisense transcripts in fission yeast. Mol. Syst. Biol. 10, 764–764
  Clement-Ziza M., …, Beyer A.
  (See online at https://doi.org/10.15252/msb.20145123)
• (2015). Differential interaction forces govern bacterial sorting in early biofilms, eLife, DOI 10.7554/eLife.10811
  Oldewurtel E.R., Kouzel N., Dewenter L., Henseler K., Maier B.
  (See online at https://doi.org/10.7554/elife.10811)
• (2015). Dynamic BMP signalling polarized by Toll patterns the dorsoventral axis in a hemimetabolous insect. Elife 4, e05502
  Sachs L., Chen Y.T., Drechsler A., Lynch J.A., Panfilio K.A., Lässig M., Berg J., Roth S.
  (See online at https://doi.org/10.7554/elife.05502)
• (2018). By land, air, and sea: hemipteran diversity through the genomic lens. Current Opinion in Insect Science 25:106-115
  Panfilio K.A., Angelini D.R.
  (See online at https://doi.org/10.1016/j.cois.2017.12.005)
• (2016) Fitness trade-offs in competence differentiation of Bacillus subtilis, Front. Microbiol. 7, 888
  Yüksel M., Power J.J., Ribbe J., Volkmann T., Maier B.
  (See online at https://doi.org/10.3389/fmicb.2016.00888)
• (2016) On the dependency of cellular protein levels on mRNA abundance. (Review) Cell 165:535-50
  Liu Y., Beyer A., Aebersold R.
  (See online at https://doi.org/10.1016/j.cell.2016.03.014)
• (2016). Adaptive evolution of complex innovations through step-wise metabolic niche expansion. Nature Communications 7:11607
  Szappanos B., Fritzemeier C.J., Csörgő B., Lázár V., Lu X., Fekete G., Bálint B., Herczeg R., Nag I., Notebaart R., Lercher M.J., Pál C., Papp B.
  (See online at https://doi.org/10.1038/ncomms11607)
• (2016). Coupled enhancer and coding sequence evolution of a homeobox gene shaped leaf diversity. Genes Dev. 1;30:2370-2375
  Vuolo F., Mentink R.A., Hajheidari M., Bailey C.D., Filatov D.A., Tsiantis M.
  (See online at https://doi.org/10.1101/gad.290684.116)
• (2016). The impact of Toxoplasma gondii on the mammalian genome. Current Opinion in Microbiology. 32:19-25
  Müller U.B., Howard J.C.
  (See online at https://doi.org/10.1016/j.mib.2016.04.009)
• (2017). Divergence of annual and perennial species in the Brassicaceae and the contribution of cisacting variation at FLC orthologues. Molecular Ecology 26:3437-3457
  Kiefer C., Severing E., Karl R., Bergonzi S., Koch M., Tresch A., Coupland G.
  (See online at https://doi.org/10.1111/mec.14084)
• (2017). Divergence of regulatory networks governed by the orthologous transcription factors FLC and PEP1 in Brassicaceae species. Proc. Natl. Acad. Sci. USA 114:E11037-E11046
  Mateos J.L., Tilmes V., Madrigal P., Severing E., Richter R., Rijkenberg C.W.M., Krajewski P. & Coupland G.
  (See online at https://doi.org/10.1073/pnas.1618075114)
• (2017). Evolution of commensal bacteria in the intestinal tract of mice. Current Opinion in Microbiology 38, 114-121
  Sousa A., Frazão N., Ramiro R.S., Gordo I.
  (See online at https://doi.org/10.1016/j.mib.2017.05.007)
• (2017). Pervasive adaptation of gene expression in Drosophila, Cell Reports 20 (6) 1385-1395
  Nourmohammad A., Rambeau J., Held T., Kovacova V., Berg J., Lässig M.
  (See online at https://doi.org/10.1016/j.celrep.2017.07.033)
• (2017). Predicting evolution. Nature Ecol. Evol. 1:0077
  Lässig M., Mustonen V., Walczak A.
  (See online at https://doi.org/10.1038/s41559-017-0077)