title: Adaptive evolution of complex innovations through stepwise metabolic niche expansion.
abstract: A central challenge in evolutionary biology concerns the mechanisms by which complex metabolic innovations requiring multiple mutations arise. Here, we propose that metabolic innovations accessible through the addition of a single reaction serve as stepping stones towards the later establishment of complex metabolic features in another environment. We demonstrate the feasibility of this hypothesis through three complementary analyses. First, using genome-scale metabolic modelling, we show that complex metabolic innovations in Escherichia coli can arise via changing nutrient conditions. Second, using phylogenetic approaches, we demonstrate that the acquisition patterns of complex metabolic pathways during the evolutionary history of bacterial genomes support the hypothesis. Third, we show how adaptation of laboratory populations of E. coli to one carbon source facilitates the later adaptation to another carbon source. Our work demonstrates how complex innovations can evolve through series of adaptive steps without the need to invoke non-adaptive processes.
authors.affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Szappanos
authors.affiliation: Department for Computer Science, Heinrich Heine University, Universitätsstraße 1, Düsseldorf D-40221, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fritzemeier
authors.affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Csörgő
authors.affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Lázár
authors.affiliation: Department of Bioinformatics (CMBI), Radboud University Medical Centre, Geert Grooteplein Zuid 26-28, Nijmegen 6525 GA, The Netherlands.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Lu
authors.affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Fekete
authors.affiliation: SeqOmics Biotechnology Ltd, Vállalkozók útja 7, Mórahalom H-6782, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Bálint
authors.affiliation: SeqOmics Biotechnology Ltd, Vállalkozók útja 7, Mórahalom H-6782, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Herczeg
authors.affiliation: SeqOmics Biotechnology Ltd, Vállalkozók útja 7, Mórahalom H-6782, Hungary.|Sequencing Platform, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Nagy
authors.affiliation: Department of Bioinformatics (CMBI), Radboud University Medical Centre, Geert Grooteplein Zuid 26-28, Nijmegen 6525 GA, The Netherlands.|Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, Nijmegen 6525 GA, The Netherlands.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Notebaart
authors.affiliation: Department for Computer Science, Heinrich Heine University, Universitätsstraße 1, Düsseldorf D-40221, Germany.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lercher
authors.affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Pál
authors.affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Papp
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D005075:Biological Evolution; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008957:Models, Genetic