title: A principle of organization which facilitates broad Lamarckian-like adaptations by improvisation.
abstract: BACKGROUND
  During the lifetime of an organism, every individual encounters many combinations of diverse changes in the somatic genome, epigenome and microbiome. This gives rise to many novel combinations of internal failures which are unique to each individual. How any individual can tolerate this high load of new, individual-specific scenarios of failure is not clear. While stress-induced plasticity and hidden variation have been proposed as potential mechanisms of tolerance, the main conceptual problem remains unaddressed, namely: how largely non-beneficial random variation can be rapidly and safely organized into net benefits to every individual.
  
  
  OBJECTIVE
  We propose an organizational principle which explains how every individual can alleviate a high load of novel stressful scenarios using many random variations in flexible and inherently less harmful traits. Random changes which happen to reduce stress, benefit the organism and decrease the drive for additional changes. This adaptation (termed 'Adaptive Improvisation') can be further enhanced, propagated, stabilized and memorized when beneficial changes reinforce themselves by auto-regulatory mechanisms. This principle implicates stress not only in driving diverse variations in cells tissues and organs, but also in organizing these variations into adaptive outcomes. Specific (but not exclusive) examples include stress reduction by rapid exchange of mobile genetic elements (or exosomes) in unicellular, and rapid changes in the symbiotic microorganisms of animals. In all cases, adaptive changes can be transmitted across generations, allowing rapid improvement and assimilation in a few generations.
  
  
  METHODS
  We provide testable predictions derived from the hypothesis.
  
  
  CONCLUSIONS
  The hypothesis raises a critical, but thus far overlooked adaptation problem and explains how random variation can self-organize to confer a wide range of individual-specific adaptations beyond the existing outcomes of natural selection. It portrays gene regulation as an inseparable synergy between natural selection and adaptation by improvisation. The latter provides a basis for Lamarckian adaptation that is not limited to a specific mechanism and readily accounts for the remarkable resistance of tumors to treatment.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel. yoavs@weizmann.ac.il.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Soen
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel. maor.knafo@weizmann.ac.il.
authors.forename: Maor
authors.initials: M
authors.lastname: Knafo
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel. elgart@gmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Elgart
mesh_terms: D000220:Adaptation, Biological; D044127:Epigenesis, Genetic; D008957:Models, Genetic; D010641:Phenotype; D012641:Selection, Genetic