title: Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life.
abstract: Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the "minimal" synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life.
authors.affiliation: Laboratory of Systems and Synthetic Biology, Department of Agrotechnology and Food Sciences, Wageningen University and ResearchWageningen, Netherlands; Bioprocess Technology and Support, MSD Animal HealthBoxmeer, Netherlands.
authors.forename: Tjerko
authors.initials: T
authors.lastname: Kamminga
authors.affiliation: Laboratory of Systems and Synthetic Biology, Department of Agrotechnology and Food Sciences, Wageningen University and Research Wageningen, Netherlands.
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Koehorst
authors.affiliation: Discovery and Technology, MSD Animal Health Boxmeer, Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Vermeij
authors.affiliation: Bioprocess Technology and Support, MSD Animal Health Boxmeer, Netherlands.
authors.forename: Simen-Jan
authors.initials: SJ
authors.lastname: Slagman
authors.affiliation: Laboratory of Systems and Synthetic Biology, Department of Agrotechnology and Food Sciences, Wageningen University and Research Wageningen, Netherlands.
authors.forename: Vitor A P
authors.initials: VA
authors.lastname: Martins Dos Santos
authors.affiliation: Discovery and Technology, MSD Animal Health Boxmeer, Netherlands.
authors.forename: Jetta J E
authors.initials: JJ
authors.lastname: Bijlsma
authors.affiliation: Laboratory of Systems and Synthetic Biology, Department of Agrotechnology and Food Sciences, Wageningen University and Research Wageningen, Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schaap
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D005798:Genes, Bacterial; D059646:Genome Size; D016680:Genome, Bacterial / Q000235:genetics*; D058507:Host Specificity; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D009174:Mycoplasma / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D009175:Mycoplasma Infections; D010802:Phylogeny; D000072417:Protein Domains / Q000235:genetics* / Q000502:physiology*; D020543:Proteome; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013045:Species Specificity; D013149:Spiroplasma / Q000235:genetics / Q000502:physiology; D013552:Swine
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D012336:RNA, Ribosomal, 16S
keywords: genome comparison; host specificity; minimal genome; mollicutes; mycoplasma; niche specificity; protein domains; protein metabolism