Thanks for the admission and it only makes my point stronger. It isn't about breakthrough in treating cholera, It didn't isolate and tell us the genes to target.It gives no workable data to finding a cure or treatment. Its more about using natural selection than anything else and it doesn't demonstrate any practical thing that would be lost without macroevolution theory because in the end we will still have to do the very same larger study not on chimpanzees but on modern humans to get the answer we need that I said from the start and you tried to handwave away from.
Despite your dismissiveness, the paper does find potentially important results, and do so based on the presence of natural selection. Here's the logical process, using quotations from the paper:
"We identified 305 candidate selected regions using the Composite of Multiple Signals (CMS) method."
"We previously developed the Composite of Multiple Signals (CMS) method to pinpoint regions of positive selection in the genome with more power and specificity than any single test(
23,
24). Here, we used CMS to identify targets of positive selection in a population from the Ganges River Delta, and then searched for association with cholera resistance among the identified targets."
"The CMS test combines three indicators of positive selection – long haplotypes, high-frequency derived alleles, and highly differentiated alleles – to identify narrow candidate regions." (That's where the need for knowing the derived allele comes in.)
"We looked for evidence of enrichment in the 305 selected regions in the BEB population using INRICH, a permutation-based genome-wide analysis tool "
"One gene set was significantly enriched in the BEB population - a module of genes in the expression neighborhood of
IKBKG. . .
IKBKG encodes the protein NEMO (IKK-γ), a subunit of the IκB kinase that activates canonical signaling of nuclear factor (NF)-κB." (There's a biological finding, based on the natural selection results.)
[The selection results were then confirmed with a small association study of the 305 regions.]
"To further investigate this, we evaluated the effect of cholera toxin on inflammasome activation in mouse macrophages
in vitro and found that it induced robust IL-1β secretion in LPS-primed mouse macrophages."
"We developed a model of the human innate immune signaling pathways that respond to
V. cholerae infection and have been selected in the BEB population (
fig. 5). In this model, inflammasome activation and the NF-kB signaling pathway play an integrated role in TLR4-mediated sensing of
V. cholerae."
"We found the most significant overlap of our selection and cholera association data near the novel gene
SNRNP200, which encodes a previously uncharacterized RNA splicing, ATP-dependent helicase shown to bind caspase-4(
50). The murine homolog of caspase-4, caspase-11, is a key regulator of caspase-1 activation in response to Gram negative bacteria, including
V. cholerae, and subsequent inflammasome activation(
47)."
"The NF-κB signaling pathway we identified as under selection in the BEB population modulates gut epithelial integrity and the interaction between the mucosal immune system and gut microflora(
58). . . We noted a significant overlap between genes that are highly selected in the BEB population and loci that are strongly associated ... with an increased risk of ulcerative colitis... Thus, pathways under selection in the BEB population, and potentially involved in susceptibility to mucosal infection with
V. cholerae, may also be relevant to understanding a common autoimmune disease occurring at the mucosal surface."
No, the paper does not tell you how to cure cholera. But it does provide an important piece of evidence that variation in the innate immune system, and specifically in the genes that activate the NF-kB pathway, affects how humans respond to cholera-causing bacteria. That's good for better understanding what makes cholera pathogenic, and might provide a clue for developing therapies. It also provides information about the function of a previously uncharacterized gene, and suggests a reason that south Asian populations have higher rates of inflammatory bowel disease than some other populations. These are all new pieces of information which contribute to the larger goal of understanding and improving human health.
In addition to everything else you must have no idea of what the word practical means. Its YOUR claim that is wrong. IF another wider and larger study focusing on modern humans has to be done to get a practical treatment for cholera than only in your dreams can you present this paper as a practical application that would be lost if we do not adhere to macroevolution.
But the larger, genome-wide study in humans of cholera is only going to happen because this preliminary study showed this was an area likely to yield results. Again, that's how real science works: you do a small study, find promising leads, and follow up with a larger study. And then more studies after that, and still more. If this stuff were easy, we'd already know the answers.
