1 Evolvability of Chaperonin Substrate Proteins

Molecular chaperones ensure that their substrate proteins reach the functional native state, and prevent their aggregation. Recently, an additional function was proposed for molecular chaperones: they serve as buffers (capacitors) for evolution by permitting their substrate proteins to mutate and at the same time still allowing them to fold productively. Using pairwise alignments of E. coli genes with genes from other gamma-proteobacteria, we showed that the described buffering effect cannot be observed among substrate proteins of GroEL, an essential chaperone in E. coli. Instead, we find that GroEL substrate proteins evolve less than other soluble E. coli proteins. We analyzed several specific structural and biophysical properties of proteins to assess their influence on protein evolution and to find out why specifically GroEL substrates do not show the expected higher divergence from their orthologs. Our results culminate in four main findings: 1. We find little evidence that GroEL in E.coli acts as a capacitor for evolution in vivo. 2. GroEL substrates evolved less than other E. coli proteins. 3. Predominantly structural features appear to be a strong determinant of evolutionary rate. 4. Besides size, hydrophobicity is a criterion for exclusion for a protein as a chaperonin substrate. N at ur e P re ce di ng s : h dl :1 01 01 /n pr e. 20 09 .2 96 8. 1 : P os te d 23 M ar 2 00 9

[1]  Claus O. Wilke,et al.  Mistranslation-Induced Protein Misfolding as a Dominant Constraint on Coding-Sequence Evolution , 2008, Cell.

[2]  Tong Zhou,et al.  Contact Density Affects Protein Evolutionary Rate from Bacteria to Animals , 2008, Journal of Molecular Evolution.

[3]  Alex Wong,et al.  Evolution of protein-coding genes in Drosophila. , 2008, Trends in genetics : TIG.

[4]  D. Frishman,et al.  Protein abundance profiling of the Escherichia coli cytosol , 2008, BMC Genomics.

[5]  R. Korona,et al.  Molecular chaperones and selection against mutations , 2008, Biology Direct.

[6]  Tim J. P. Hubbard,et al.  Data growth and its impact on the SCOP database: new developments , 2007, Nucleic Acids Res..

[7]  Melanie A. Huntley,et al.  Evolution of genes and genomes on the Drosophila phylogeny , 2007, Nature.

[8]  J. Kato,et al.  Construction of consecutive deletions of the Escherichia coli chromosome , 2007, Molecular systems biology.

[9]  Ziheng Yang.  PAML 4: phylogenetic analysis by maximum likelihood. , 2007, Molecular biology and evolution.

[10]  P. Yeyati,et al.  Hsp90 Selectively Modulates Phenotype in Vertebrate Development , 2007, PLoS genetics.

[11]  Billie J. Swalla,et al.  The Hsp90 Capacitor, Developmental Remodeling, and Evolution: The Robustness of Gene Networks and the Curious Evolvability of Metamorphosis , 2007, Critical reviews in biochemistry and molecular biology.

[12]  Dennis B. Troup,et al.  NCBI GEO: mining tens of millions of expression profiles—database and tools update , 2006, Nucleic Acids Res..

[13]  Ben-Yang Liao,et al.  Impacts of gene essentiality, expression pattern, and gene compactness on the evolutionary rate of mammalian proteins. , 2006, Molecular biology and evolution.

[14]  Frances H Arnold,et al.  Structural determinants of the rate of protein evolution in yeast. , 2006, Molecular biology and evolution.

[15]  C. Wilke,et al.  A single determinant dominates the rate of yeast protein evolution. , 2006, Molecular biology and evolution.

[16]  D. J. Naylor,et al.  Proteome-wide Analysis of Chaperonin-Dependent Protein Folding in Escherichia coli , 2005, Cell.

[17]  C. Wilke,et al.  Why highly expressed proteins evolve slowly. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. E. Hirsh,et al.  Functional genomic analysis of the rates of protein evolution. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Jianzhi Zhang,et al.  Significant impact of protein dispensability on the instantaneous rate of protein evolution. , 2005, Molecular biology and evolution.

[20]  L. Serrano,et al.  Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins , 2004, Nature Biotechnology.

[21]  Robert C. Edgar,et al.  MUSCLE: a multiple sequence alignment method with reduced time and space complexity , 2004, BMC Bioinformatics.

[22]  Susan Lindquist,et al.  Under cover: causes, effects and implications of Hsp90‐mediated genetic capacitance , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[23]  Michael I. Jordan,et al.  Toward a protein profile of Escherichia coli: Comparison to its transcription profile , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Lennart Martens,et al.  Chromatographic Isolation of Methionine-containing Peptides for Gel-free Proteome Analysis , 2002, Molecular & Cellular Proteomics.

[25]  Santiago F. Elena,et al.  Endosymbiotic bacteria: GroEL buffers against deleterious mutations , 2002, Nature.

[26]  S. Lindquist,et al.  Hsp90 as a capacitor of phenotypic variation , 2002, Nature.

[27]  F. Hartl,et al.  Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein , 2002, Science.

[28]  Claudia Neuhauser,et al.  The pattern of amino acid replacements in alpha/beta-barrels. , 2002, Molecular biology and evolution.

[29]  Jason C. Young,et al.  Hsp90: a specialized but essential protein-folding tool. , 2001, The Journal of cell biology.

[30]  A. E. Hirsh,et al.  Protein dispensability and rate of evolution , 2001, Nature.

[31]  C. Pál,et al.  Highly expressed genes in yeast evolve slowly. , 2001, Genetics.

[32]  R. Wierenga,et al.  The TIM‐barrel fold: a versatile framework for efficient enzymes , 2001, FEBS letters.

[33]  P. Bork,et al.  Homology among (betaalpha)(8) barrels: implications for the evolution of metabolic pathways. , 2000, Journal of molecular biology.

[34]  I. Longden,et al.  EMBOSS: the European Molecular Biology Open Software Suite. , 2000, Trends in genetics : TIG.

[35]  D. Hartl,et al.  Solvent accessibility and purifying selection within proteins of Escherichia coli and Salmonella enterica. , 2000, Molecular biology and evolution.

[36]  中尾 光輝,et al.  KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース) , 2000 .

[37]  Z. Yang,et al.  Estimating synonymous and nonsynonymous substitution rates under realistic evolutionary models. , 2000, Molecular biology and evolution.

[38]  S. Lindquist,et al.  Hsp90 as a capacitor for morphological evolution , 1998, Nature.

[39]  David C. Jones,et al.  Assessing the impact of secondary structure and solvent accessibility on protein evolution. , 1998, Genetics.

[40]  A. Horwich,et al.  Structure and function in GroEL-mediated protein folding. , 1998, Annual review of biochemistry.

[41]  S. Lindquist,et al.  In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[42]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[43]  T. Creighton,et al.  Conformational specificity of the chaperonin GroEL for the compact folding intermediates of alpha‐lactalbumin. , 1994, The EMBO journal.

[44]  H. Mori,et al.  Effects of reduced levels of GroE chaperones on protein metabolism: enhanced synthesis of heat shock proteins during steady-state growth of Escherichia coli , 1994, Journal of bacteriology.

[45]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[46]  S. B. Needleman,et al.  A general method applicable to the search for similarities in the amino acid sequence of two proteins. , 1970, Journal of molecular biology.