Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the nonresistant but otherwise identical 20A→T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here, we address this finding with the replacement hypothesis, according to which preexisting genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, an evolutionary process under selection can gradually hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A→G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called interaction-based evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directed mutational responses to specific environmental pressures are possible. Such mutational phenomena need to be further tested by future studies in natural and artificial settings.
An informed colleague, not associated in any way with ID (so don’t take that rabbit trail) asked my opinion of this article.
Is there anything new here? We already know mutations do not occur with equal frequency across the genome, and that these frequency changes can change in response to selection. If mutation rates at a locus can be suppressed because they incur a stronger fitness cost there, then they can relieve such a suppressive effect too wherever it might occur.
This the potential claim being made that may be particular to this paper:
A third possibility, which we will focus on here, is that the HbS mutation originates in a manner that is neither accidental nor Lamarckian. According to this possibility, this mutation demonstrates a long-term directed mutational response to a specific environmental pressure (Livnat 2013, 2017).
I find their reasoning to be logically incoherent. A rise in the frequency of an adaptive mutation in a particular environment in which that mutation is adaptive, as a response to longer-term selection, does not make those mutations still occurring with some probability less than one hundred percent, “non-accidental.”
What is the frequency at which the occurrence of a particular mutation crosses over from “accidental” to “non-accidental”? It seems to me that as long as that mutation still occurs with some non-guaranteed frequency less than 100%, in actual blindness to it’s phenotypic effect, then it’s still entirely accidental.
I swear that something like this paper, i.e. on the subject of directed mutations causing malaria resistance (and probably Melamed et al. 2022), has been discussed either at Panda’s Thumb or somewhere else on the web in the not too distant past. But I can’t immediately summon the link.
I think I want to see this study repeated with a whole lot more than 11 individual donors (7 African and 4 European). The events of interest (20A->T in the HBB gene) were seen in three of seven African donors and none of the European samples (that’s how I read Table 1). That doesn’t seem to me to be very many individuals.
The one I remember was about how the malaria parasite evolves chloroquinone resistance thru a double mutation. Here is a link about that: Sandwalk: Taking the Behe challenge!
