David's theory of evolution: God's error corrections IV (Evolution)

by David Turell @, Thursday, October 22, 2020, 18:06 (359 days ago) @ David Turell
edited by David Turell, Thursday, October 22, 2020, 18:40

Correcting DNA base mismatches:


"There is a key difference between a mutation and a mismatch, even though both involve changing the identity of a nucleotide. A mutation occurs on both strands of the DNA double helix. This means that base-pairing between the DNA bases on each strand is maintained. A mismatch, however, occurs on only one strand, and so normal base-pairing is abolished. In normal base-pairing, adenine (A) bases on one strand of the DNA duplex pair with thymine (T) on the complementary strand, and guanine (G) bases pair with cytosine (C) — so a change from an A–T pair to a C–G pair is a mutation, whereas a change to A–C is a mismatch. Because mismatches are not base-paired, they can distort the overall structure of the DNA more easily than mutations can.

"It would be reasonable to assume that distortion of DNA would impair protein binding, but in fact it can contribute to binding specificity, through a mechanism known as shape readout. In simple terms, shape readout is the ability of proteins to indirectly recognize specific DNA sequences by their characteristic 3D shapes2,3. This is in contrast to their ability to directly recognize specific sequences by the characteristic chemical groups present in each base pair, a mechanism known as base readout. DNA is often thought of as having the same shape, regardless of its sequence, but shape readout works because this is not strictly true. Each sequence has a preferred set of conformations (called its conformational ensemble) and can be more- or less-easily bent in different ways. Taking advantage of this, a protein that needs to bind to a specific sequence can try to bend any sequence it encounters in a way that would be most compatible with its intended target. Because bending DNA has an energetic cost, this mechanism leads to a decrease in binding affinity.


"The authors therefore developed what they call a saturation mismatch-binding assay (SaMBA), which quantifies the binding of a protein to every possible single-nucleotide mismatch in a particular DNA sequence.


"SaMBA revealed not only that it is possible for mismatches to improve DNA–protein binding, but also that it is relatively common for them to do so. About 10% of all mismatches that Afek and colleagues analysed increased the affinity with which a protein bound to that sequence, including at least one such sequence for every protein. For some proteins, the most effective mismatch occurred in the natural target sequence, making the protein bind to that sequence even more tightly. For others, the most effective mismatch occurred in a non-target sequence, and made the protein bind to that sequence at levels comparable to those of the natural target."

Comment: Just presenting another example of God providing a check on DNA errors and making them actually useful! So not all errors are only bad as dhw, in denigrating God, is wont to write. God gave us the best living system He could.

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