ALBERT

Description: In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681099/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681099/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forslund, Kristoffer -- Hildebrand, Falk -- Nielsen, Trine -- Falony, Gwen -- Le Chatelier, Emmanuelle -- Sunagawa, Shinichi -- Prifti, Edi -- Vieira-Silva, Sara -- Gudmundsdottir, Valborg -- Krogh Pedersen, Helle -- Arumugam, Manimozhiyan -- Kristiansen, Karsten -- Voigt, Anita Yvonne -- Vestergaard, Henrik -- Hercog, Rajna -- Igor Costea, Paul -- Kultima, Jens Roat -- Li, Junhua -- Jorgensen, Torben -- Levenez, Florence -- Dore, Joel -- MetaHIT consortium -- Nielsen, H Bjorn -- Brunak, Soren -- Raes, Jeroen -- Hansen, Torben -- Wang, Jun -- Ehrlich, S Dusko -- Bork, Peer -- Pedersen, Oluf -- England -- Nature. 2015 Dec 10;528(7581):262-6. doi: 10.1038/nature15766. Epub 2015 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany. ; VIB Center for the Biology of Disease, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. ; Department of Bioscience Engineering, Vrije Universiteit Brussel, 1040 Brussels, Belgium. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ; Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. ; MICALIS, Institut National de la Recherche Agronomique, 78352 Jouy en Josas, France. ; Metagenopolis, Institut National de la Recherche Agronomique, 78352 Jouy en Josas, France. ; Institute of Cardiometabolism and Nutrition, 75013 Paris, France. ; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. ; Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark. ; Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany. ; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany. ; Bejing Genomics Institute (BGI)-Shenzhen, 518083 Shenzhen, China. ; Research Centre for Prevention and Health, Capital Region of Denmark, 2600 Glostrup, Denmark. ; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 2600 Copenhagen, Denmark. ; Faculty of Medicine, University of Aalborg, 9100 Aalborg, Denmark. ; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ; Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark. ; Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, 80205 Jeddah, Saudi Arabia. ; Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. ; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong. ; Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, King's College London, London SE1 9RT , UK. ; Max Delbruck Centre for Molecular Medicine, 13125 Berlin, Germany. ; Department of Bioinformatics, University of Wuerzburg, 97074 Wurzburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26633628" target="_blank"〉PubMed〈/a〉

Description: Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with 〉40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing 〉35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that 〉73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sunagawa, Shinichi -- Coelho, Luis Pedro -- Chaffron, Samuel -- Kultima, Jens Roat -- Labadie, Karine -- Salazar, Guillem -- Djahanschiri, Bardya -- Zeller, Georg -- Mende, Daniel R -- Alberti, Adriana -- Cornejo-Castillo, Francisco M -- Costea, Paul I -- Cruaud, Corinne -- d'Ovidio, Francesco -- Engelen, Stefan -- Ferrera, Isabel -- Gasol, Josep M -- Guidi, Lionel -- Hildebrand, Falk -- Kokoszka, Florian -- Lepoivre, Cyrille -- Lima-Mendez, Gipsi -- Poulain, Julie -- Poulos, Bonnie T -- Royo-Llonch, Marta -- Sarmento, Hugo -- Vieira-Silva, Sara -- Dimier, Celine -- Picheral, Marc -- Searson, Sarah -- Kandels-Lewis, Stefanie -- Tara Oceans coordinators -- Bowler, Chris -- de Vargas, Colomban -- Gorsky, Gabriel -- Grimsley, Nigel -- Hingamp, Pascal -- Iudicone, Daniele -- Jaillon, Olivier -- Not, Fabrice -- Ogata, Hiroyuki -- Pesant, Stephane -- Speich, Sabrina -- Stemmann, Lars -- Sullivan, Matthew B -- Weissenbach, Jean -- Wincker, Patrick -- Karsenti, Eric -- Raes, Jeroen -- Acinas, Silvia G -- Bork, Peer -- New York, N.Y. -- Science. 2015 May 22;348(6237):1261359. doi: 10.1126/science.1261359.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; CEA-Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91057 Evry, France. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. ; Sorbonne Universites, UPMC, Universite Paris 06, CNRS-IRD-MNHN, LOCEAN Laboratory, 4 Place Jussieu, 75005 Paris France. ; CNRS, UMR 7093, Laboratoire d'Oceanographie de Villefranche-sur-Mer, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7093, LOV, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. Laboratoire de Physique des Oceans UBO-IUEM, Place Copernic 29820 Plouzane, France. ; Aix Marseille Universite CNRS IGS UMR 7256, 13288 Marseille, France. ; Department of Ecology and Evolutionary Biology, University of Arizona, 1007 East Lowell Street, Tucson, AZ 85721, USA. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. Department of Hydrobiology, Federal University of Sao Carlos (UFSCar), Rodovia Washington Luiz, 13565-905 Sao Carlos, Sao Paulo, Brazil. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; CNRS UMR 7232, BIOM, Avenue du Fontaule, 66650 Banyuls-sur-Mer, France. Sorbonne Universites Paris 06, OOB UPMC, Avenue du Fontaule, 66650 Banyuls-sur-Mer, France. ; Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy. ; CEA-Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91057 Evry, France. CNRS, UMR 8030, CP5706, Evry, France. Universite d'Evry, UMR 8030, CP5706, Evry, France. ; Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, 611-001, Japan. ; PANGAEA, Data Publisher for Earth and Environmental Science, University of Bremen, Bremen, Germany. MARUM, Center for Marine Environmental Sciences, University of Bremen, Bremen, Germany. ; Department of Geosciences, Laboratoire de Meteorologie Dynamique (LMD), Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris Cedex 05, France. Laboratoire de Physique des Oceans UBO-IUEM, Place Copernic, 29820 Plouzane, France. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Max-Delbruck-Centre for Molecular Medicine, 13092 Berlin, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999513" target="_blank"〉PubMed〈/a〉

Description: Fecal microbiome variation in the average, healthy population has remained under-investigated. Here, we analyzed two independent, extensively phenotyped cohorts: the Belgian Flemish Gut Flora Project (FGFP; discovery cohort; N = 1106) and the Dutch LifeLines-DEEP study (LLDeep; replication; N = 1135). Integration with global data sets (N combined = 3948) revealed a 14-genera core microbiota, but the 664 identified genera still underexplore total gut diversity. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92% replication rate. Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations. Early-life events such as birth mode were not reflected in adult microbiota composition. Finally, we found that proposed disease marker genera associated to host covariates, urging inclusion of the latter in study design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Falony, Gwen -- Joossens, Marie -- Vieira-Silva, Sara -- Wang, Jun -- Darzi, Youssef -- Faust, Karoline -- Kurilshikov, Alexander -- Bonder, Marc Jan -- Valles-Colomer, Mireia -- Vandeputte, Doris -- Tito, Raul Y -- Chaffron, Samuel -- Rymenans, Leen -- Verspecht, Chloe -- De Sutter, Lise -- Lima-Mendez, Gipsi -- D'hoe, Kevin -- Jonckheere, Karl -- Homola, Daniel -- Garcia, Roberto -- Tigchelaar, Ettje F -- Eeckhaudt, Linda -- Fu, Jingyuan -- Henckaerts, Liesbet -- Zhernakova, Alexandra -- Wijmenga, Cisca -- Raes, Jeroen -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):560-4. doi: 10.1126/science.aad3503. Epub 2016 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. ; KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium. ; Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. Novosibirsk State University, Novosibirsk, Russia. ; University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, Netherlands. ; VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium. ; University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands. ; University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Department of Pediatrics, 9700 RB Groningen, Netherlands. ; KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. KU Leuven-University Hospitals Leuven, Department of General Internal Medicine, Leuven, Belgium. ; KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium. jeroen.raes@kuleuven.be.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126039" target="_blank"〉PubMed〈/a〉

Description: Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These factors collectively explain 18.7% of the variation seen in the interindividual distance of microbial composition. We could associate 110 factors to 125 species and observed that fecal chromogranin A (CgA), a protein secreted by enteroendocrine cells, was exclusively associated with 61 microbial species whose abundance collectively accounted for 53% of microbial composition. Low CgA concentrations were seen in individuals with a more diverse microbiome. These results are an important step toward a better understanding of environment-diet-microbe-host interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhernakova, Alexandra -- Kurilshikov, Alexander -- Bonder, Marc Jan -- Tigchelaar, Ettje F -- Schirmer, Melanie -- Vatanen, Tommi -- Mujagic, Zlatan -- Vila, Arnau Vich -- Falony, Gwen -- Vieira-Silva, Sara -- Wang, Jun -- Imhann, Floris -- Brandsma, Eelke -- Jankipersadsing, Soesma A -- Joossens, Marie -- Cenit, Maria Carmen -- Deelen, Patrick -- Swertz, Morris A -- LifeLines cohort study -- Weersma, Rinse K -- Feskens, Edith J M -- Netea, Mihai G -- Gevers, Dirk -- Jonkers, Daisy -- Franke, Lude -- Aulchenko, Yurii S -- Huttenhower, Curtis -- Raes, Jeroen -- Hofker, Marten H -- Xavier, Ramnik J -- Wijmenga, Cisca -- Fu, Jingyuan -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):565-9. doi: 10.1126/science.aad3369. Epub 2016 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl. ; Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. Novosibirsk State University, Novosibirsk, Russia. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands. ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Computer Science, Aalto University School of Science, Espoo, Finland. ; Top Institute Food and Nutrition, Wageningen, Netherlands. Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands. ; University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, Netherlands. ; KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. ; University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands. ; KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Microbial Ecology, Nutrition and Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain. Department of Pediatrics, Dr. Peset University Hospital, Valencia, Spain. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, Netherlands. ; Top Institute Food and Nutrition, Wageningen, Netherlands. Division of Human Nutrition, Wageningen University, Wageningen, Netherlands. ; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands. ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. ; Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands. ; Novosibirsk State University, Novosibirsk, Russia. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. PolyOmica, Groningen, Netherlands. Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia. ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126040" target="_blank"〉PubMed〈/a〉

Description: Proteins evolve at very different rates and, most notably, at rates inversely proportional to the level at which they are produced. The relative frequency of highly expressed proteins in the proteome, and thus their impact on the cell budget, increases steeply with growth rate. The maximal growth rate is a key life-history trait reflecting trade-offs between rapid growth and other fitness components. We show that the maximal growth rate is weakly affected by genetic drift. The negative correlation between protein expression levels and evolutionary rate and the positive correlation between expression levels of highly expressed proteins and growth rates, suggest that investment in growth affects the evolutionary rate of proteins, especially the highly expressed ones. Accordingly, analysis of 61 families of orthologs in 74 proteobacteria shows that differences in evolutionary rates between lowly and highly expressed proteins depend on maximal growth rates. Analyses of complexes with key roles in bacterial growth and strikingly different expression levels, the ribosome and the replisome, confirm these patterns and suggest that the growth-related sequence conservation is associated with protein synthesis. Maximal growth rates also shape protein evolution in the other bacterial clades. Long-branch attractions associated with this effect might explain why clades with persistent history of slow growth are attracted to the root when the tree of prokaryotes is inferred using highly, but not lowly, expressed proteins. These results indicate that reconstruction of deep phylogenies can be strongly affected by maximal growth rates, and highlight the importance of life-history traits and their physiological consequences for protein evolution.