Genome complexity: evidence of non-random mutation (Introduction)

by David Turell @, Wednesday, March 16, 2022, 17:04 (743 days ago) @ David Turell

Another article on humans:

https://genome.cshlp.org/content/early/2022/01/14/gr.276103.121

"Abstract:
While it is known that the mutation rate varies across the genome, previous estimates were based on averaging across various numbers of positions. Here we describe a method to measure the origination rates of target mutations at target base positions and apply it to a 6-bp region in the human hemoglobin subunit beta (HBB) gene and to the identical, paralogous hemoglobin subunit delta (HBD) region in sperm cells from both African and European donors. The HBB region of interest (ROI) includes the site of the hemoglobin S (HbS) mutation, which protects against malaria, is common in Africa and has served as a classic example of adaptation by random mutation and natural selection. We found a significant correspondence between de novo mutation rates and past observations of alleles in carriers, showing that mutation rates vary substantially in a mutation-specific manner that contributes to the site frequency spectrum. We also found that the overall point mutation rate is significantly higher in Africans than in Europeans in the HBB region studied. Finally, the rate of the 20A→T mutation, called the 'HbS mutation' when it appears in HBB, is significantly higher than expected from the genome-wide average for this mutation type. Nine instances were observed in the African HBB ROI, where it is of adaptive significance, representing at least three independent originations; no instances were observed elsewhere. Further studies will be needed to examine mutation rates at the single-mutation resolution across these and other loci and organisms and to uncover the molecular mechanisms responsible." (my bold)

From a review of the article:

https://www.eurekalert.org/news-releases/941828

"A new study by a team of researchers from Israel and Ghana has brought the first evidence of nonrandom mutation in human genes, challenging a core assumption at the heart of evolutionary theory by showing a long-term directional mutational response to environmental pressure. Using a novel method, researchers led by Professor Adi Livnat from the University of Haifa showed that the rate of generation of the HbS mutation, which protects against malaria, is higher in people from Africa, where malaria is endemic, than in people from Europe

"The results show that the HbS mutation is not generated at random but instead originates preferentially in the gene and in the population where it is of adaptive significance,” said Prof. Livnat. Unlike other findings on mutation origination, this mutation-specific response to a specific environmental pressure cannot be explained by traditional theories. “We hypothesize that evolution is influenced by two sources of information: external information that is natural selection, and internal information that is accumulated in the genome through the generations and impacts the origination of mutations,” said Livnat.

***

"Contrary to the widely accepted expectations, the results supported the nonrandom pattern. The HbS mutation originated de novo not only much faster than expected from random mutation, but also much faster in the population (in sub-Saharan Africans as opposed to Europeans) and in the gene (in the beta-globin as opposed to the control delta-globin gene) where it is of adaptive significance. These results upend the traditional example of random mutation and natural selection, turning it into an example of a nonrandom yet non-Lamarckian mutation. (my bold)

***

"Previous studies, motivated by Lamarckism, only tested for an immediate mutational response to environmental pressures. “Mutations may be generated nonrandomly in evolution after all, but not in the way previously conceived. We must study the internal information and how it affects mutation, as it opens the door to evolution being a far bigger process than previously conceived,” Livnat concluded.

"Until now, investigators have been limited by technology to measuring mutation rates as averages across many positions in the genome. Overcoming this barrier, the new method developed by Livnat and Melamed allowed the HbS mutation to be the first to have its mutation-specific origination rate measured, opening up new vistas for studies on mutation origination. These studies have the potential to affect not only our fundamental understanding of evolution, but also our understanding of diseases that are caused by mutations, namely genetic disease and cancer." (my bold)

Comment: Wow! Here we see just the mechanism dhw proposes in a very specific limited example, changing hemoglobin into form malaria cannot enter. And it doesn't seem a chance random mutation. But this is not at the level of complex phenotypical or physiological design dhw wants God to give organisms.


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