Efficient inefficiency: biochemical "junk" may represent molecular bridesmaids awaiting emergent function as a buffer against environmental fluctuation.
The biochemical function of many parts of the genome, transcriptome, proteome, and interactome remain largely unknown. We propose that portions of these fundamental building blocks of life have no current biochemical function per se. Rather, sections of these "omes" may contribute to an inventory of biochemical parts and circuits that participate in the development of emergent functions. Low fidelity deoxyribonucleic acid replication, transcription, translation, and post-translational modification all represent potential mechanisms to produce an inventory of parts. Stochastic processes that influence the conformations of ribonucleic acid molecules and proteins may also contribute to potential biochemical inventory. Some components of the biochemical inventory may enable future adaptations, some may produce disease, and some may remain useless. The function of many of these components await discovery, not by science, but by evolution. While carrying such purposeless biochemical units may appear to dilute fitness by exacting a thermodynamic cost, we argue that net fitness becomes enhanced when considering the value for potential future innovations. One can envision components that intermingle, interact, and act out mock pathways, but in most cases remain molecular bridesmaids. Given sufficiently low thermodynamic cost, such stochastic cycling may persist until a markedly advantageous or cataclysmically disadvantageous trait emerges. Maladaptive screening and utilization of inventory content can lead to disease phenotypes, a process buffered and regulated in part by the heat shock protein and stress response network. Whereas failure of the ubiquitin pathway to recycle misfolded proteins has become increasingly recognized as a source of disease, protein misfolding may itself represent one step in a process that maximizes functional innovation through increasing proteomic diversity. Fractal correlates of these processes occur at the organizational level of cells and organisms. That the abnormal accumulation of units induces local collapse may serve to limit the extension of damage to the greater system at large. The immune and cognitive systems that selectively sample and prune environmental content may serve as additional portals for innovation.
Yun
Anthony J
AJ
Stanford University, Radiology, 470 University Avenue, Palo Alto, CA 94301, United States. ayun@stanford.edu <ayun@stanford.edu>
Lee
Patrick Y
PY
Doux
John D
JD
D000222:Adaptation, Physiological; D000818:Animals; D004777:Environment; D019143:Evolution, Molecular; D017709:Fractals; D016678:Genome; D015894:Genome, Human; D006360:Heat-Shock Proteins / Q000502:physiology; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000502:physiology; D020543:Proteome; D012641:Selection, Genetic; D013269:Stochastic Processes; D013816:Thermodynamics; D014158:Transcription, Genetic
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020543:Proteome