Low protein expression enhances phenotypic evolvability by intensifying selection on folding stability.


Journal

Nature ecology & evolution
ISSN: 2397-334X
Titre abrégé: Nat Ecol Evol
Pays: England
ID NLM: 101698577

Informations de publication

Date de publication:
08 2022
Historique:
received: 17 12 2021
accepted: 19 05 2022
pubmed: 8 7 2022
medline: 6 8 2022
entrez: 7 7 2022
Statut: ppublish

Résumé

Protein abundance affects the evolution of protein genotypes, but we do not know how it affects the evolution of protein phenotypes. Here we investigate the role of protein abundance in the evolvability of green fluorescent protein (GFP) towards the novel phenotype of cyan fluorescence. We evolve GFP in E. coli through multiple cycles of mutation and selection and show that low GFP expression facilitates the evolution of cyan fluorescence. A computational model whose predictions we test experimentally helps explain why: lowly expressed proteins are under stronger selection for proper folding, which facilitates their evolvability on short evolutionary time scales. The reason is that high fluorescence can be achieved by either few proteins that fold well or by many proteins that fold less well. In other words, we observe a synergy between a protein's scarcity and its stability. Because many proteins meet the essential requirements for this scarcity-stability synergy, it may be a widespread mechanism by which low expression helps proteins evolve new phenotypes and functions.

Identifiants

pubmed: 35798838
doi: 10.1038/s41559-022-01797-w
pii: 10.1038/s41559-022-01797-w
pmc: PMC7613228
mid: EMS145180
doi:

Substances chimiques

Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1155-1164

Subventions

Organisme : Swiss National Science Foundation
ID : 172887
Pays : Switzerland

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Newman, J. R. et al. Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature 441, 840–846 (2006).
pubmed: 16699522 doi: 10.1038/nature04785
Silander, O. K. et al. A genome-wide analysis of promoter-mediated phenotypic noise in Escherichia coli. PLoS Genet. 8, e1002443 (2012).
pubmed: 22275871 pmcid: 3261926 doi: 10.1371/journal.pgen.1002443
Lehner, B. Selection to minimise noise in living systems and its implications for the evolution of gene expression. Mol. Syst. Biol. 4, 170 (2008).
pubmed: 18319722 pmcid: 2290932 doi: 10.1038/msb.2008.11
Pál, C., Papp, B. & Lercher, M. J. An integrated view of protein evolution. Nat. Rev. Genet. 7, 337–348 (2006).
pubmed: 16619049 doi: 10.1038/nrg1838
Bershtein, S., Goldin, K. & Tawfik, D. S. Intense neutral drifts yield robust and evolvable consensus proteins. J. Mol. Biol. 379, 1029–1044 (2008).
pubmed: 18495157 doi: 10.1016/j.jmb.2008.04.024
Socha, R. D., Chen, J. & Tokuriki, N. The molecular mechanisms underlying hidden phenotypic variation among metallo-β-lactamases. J. Mol. Biol. 431, 1172–1185 (2019).
pubmed: 30769117 doi: 10.1016/j.jmb.2019.01.041
Dasmeh, P. & Serohijos, A. W. Estimating the contribution of folding stability to nonspecific epistasis in protein evolution. Proteins 86, 1242–1250 (2018).
pubmed: 30039542 doi: 10.1002/prot.25588
Bershtein, S. et al. Protein homeostasis imposes a barrier on functional integration of horizontally transferred genes in bacteria. PLoS Genet. 11, e1005612 (2015).
pubmed: 26484862 pmcid: 4618355 doi: 10.1371/journal.pgen.1005612
Laurent, J. M. et al. Protein abundances are more conserved than mRNA abundances across diverse taxa. Proteomics 10, 4209–4212 (2010).
pubmed: 21089048 pmcid: 3113407 doi: 10.1002/pmic.201000327
Zhang, J. & Yang, J.-R. Determinants of the rate of protein sequence evolution. Nat. Rev. Genet. 16, 409–420 (2015).
pubmed: 26055156 pmcid: 4523088 doi: 10.1038/nrg3950
Stefani, M. & Dobson, C. M. Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. 81, 678–699 (2003).
pubmed: 12942175 doi: 10.1007/s00109-003-0464-5
Yang, J. R., Zhuang, S. M. & Zhang, J. Impact of translational error‐induced and error‐free misfolding on the rate of protein evolution. Mol. Syst. Biol. 6, 421 (2010).
pubmed: 20959819 pmcid: 2990641 doi: 10.1038/msb.2010.78
Moutinho, A. F., Trancoso, F. F. & Dutheil, J. Y. The impact of protein architecture on adaptive evolution. Mol. Biol. Evol. 36, 2013–2028 (2019).
pubmed: 31147689 pmcid: 6735723 doi: 10.1093/molbev/msz134
Moutinho, A. F., Bataillon, T. & Dutheil, J. Y. Variation of the adaptive substitution rate between species and within genomes. Evol. Ecol. 34, 315–338 (2020).
doi: 10.1007/s10682-019-10026-z
Yip, S. H.-C. & Matsumura, I. Substrate ambiguous enzymes within the Escherichia coli proteome offer different evolutionary solutions to the same problem. Mol. Biol. Evol. 30, 2001–2012 (2013).
pubmed: 23728795 pmcid: 3842161 doi: 10.1093/molbev/mst105
Larion, M., Moore, L. B., Thompson, S. M. & Miller, B. G. Divergent evolution of function in the ROK sugar kinase superfamily: role of enzyme loops in substrate specificity. Biochemistry 46, 13564–13572 (2007).
pubmed: 17979299 doi: 10.1021/bi700924d
Serohijos, A. W., Rimas, Z. & Shakhnovich, E. I. Protein biophysics explains why highly abundant proteins evolve slowly. Cell Rep. 2, 249–256 (2012).
pubmed: 22938865 pmcid: 3533372 doi: 10.1016/j.celrep.2012.06.022
Leuenberger, P. et al. Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability. Science 355, eaai7825 (2017).
pubmed: 28232526 doi: 10.1126/science.aai7825
Serohijos, A. W., Lee, S. R. & Shakhnovich, E. I. Highly abundant proteins favor more stable 3D structures in yeast. Biophys. J. 104, L1–L3 (2013).
pubmed: 23442924 pmcid: 3566449 doi: 10.1016/j.bpj.2012.11.3838
Bloom, J. D., Labthavikul, S. T., Otey, C. R. & Arnold, F. H. Protein stability promotes evolvability. Proc. Natl. Acad. Sci. USA 103, 5869–5874 (2006).
pubmed: 16581913 pmcid: 1458665 doi: 10.1073/pnas.0510098103
Zheng, J., Guo, N. & Wagner, A. Selection enhances protein evolvability by increasing mutational robustness and foldability. Science 370, eabb5962 (2020).
pubmed: 33273072 doi: 10.1126/science.abb5962
Tokuriki, N., Stricher, F., Serrano, L. & Tawfik, D. S. How protein stability and new functions trade off. PLoS Comput. Biol. 4, e1000002 (2008).
pubmed: 18463696 pmcid: 2265470 doi: 10.1371/journal.pcbi.1000002
Keseler, I. M. et al. The EcoCyc database: reflecting new knowledge about Escherichia coli K-12. Nucleic Acids Res. 45, D543–D550 (2017).
pubmed: 27899573 doi: 10.1093/nar/gkw1003
Zaslaver, A. et al. A comprehensive library of fluorescent transcriptional reporters for Escherichia coli. Nat. Methods 3, 623–628 (2006).
pubmed: 16862137 doi: 10.1038/nmeth895
Wu, Z. et al. Expression level is a major modifier of the fitness landscape of a protein coding gene. Nat. Ecol. Evol. 6, 103–115 (2022).
pubmed: 34795386 doi: 10.1038/s41559-021-01578-x
Pakula, A. A. & Sauer, R. T. Genetic analysis of protein stability and function. Annu. Rev. Genet. 23, 289–310 (1989).
pubmed: 2694933 doi: 10.1146/annurev.ge.23.120189.001445
Sarkisyan, K. S. et al. Local fitness landscape of the green fluorescent protein. Nature 533, 397–401 (2016).
pubmed: 27193686 pmcid: 4968632 doi: 10.1038/nature17995
Mitchell, R. L. Permanence of the log-normal distribution. J. Opt. Soc. Am. 58, 1267–1272 (1968).
doi: 10.1364/JOSA.58.001267
Tokuriki, N. & Tawfik, D. S. Stability effects of mutations and protein evolvability. Curr. Opin. Struct. Biol. 19, 596–604 (2009).
pubmed: 19765975 doi: 10.1016/j.sbi.2009.08.003
Zheng, J., Payne, J. L. & Wagner, A. Cryptic genetic variation accelerates evolution by opening access to diverse adaptive peaks. Science 365, 347–353 (2019).
pubmed: 31346060 doi: 10.1126/science.aax1837
Crameri, A., Whitehorn, E. A., Tate, E. & Stemmer, W. P. Improved green fluorescent protein by molecular evolution using DNA shuffling. Nat. Biotechnol. 14, 315–319 (1996).
pubmed: 9630892 doi: 10.1038/nbt0396-315
Fukuda, H., Arai, M. & Kuwajima, K. Folding of green fluorescent protein and the cycle3 mutant. Biochemistry 39, 12025–12032 (2000).
pubmed: 11009617 doi: 10.1021/bi000543l
Nam, S. H., Oh, K. H., Kim, G. J. & Kim, H. S. Functional tuning of a salvaged green fluorescent protein variant with a new sequence space by directed evolution. Protein Eng. 16, 1099–1105 (2003).
pubmed: 14983092 doi: 10.1093/protein/gzg146
Heim, R. & Tsien, R. Y. Engineering green fluorescent protein for improved brightness, longer wavelengths and fluorescence resonance energy transfer. Curr. Biol. 6, 178–182 (1996).
pubmed: 8673464 doi: 10.1016/S0960-9822(02)00450-5
Drummond, D. A., Raval, A. & Wilke, C. O. A single determinant dominates the rate of yeast protein evolution. Mol. Biol. Evol. 23, 327–337 (2006).
pubmed: 16237209 doi: 10.1093/molbev/msj038
Plotkin, J. B. & Fraser, H. B. Assessing the determinants of evolutionary rates in the presence of noise. Mol. Biol. Evol. 24, 1113–1121 (2007).
pubmed: 17347158 doi: 10.1093/molbev/msm044
Maddamsetti, R. Universal constraints on protein evolution in the long-term evolution experiment with Escherichia coli. Genome Biol. Evol. https://doi.org/10.1093/gbe/evab070 (2021).
LaBar, T. & Adami, C. Evolution of drift robustness in small populations. Nat. Commun. 8, 1012 (2017).
pubmed: 29044114 pmcid: 5647343 doi: 10.1038/s41467-017-01003-7
Raser, J. M. & O’shea, E. K. Noise in gene expression: origins, consequences, and control. Science 309, 2010–2013 (2005).
pubmed: 16179466 pmcid: 1360161 doi: 10.1126/science.1105891
Hardin, J. & Wilson, J. A note on oligonucleotide expression values not being normally distributed. Biostatistics 10, 446–450 (2009).
pubmed: 19276243 doi: 10.1093/biostatistics/kxp003
Ham, L., Brackston, R. D. & Stumpf, M. P. Extrinsic noise and heavy-tailed laws in gene expression. Phys. Rev. Lett. 124, 108101 (2020).
pubmed: 32216388 doi: 10.1103/PhysRevLett.124.108101
Furusawa, C., Suzuki, T., Kashiwagi, A., Yomo, T. & Kaneko, K. Ubiquity of log-normal distributions in intra-cellular reaction dynamics. Biophysics 1, 25–31 (2005).
pubmed: 27857550 pmcid: 5036630 doi: 10.2142/biophysics.1.25
Casellas, J. & Varona, L. Modeling skewness in human transcriptomes. PLoS ONE 7, e38919 (2012).
pubmed: 22701729 pmcid: 3372486 doi: 10.1371/journal.pone.0038919
Bengtsson, M., Ståhlberg, A., Rorsman, P. & Kubista, M. Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels. Genome Res. 15, 1388–1392 (2005).
pubmed: 16204192 pmcid: 1240081 doi: 10.1101/gr.3820805
Bódi, Z. et al. Phenotypic heterogeneity promotes adaptive evolution. PLoS Biol. 15, e2000644 (2017).
pubmed: 28486496 pmcid: 5423553 doi: 10.1371/journal.pbio.2000644
Zhang, Z., Qian, W. & Zhang, J. Positive selection for elevated gene expression noise in yeast. Mol. Syst. Biol. 5, 299 (2009).
pubmed: 19690568 pmcid: 2736655 doi: 10.1038/msb.2009.58
Acar, M., Mettetal, J. T., & Van Oudenaarden, A. Stochastic switching as a survival strategy in fluctuating environments. Nat. Genet. 40, 471–475 (2008).
pubmed: 18362885 doi: 10.1038/ng.110
Kacser, H., Burns, J. A., Kacser, H. & Fell, D. The control of flux. Biochem. Soc. Trans. 23, 341–366 (1995).
pubmed: 7672373 doi: 10.1042/bst0230341
Chen, P. & Shakhnovich, E. I. Lethal mutagenesis in viruses and bacteria. Genetics 183, 639–650 (2009).
pubmed: 19620390 pmcid: 2766323 doi: 10.1534/genetics.109.106492
Soskine, M. & Tawfik, D. S. Mutational effects and the evolution of new protein functions. Nat. Rev. Genet. 11, 572–582 (2010).
pubmed: 20634811 doi: 10.1038/nrg2808
Hoekstra, H. E. et al. Strength and tempo of directional selection in the wild. Proc. Natl. Acad. Sci. USA 98, 9157–9160 (2001).
pubmed: 11470913 pmcid: 55389 doi: 10.1073/pnas.161281098
Oz, T. et al. Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution. Mol. Biol. Evol. 31, 2387–2401 (2014).
pubmed: 24962091 pmcid: 4137714 doi: 10.1093/molbev/msu191
Jahn, L. J., Munck, C., Ellabaan, M. M. H. & Sommer, M. O. A. Adaptive laboratory evolution of antibiotic resistance using different selection regimes lead to similar phenotypes and genotypes. Front. Microbiol. 8, 816–816 (2017).
pubmed: 28553265 pmcid: 5425606 doi: 10.3389/fmicb.2017.00816
Zimmer, M. Green fluorescent protein (GFP): applications, structure, and related photophysical behavior. Chem. Rev. 102, 759–782 (2002).
pubmed: 11890756 doi: 10.1021/cr010142r
Cormack, B. P., Valdivia, R. H. & Falkow, S. FACS-optimized mutants of the green fluorescent protein (GFP). Gene 173, 33–38 (1996).
pubmed: 8707053 doi: 10.1016/0378-1119(95)00685-0
Warren, D. J. Preparation of highly efficient electrocompetent Escherichia coli using glycerol/mannitol density step centrifugation. Anal. Biochem. 413, 206–207 (2011).
pubmed: 21362398 doi: 10.1016/j.ab.2011.02.036
Khersonsky, O. & Tawfik, D. S. Enzyme promiscuity: a mechanistic and evolutionary perspective. Annu. Rev. Biochem. 79, 471–505 (2010).
pubmed: 20235827 doi: 10.1146/annurev-biochem-030409-143718
Aharoni, A. et al. The ‘evolvability’ of promiscuous protein functions. Nat. Genet. 37, 73–76 (2005).
pubmed: 15568024 doi: 10.1038/ng1482
Rhoads, A. & Au, K. F. PacBio sequencing and its applications. Genom. Proteom. Bioinform. 13, 278–289 (2015).
doi: 10.1016/j.gpb.2015.08.002
Chaisson, M. J. & Tesler, G. Mapping single molecule sequencing reads using basic local alignment with successive refinement (BLASR): application and theory. BMC Bioinform. 13, 238 (2012).
doi: 10.1186/1471-2105-13-238
Li, H. et al. The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
pubmed: 19505943 pmcid: 2723002 doi: 10.1093/bioinformatics/btp352
Kumar, S., Stecher, G., Li, M., Knyaz, C. & Tamura, K. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol. Biol. Evol. 35, 1547 (2018).
pubmed: 29722887 pmcid: 5967553 doi: 10.1093/molbev/msy096

Auteurs

Shraddha Karve (S)

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland.
Ashoka University, Sonipat, India.

Pouria Dasmeh (P)

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland.
Swiss Institute of Bioinformatics, Quartier Sorge-Batiment Genopode, Lausanne, Switzerland.

Jia Zheng (J)

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland.
Swiss Institute of Bioinformatics, Quartier Sorge-Batiment Genopode, Lausanne, Switzerland.

Andreas Wagner (A)

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland. andreas.wagner@ieu.uzh.ch.
Swiss Institute of Bioinformatics, Quartier Sorge-Batiment Genopode, Lausanne, Switzerland. andreas.wagner@ieu.uzh.ch.
The Santa Fe Institute, Santa Fe, NM, USA. andreas.wagner@ieu.uzh.ch.
Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa. andreas.wagner@ieu.uzh.ch.

Articles similaires

T-Lymphocytes, Regulatory Lung Neoplasms Proto-Oncogene Proteins p21(ras) Animals Humans

Pathogenic mitochondrial DNA mutations inhibit melanoma metastasis.

Spencer D Shelton, Sara House, Luiza Martins Nascentes Melo et al.
1.00
DNA, Mitochondrial Humans Melanoma Mutation Neoplasm Metastasis
Databases, Protein Protein Domains Protein Folding Proteins Deep Learning
Populus Soil Microbiology Soil Microbiota Fungi

Classifications MeSH