title: The Swine Plasma Metabolome Chronicles "Many Days" Biological Timing and Functions Linked to Growth.
abstract: The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien) chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA) drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the biological bases that regulate mammalian growth, body size, and life history.
authors.affiliation: Department of Biomaterials & Biomimetics, New York University College of Dentistry, New York, New York, United States of America.|Department of Basic Science & Craniofacial Biology, New York University College of Dentistry, New York, New York, United States of America.|Department of Palaeoanthropology, Senckenberg Research Institute, Frankfurt am Main, Germany.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Bromage
authors.affiliation: Department of Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Idaghdour
authors.affiliation: Department of Basic Science & Craniofacial Biology, New York University College of Dentistry, New York, New York, United States of America.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Lacruz
authors.affiliation: Department of Animal Science, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Crenshaw
authors.affiliation: Department of Biomaterials & Biomimetics, New York University College of Dentistry, New York, New York, United States of America.
authors.forename: Olexandra
authors.initials: O
authors.lastname: Ovsiy
authors.affiliation: GenXPro GmbH, Frankfurt am Main, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Rotter
authors.affiliation: GenXPro GmbH, Frankfurt am Main, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hoffmeier
authors.affiliation: Department of Palaeoanthropology, Senckenberg Research Institute, Frankfurt am Main, Germany.|Institute for Ecology, Evolution & Diversity, Goethe University, Frankfurt am Main, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Schrenk
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D003743:Dental Enamel / Q000254:growth & development; D005260:Female; D023281:Genomics; D055442:Metabolome; D055432:Metabolomics; D022661:RNA, Untranslated / Q000097:blood; D013552:Swine
chemical_list: D022661:RNA, Untranslated