title: Systems level analysis of the Chlamydomonas reinhardtii metabolic network reveals variability in evolutionary co-conservation.
abstract: Metabolic networks, which are mathematical representations of organismal metabolism, are reconstructed to provide computational platforms to guide metabolic engineering experiments and explore fundamental questions on metabolism. Systems level analyses, such as interrogation of phylogenetic relationships within the network, can provide further guidance on the modification of metabolic circuitries. Chlamydomonas reinhardtii, a biofuel relevant green alga that has retained key genes with plant, animal, and protist affinities, serves as an ideal model organism to investigate the interplay between gene function and phylogenetic affinities at multiple organizational levels. Here, using detailed topological and functional analyses, coupled with transcriptomics studies on a metabolic network that we have reconstructed for C. reinhardtii, we show that network connectivity has a significant concordance with the co-conservation of genes; however, a distinction between topological and functional relationships is observable within the network. Dynamic and static modes of co-conservation were defined and observed in a subset of gene-pairs across the network topologically. In contrast, genes with predicted synthetic interactions, or genes involved in coupled reactions, show significant enrichment for both shorter and longer phylogenetic distances. Based on our results, we propose that the metabolic network of C. reinhardtii is assembled with an architecture to minimize phylogenetic profile distances topologically, while it includes an expansion of such distances for functionally interacting genes. This arrangement may increase the robustness of C. reinhardtii's network in dealing with varied environmental challenges that the species may face. The defined evolutionary constraints within the network, which identify important pairings of genes in metabolism, may offer guidance on synthetic biology approaches to optimize the production of desirable metabolites.
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu.
authors.forename: Amphun
authors.initials: A
authors.lastname: Chaiboonchoe
authors.affiliation: Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: Lila
authors.initials: L
authors.lastname: Ghamsari
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu.
authors.forename: Bushra
authors.initials: B
authors.lastname: Dohai
authors.affiliation: Department of Biological Statistics and Computational Biology and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA. haiyuan.yu@cornell.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ng
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu.
authors.forename: Basel
authors.initials: B
authors.lastname: Khraiwesh
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu.
authors.forename: Ashish
authors.initials: A
authors.lastname: Jaiswal
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu.
authors.forename: Kenan
authors.initials: K
authors.lastname: Jijakli
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Koussa
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.affiliation: Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: Xinping
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Chang
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. papin@virginia.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Papin
authors.affiliation: Department of Biological Statistics and Computational Biology and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA. haiyuan.yu@cornell.edu.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Yu
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu and Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA, USA and MRC Laboratory of Molecular Biology, Cambridge, UK. bsanthan@mrc-lmb.cam.ac.uk.
authors.forename: Santhanam
authors.initials: S
authors.lastname: Balaji
authors.affiliation: Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York University Abu Dhabi and Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi, UAE. ksa3@nyu.edu and Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Salehi-Ashtiani
mesh_terms: D005075:Biological Evolution; D016825:Chlamydomonas reinhardtii / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods; D053858:Metabolic Networks and Pathways; D016366:Open Reading Frames / Q000235:genetics; D058615:Synthetic Biology / Q000379:methods