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TUMOR FORMATION. "Genomic instability refers to an increased tendency of alterations in the genome during the life cycle of cells. It is a major driving force for tumorigenesis." https://lnkd.in/bam9PGn View in LinkedIn

AMPLIFICATION EFFECT. "Here is a stunning example of the consequences of RNA polymerase error rates. Tens of millions of humans are infected with HIV-1, and every infected person produces billions of viral genomes per day, each with one mutation. Over 10(16) genomes are produced daily on the entire planet. As a consequence, thousands of mutants arise by chance every day that are resistant to every combination of antiviral compounds in use or in development." https://lnkd.in/e9SMJNz View in LinkedIn

RNA VIRUS MUTATION RATE. "Given a typical RNA viral genome of 10,000 bases, a mutation frequency of 1 in 10,000 corresponds to an average of 1 mutation in every replicated genome. If a single cell infected with poliovirus produces 10,000 new virus particles, this error rate means that in theory, about 10,000 new viral mutants have been produced. This enormous mutation rate explains why RNA viruses evolve so readily." https://lnkd.in/e9SMJNz View in LinkedIn

KINGS OF ERRORS. "Even though DNA polymerases have proofreading abilities, they still make mistakes – on the order of about one misincorporation per 10(7) to 10(9) nucleotides polymerized. But the RNA polymerases of RNA viruses are the kings of errors – these enzymes screw up as often as one time for every 1,000 – 100,000 nucleotides polymerized. This high rate of mutation comes from the lack of proofreading ability in RNA polymerases." https://lnkd.in/e9SMJNz View in LinkedIn

ERROR CONTROL. "Most polymerases lack intrinsic error-checking activity, relying on Watson–Crick base pairing for their fidelity. However, the proofreading (exonuclease) domains of Pol δ and Pol ɛ ensure that these polymerases have a particularly low error rate, of the order of 10(-7) substitution mutations per base. A variety of in vitro studies has shown that proofreading improves replication fidelity approximately 100-fold." https://lnkd.in/eXdfD76 View in LinkedIn

SO ENDS the contemplation of protein diversity on planet earth, the most common proteins, and the number of sequences experimented with by Evolution since life began. And how relatively few templates can give rise to startling diversity of protein structures, and how they in turn collaborate into yet more structures. This is surely a snapshot of an evolutionary machine of extraordinary wit and ingenuity. View in LinkedIn

RATIONAL DISCUSSION. "We conclude that the number 20(100) and similar large numbers are simply ‘straw men’ advanced to initiate discussion in the same spirit as the ‘Levinthal paradox’ of protein folding rates. We hope that our calculation will also rule out any possible use of this big numbers ‘game’ to provide justification for postulating divine intervention." https://lnkd.in/eyPrQUq View in LinkedIn

VIRAL GENOME EDITING AS EVOLUTIONARY DRIVERS. "These competences integrate the whole toolbox of natural genetic engineering, replication, transcription, translation, genomic imprinting, genomic creativity, enzymatic inventions and all types of genetic repair patterns." https://lnkd.in/e-pJFM6 View in LinkedIn

PLANETARY TOTAL. "For comparison with our calculation, Mandecki (1998) gave a limit of 10(50) protein sequences since the origin of life... (In contrast) we arrive at a figure of 4×10(21) different protein sequences tested since the origin of life." https://lnkd.in/eyPrQUq View in LinkedIn

PRECISE EDITING. "It is becoming increasingly evident that the driving forces of evolutionary novelty are not randomly derived chance mutations of the genetic text, but a precise genome editing by omnipresent viral agents." An extraordinary statement to wrap your mind around, and contrary to previous thinking. Re-read and re-digest. https://lnkd.in/e-pJFM6 View in LinkedIn