Determinism and contingency shape metabolic complementation in an endosymbiotic consortium

Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism-which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca. Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome-scale metabolic network (GEM) for the bacterial consortium from the cedar aphid iBSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with iBSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is significant in the case of tryptophan biosynthesis, whereas vitamin production pathways seem to adopt suboptimal solutions.We would like to thank the Obra Social Programme of La Caixa Savings Bank for the doctoral fellowship granted to JC-E. Financial support from Spanish Government (grant reference: BFU2015-64322-C2-1-R co-financed by FEDER funds and Ministerio de Economía y Competitividad) and Generalitat Valenciana (grant reference: PROMETEOII/2014/065) is gratefully acknowledged. MM acknowledges financial support from Sapienza, University of Rome. DT acknowledges support by a European Union grant from the Marie Curie ITN SYMBIOMICS (264774) and a grant from the Knut and Alice Wallenberg Foundation (2012.0075), given to Björn Andersson (Karolinska Institute) and Siv Andersson (Uppsala University).Peer reviewe