title: Comparative functional pan-genome analyses to build connections between genomic dynamics and phenotypic evolution in polycyclic aromatic hydrocarbon metabolism in the genus Mycobacterium.
abstract: BACKGROUND
  The bacterial genus Mycobacterium is of great interest in the medical and biotechnological fields. Despite a flood of genome sequencing and functional genomics data, significant gaps in knowledge between genome and phenome seriously hinder efforts toward the treatment of mycobacterial diseases and practical biotechnological applications. In this study, we propose the use of systematic, comparative functional pan-genomic analysis to build connections between genomic dynamics and phenotypic evolution in polycyclic aromatic hydrocarbon (PAH) metabolism in the genus Mycobacterium.
  
  
  RESULTS
  Phylogenetic, phenotypic, and genomic information for 27 completely genome-sequenced mycobacteria was systematically integrated to reconstruct a mycobacterial phenotype network (MPN) with a pan-genomic concept at a network level. In the MPN, mycobacterial phenotypes show typical scale-free relationships. PAH degradation is an isolated phenotype with the lowest connection degree, consistent with phylogenetic and environmental isolation of PAH degraders. A series of functional pan-genomic analyses provide conserved and unique types of genomic evidence for strong epistatic and pleiotropic impacts on evolutionary trajectories of the PAH-degrading phenotype. Under strong natural selection, the detailed gene gain/loss patterns from horizontal gene transfer (HGT)/deletion events hypothesize a plausible evolutionary path, an epistasis-based birth and pleiotropy-dependent death, for PAH metabolism in the genus Mycobacterium. This study generated a practical mycobacterial compendium of phenotypic and genomic changes, focusing on the PAH-degrading phenotype, with a pan-genomic perspective of the evolutionary events and the environmental challenges.
  
  
  CONCLUSIONS
  Our findings suggest that when selection acts on PAH metabolism, only a small fraction of possible trajectories is likely to be observed, owing mainly to a combination of the ambiguous phenotypic effects of PAHs and the corresponding pleiotropy- and epistasis-dependent evolutionary adaptation. Evolutionary constraints on the selection of trajectories, like those seen in PAH-degrading phenotypes, are likely to apply to the evolution of other phenotypes in the genus Mycobacterium.
authors.affiliation: Division of Microbiology, National Center for Toxicological Research/FDA, Jefferson, Arkansas, USA. oh-gew.kweon@fda.hhs.gov.
authors.forename: Ohgew
authors.initials: O
authors.lastname: Kweon
authors.affiliation: Division of Microbiology, National Center for Toxicological Research/FDA, Jefferson, Arkansas, USA. Seong-Jae.Kim@fda.hhs.gov.
authors.forename: Seong-Jae
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Center for Biotechnology, Bielefeld University, Bielefeld, Nordrhein-Westfalen, Germany. Jochen.Blom@computational.bio.uni-giessen.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Blom
authors.affiliation: Department of Management, University of Arkansas at Little Rock, Little Rock, Arkansas, USA. sxkim@ualr.edu.
authors.forename: Sung-Kwan
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Life Science, Hallym University, Chuncheon, Gangwon-do, 200-702, Republic of Korea. bongsoo.km@gmail.com.
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Dankook University, Chonan, Republic of Korea. micro94@gmail.com.
authors.forename: Dong-Heon
authors.initials: DH
authors.lastname: Baek
authors.affiliation: Department of Computer Science and Engineering, Texas A&M University, College Station, Texas, USA. joshsuihn@gmail.com.
authors.forename: Su Inn
authors.initials: SI
authors.lastname: Park
authors.affiliation: Division of Microbiology, National Center for Toxicological Research/FDA, Jefferson, Arkansas, USA. John.Sutherland@fda.hhs.gov.
authors.forename: John B
authors.initials: JB
authors.lastname: Sutherland
authors.affiliation: Division of Microbiology, National Center for Toxicological Research/FDA, Jefferson, Arkansas, USA. carl.cerniglia@fda.hhs.gov.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Cerniglia
mesh_terms: D001673:Biodegradation, Environmental; D005075:Biological Evolution; D004843:Epistasis, Genetic; D022761:Gene Transfer, Horizontal; D005798:Genes, Bacterial; D023281:Genomics; D009161:Mycobacterium / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons