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Researchers: A mutational timer is built into DNA chemistry

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DNA contains a kind of built-in timer that clocks the frequency with which mutations occur/Al-Hashimi Lab, Duke University

From ScienceDaily:

Every time our cells divide, the DNA within them must replicate so that each new cell receives the same set of instructions. Molecular machines known as polymerases make these copies of DNA by recognizing the shape of the right base pair combinations — G with C and A with T — and adding them into each new double helix, while discarding those that don’t fit together correctly. Though they are good at their job, polymerases are known to slip up from time to time, generating a mistake roughly one out of every 10,000 bases. If not fixed these become immortalized in the genome as a mutation.

The study, published in a 2015 issue of Nature, showed the bases G and T nudging aside the atoms on their surface so they could connect like puzzle pieces. The researchers found that these rearrangements came in different varieties, called “tautomeric” and “anionic” forms, though it wasn’t clear which ones were responsible for replication errors.

In this [2018] study, Duke graduate students Isaac Kimsey and Eric Szymanski used an enhanced version of their previous technique to examine the relationship between these shape-shifting bases and the errors made by the DNA-copying polymerase. Again, they caught the G and T bases in the act, and showed that their shape-shifting occurred at about the same rate that polymerases incorporate G-T mismatches.

Together with their collaborators at The Ohio State University, they fed their NMR data into a “kinetic model” that traced the nearly invisible movements taken by the atoms in the mismatches that result in replication errors. They found that, though the different alternative states each contributed to errors, the tautomeric forms dominated under normal conditions and the anionic forms dominated in the presence of mutagens and environmental stress. Paper. (paywall) – Isaac J. Kimsey, Eric S. Szymanski, Walter J. Zahurancik, Anisha Shakya, Yi Xue, Chia-Chieh Chu, Bharathwaj Sathyamoorthy, Zucai Suo, Hashim M. Al-Hashimi. Dynamic basis for dG•dT misincorporation via tautomerization and ionization. Nature, 2018; DOI: 10.1038/nature25487 More.

The fact that errors occur only once in 10,000 times is, of course, completely consistent with a random origin and development of life. The debate is over. Randomness does wonders.

Note: “They found that, though the different alternative states each contributed to errors, the tautomeric forms dominated under normal conditions and the anionic forms dominated in the presence of mutagens and environmental stress.” Something to keep an eye on.

See also: Researchers: Mechanism may exist in all animals for filtering out mitochondrial DNA mutations

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Random changes in life forms are just as successful as random changes in typing!

One Reply to “Researchers: A mutational timer is built into DNA chemistry

  1. 1
    ronvanwegen says:

    Quote: “Though they are good at their job, polymerases are known to slip up from time to time, generating a mistake roughly one out of every 10,000 bases. If not fixed these become immortalized in the genome as a mutation.”

    Or, in other words… “If not fixed these become fixed!”

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