Following up a bit more on this subject:
From @Agauger’s ENV Piece -
“In the years since that paper was published, many cases of beneficial loss-of-function mutations have come to light. With the acceleration of genome sequencing more and more evidence has been accumulating. In 2014, a review article appeared in a special volume of Genomics devoted to experimental evolution. It outlined what could be learned from the many genomic studies to date. Gregory Lang and Michael Desai described many “adaptive mutations,” meaning mutations that helped the organism or cell grow faster or reproduce more. One could also call these beneficial mutations, and they did. They noted this:
Most long-term evolution experiments thus far have been performed in bacteria or haploid yeast populations, where, in most environments, there exist a number of loss-of-function mutations that provide a selective advantage. Given the large target size for these types of mutations, loss-of-function mutations often predominate the spectra of mutations recovered from long-term evolution experiments. Some of these loss events are neutral, attributable to mutation accumulation in the absence of selection for function, such as the reduction of catabolic breadth in E. coli[17], [18], [43]. However, many loss-of-function mutations have been confirmed to provide a selective advantage. For instance sterility in yeast provides a selective advantage by eliminating unnecessary gene expression [41]. The availability of beneficial loss-of-function mutations and the large target size for these events ensure that these mutations will come to dominate experimental evolution over short time scales. Over long time scales or in specialized conditions, mutational spectra may shift towards gain of function mutations. In diploid populations, we may also see a shift in the mutational spectrum away from loss-of-function mutations, towards dominant or overdominant mutations [24], [54]. However, there is currently only limited data describing the mutations that occur during experimental evolution in diploids, leaving the exact nature of this shift unclear . [Emphasis added.]
The following paragraph that @Agauger omitted is of interest as well:
Mutations affecting gene dosage are common in experimental evolution, in particular under nutrient limitation. For example, in chemostat cultures, where growth is strongly limited by a single nutri- ent, mutations that increase the import of the limiting nutrient are favored. Evolution in sulfur-limited media leads to the specific amplification of the high-affinity sulfur transporter, SUL1 [27]. Evolution under glucose limitation selects for amplification of the hexose trans- porters [11,20,32], and nitrogen limitation selects for amplification of nitrogen transporters PUT4, DUR3, and DAL4 [31]. The fitness effects of these amplification events are on the order of 10%, roughly an order of magnitude more advantageous than the beneficial mutations observed in rich medium conditions. This existence of these large effect mutations, combined with the large population sizes, may partially explain why some of the smaller effect mutations observed in rich medium conditions are not found in chemostat evolution experiments.
What this mechanism - altering gene dosage – brings to mind is the greater issue of regulatory evolution. This greater issue includes subjects such as alteration of transcription factors and their networks, and also of small RNA-mediated regulatory networks. (Incidentally, CRISPR is a subset of small RNA regulatory mechanisms.) I would argue that, if one is going to be making sweeping claims about evolutionary trends that affect adaptation and morphological evolution (such as proposing “the First Rule of Adaptive Evolution”), regulatory evolution really cannot be ignored or pushed aside. Neither paper @Agauger cites in the ENV piece, nor Behe’s 2010 paper, mention these sorts of mechanisms.
All of which leads to a question for the privileged few (@NLENTS, @swamidass, @Agauger, @pnelson) who have access to Behe’s new book – in his book, does Behe discuss subjects such as the evolution of transcription networks, or microRNA regulation? If so, how does he classify the changes attendant with rewiring of the relevant networks? Gain, modification, or loss of function? (This question repeats, in a sense, the one I asked @Agauger above about CRISPR.)
Finally, in the ENV piece, @Agauger also takes a swipe at @swamidass :
“Note: Cancer is not a good model for asking this question in eukaryotes, because the gain-of-function mutations in cancer do not produce structures or traits that lead to anything beneficial for the organism.”
I don’t buy this for a second. @swamidass?