Biochemistry

Deep salty RNA world

Authors: Warren D. Smith
Comments: 57 Pages. v3 adds new section discussing experiments that cast doubt on Hypothesis I - perhaps fatally.

I. HYPOTHESIS: Aqueous RNA becomes stable against hydrolysis under high hydrostatic pressure, 1-4000 atm. Weaker also-sufficient hypothesis: it works for some exponentially-large subset of RNA-like molecules; also salinity has most of the same beneficial effects as pressure, and both can work together. This and related hypotheses can resolve the gaping holes in L.E.Orgel's "RNA world" paradigm about life's origin. It deserves direct experimental tests, but even without them we present 4 independent lines of evidence for it apparently yielding confidence>99.9999%.

II. I explain how to measure the "true vital information content" of a lifeform. It is hugely wrong to claim an N-base pair DNA genome has information content 2N bits. The simplest estimate instead should be ≤-Nlog₂(1-3ε/4)∼3εN/ln16≈1.082εN bits, where ε is the chance that a random single-base mutation would kill the organism and experimentally for bacteria ε≈1%, and the "≤" is because of further refinements I'll describe, which can reduce the bit-count further. I explain how to get more precise estimates with more experimental and computational work. Then calculating numbers shows that the genesis of life was not necessarily absurdly improbable; predicted and observed genesis rates plausibly can roughly agree.

Together, ideas I (if correct) and II overcome the two top obstacles blocking understanding how genesis could have happened, and suggest many experiments. Unfortunately version 3 adds a new section "(Pessimistic) Post Mortem" which discusses another class experiments (on "apparent molar volumes") whose results suggest I is false.
Category: Biochemistry

Induction of de Novo Centriole Biogenesis in Planarian Stem Cells

Authors: Jaba Tkemaladze, Gabro Gakely
Comments: 19 Pages.

The centriole is a fundamental organelle templating cilia formation and ensuring genomic stability. While most cells assemble centrioles using a pre-existing mother as a template, the de novo pathway allows for assembly in their absence. However, the physiological role and regulation of de novo biogenesis in vivo remain poorly understood. The planarian Schmidtea mediterranea, with its abundant somatic stem cells (neoblasts) and dependence on a massive ciliated epithelium for locomotion, presents a unique model to address this gap. We demonstrate that quiescent neoblasts are acentriolar, lacking the templates for canonical duplication. Upon tissue injury, neoblasts are activated and initiate a programmed de novo centriole biogenesis pathway. Super-resolution microscopy and transmission electron microscopy reveal the formation of cytoplasmic procentriolar foci and mature centrioles, independent of any parental structure. Crucially, genetic ablation of Sas-6 or pharmacological inhibition of PLK4—interventions that effectively block the canonical pathway—fail to prevent the formation of new centrioles and functional basal bodies in the regenerating ciliated epithelium. This work provides the first in vivo evidence in a whole organism for an induced de novo centriole biogenesis pathway in adult somatic stem cells. We propose this pathway is a key evolutionary adaptation, enabling rapid, large-scale ciliogenesis essential for planarian regeneration, and represents a distinct, genetically regulated program separable from canonical duplication.
Category: Biochemistry