I haven’t read it. The critiques I’ve seen suggest that it’s not even close. My point was that he is right that “sufficiently novel” is a separate criterion from “technically correct.” There are journals that consider only the latter and not the former. What he seems to be missing is that even those journals would not publish a “technically correct” paper that shows, say, that walruses actually contain mRNA, tRNA, rRNA, miRNA, piRNA, and several other classes of RNA. There is still some kind of standard for what constitutes an actual scientific paper, and I have the sense that this paper couldn’t even meet that. It doesn’t seem that it’s worth my time to read. Do you disagree?
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Well thank you for reading this discussion. Since you’re an editor I respect your opinion. Of interest was the conclusion which it appears you concur. Thank you for linking to your earlier discussion where you said:
A straightforward frameshift, to a new protein sequence, is not the likely explanation. If that’s what Ann Gauger wrote, then she’s right.
You suggested more iterations would remove false positives. Why should more iterations add true positives in the case of PR.C when no credible hits are returned in the first pass?
You’re welcome. Ohno was wrong. This has no bearing whatsoever on evolution or on overprinting or on de novo gene birth. But he was wrong, and it is appropriate to make this known so that scientists do not cite the paper as an example of gene birth by frameshift. As I noted a long time ago on Biologos, I think Ohno was talking about overprinting. Nevertheless, it seems that he postulated a single nucleotide insertion that created a frameshift to yield a new ORF. That is a completely normal and reasonable mechanism, but the nylonase story seems not to be an example of that mechanism.
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???
In my reply above, I was implying that a lower e-value cut-off would reduce the numbers of false positives to the other queries. This was my gut reaction to the values in Fig. 1 that were, in my estimation, meaningless. That had nothing to do with recovering hits to PR.C.
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Thanks for the clarification.
This was my gut reaction to the values in Fig. 1 that were, in my estimation, meaningless. That had nothing to do with recovering hits to PR.C.
Ok, the better way for me to frame the argument is that the query that returned zero hits for PR.C was so relaxed than when the same relaxed parameters were used for NylB, thousands of hits (including spurious ones) appeared. This implies PR.C doesn’t exist in protein databases.
The loose end regarding nucleotides can be tied using BLASTN since Ohno gave a very specific sequence for something existing only 100 years ago. I recall doing it, but I just didn’t include it in the paper as I thought the protein searches were more compelling.
At this point the conclusion is not much in doubt, it’s the methods and materials. The extraneous parts can be simply deleted or pointed as outside the scope of the central question whether PR.C existed or not.
Thanks for you criticisms. They were immensely helpful.
Is this the PR.C DNA sequence you’re using? I just copied it from the PNAS paper but it might be wonky. I put a paragraph break where the inserted T (suggested by Ohno) would go.
T C G C C G A G C C A T G G G C T A C A T C G A T C T C T C C G C C C C C G T C G C G A T G A T C G T C A G C G G T G G C C T C T A C T A T C T C T T C A C C C G C C G C G C T A C A C C T T C G G A G A C A C T C G A
G A A C G C A C G T T C CA C G G C C A G C A C C C C G C C A G G T A T C CCGGAG C G C G G C C GGGGAGCCGACAC TCGACAGC TGGCAGGAGG CCCCGCACAACCGCTGGGCCTTC G C C C G C C T G G G G A G C T G C T G C C C A C G G C G G C G G T C T C C C G G C G C G A C C C G G C G ACGCCCG CGGAGC CCG TCG TGCGGC TCGACGCGC TCG CGACGCGGCTCCCCGAT C T C G A G C A G C G G C T C G A G G A G A C C T G C A C C G A C G C A T T C C T C G T G C T G C G C G G C TCCGAGG TCCTCG CCGAG TAC TACCGGGCGGG TTTC GCACCCGACGACCGTCAC CTGCTGATGAGCG TCTCGAAG TCGC TG TGCGG CACGGTCGTCGGCGCGCTGATC 'GACGAGGGGCGCATCGATCCCGCG CAGCCCGTCACCGAGTATGTACCCGAGCTC G CGG GC TC CGTC TACGAC GGGC C C TCCG TGC TGCAG GTG C TC GA CATGCAG AT C T C G A T C A C T A C A A C G A (G G A C T A C G T C G A T C C G G C C T C G G A G G T G C A G A C C C A C GATCGC TCCGC CGGC TGGC GC ACGCG GC GAGAC GGG GACCC C GC CGACACC TAC GAG TTC C TCAC CAC CC TC CG CGGCGAC GGCGGCACC GGCGAG TTCCAG TACTGC TCG GC GAACACCGACG TGCTCGCCTGGATCG TCGAG CG GG TCACCGGTCTG CG C T A C G T C G A A G C G C T C T C C A C G T A C C T G T G G G C G A A G C T C G A C G C C G A T C G G G A T GCGACCATCACGG TCGAC CAGAC CG GC TTCGGC TTCG CGAACGGGG GCG TCTC C TGCAC CGCGC GGGATC TCGCACG C G TGGGCCGCATGATG C TCGACGGCGGCG TC G C TCCCGGCGGACGGG TC G TATCG CAG GG C TGGG TG GAAAGCG TGC TG GC CGGC GGC TCCCGCGAAGCCATGACCGACGAGGG TTTCAC C TCCGCATTCCCCGAGG G C AGC TACACGCGCCAG TG GTGG TGCACGGGCAACGAGC GCGGCAACG TGAG C GG C ATCG GCATCCACGGC CAGAAC C TCTGGC TCGATCCGCGCACCGACTCGG TGATC GTCAAGCTCTCG TCGTGGC CCGATCCCGACAC CCGG CACTGGCACGGGC TG CAG AGCGGGA TCCTGC TCGACGTCAGC CG TG CCC TCGAC GCG G TG TAGGCGGC TGA
Hi Steve,
Yes that was the paper. My construction method was to take the original Okada sequence and painstakingly compare it to what Ohno typed in.
You correctly note the Ohno deleted the “T” to make PR.C and then when “T” was inserted into PR.C it made NylB, because “ATG” codes for methionine.
Toward the end there is an inadvertent stop codon that Ohno didn’t mention! I suspect he omitted mentioning it, but in the worst case it was a typo. I’d like to be charitable and say it was just an omission he didn’t mention.
I thought it should be a rather simple search to do, and it didn’t take but an hour for the first evaluation.
The larger question, which was much harder to answer was, “did other nylonases exist prior to 1935?” That was the hard part of the paper. It took a long time to establish mammalian trypsin is a nylonase, for example. The other hard question was whether there were other NylB’s prior to 1935. We included that in our paper because it showed that enzymes in the past might be able to degrade man-made compounds.
The nucleotide search was rather trivial. Thanks for posting.
It’s obvious that Ohno’s hypothesis is wrong. Nylonase B didn’t arise from a frame shift, unless the frame shift was the origin of the entire protein family, only one of which is nylonase B. It’s also obvious that nylonase B didn’t split from nylonase B’ in 1935 but much earlier. But it isn’t clear that nylonase B didn’t evolve its increased nylonase activity after 1935. The first two bits are what I have previously agreed are correct.
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From our paper:
We conclude that all of these nylonases and their close homologs existed prior to 1935, although in some cases there may have been adaptive modifications after 1935.
The reason we used the word “may” is the fact mammalian trypsin had nylonase activity. We referenced that the 2-residue change in Kato’s experiment points to the likely adaptation, if any.
It seems more than one scholar here would agree with these statements, and they were established before your study.
It also seems that there are a large list of unresolved concerns about the technical validity of your study.
It appears that there are some points of agreement, and some points of disagreement. I’m not sure what reasons the editors gave you for rejecting the paper, but it does not yet seem suitable for publication to us. Perhaps some concerns could be addressed, but we are not yet clear what this analysis adds to the literature.
Of note, your YEC beliefs have absolutely nothing to do with this assessment. @stcordova, I hope you appreciate our effort to consider your paper carefully.
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Sincere thanks to everyone here for taking time to read and comment.
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When you do good work, my public position will be to acknowledge that it is good work, and to hold that it should be published in secular journals. I would hold you to the same standards I hold other scientists, and the same standard I hold my students. It is a very high standard.
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At this point, I am interested in writing a paper you and others deem technically sound. There are other venues to release our work than a journal, but correctness and integrity take priority.
I respect if an editor doesn’t think our work is novel, but if we are rejected for that reason, but still have a solid paper, then there are other ways to communicate it than a journal, and we can do so with confidence we are speaking truth and what we say is unassailable.
The first and most important concern was whether the final conclusion was right. No point writing it if the conclusion is false.
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As we explained, you seem to have overstated your conclusions.
I suggest you write some text explaining the common agreement and common ground you found some of the posters here. For example:
If you can put together an explanation of the situation, without creating the false impression that these scholars agree with you on more than this, that would be a win for you. I suggest you write that up, using quotes (but NOT quote mines), and carefully explaining where they diverge from you:
And other points of salient disagreement, of course, would be important to keep clear.
If you could write such an explanation, and have them agree that you correctly represented them, it seems like this could be a win for you. Part of your concern is that scientists in the origins conversation present Nylonase as evidence when it really isn’t evidence for what they say it is. If you had an approved explanation, such as what I am suggesting, it would give you some standing to press back on this.
So that is what I suggest.
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FWIW,
I just did a BLASTN of the sequence Steve lifted from the paper and got only 6 hits under default parameters, and PR.C is absent. I think some of the cut an paste off a PDF of Ohno’s paper lost a few characters. I’ll have to look in my archives for the clean sequence that was painfully reconstructed from the published paper.
I recall now that PR.C looked suspiciously absent, but I thought, “it can’t be this easy to refute?” This after all was a widely cited paper, if not in literature, in the popular press (by Dennis Venema and Ken Miller).
As I noted, the interesting question that the existence of nylonases raised and which we felt was important to address was whether a biological enzyme that existed prior to the invention of nylon could actually degrade nylon with few or no changes. That was the harder part of the study to establish.
ADDENDUM: I now recall, and it’s been a while since 2017 when most of the paper was written, that the absence of PR.C in the database could also mean that the sequence just didn’t enter the database! After all, we have only a tiny fraction of all bacterial sequences. So, like trying to disprove the existence of chocolate cakes orbiting Neptune, it was thus hard to say PR.C didn’t exist. We could only show it didn’t exist in the database.
It seemed rather compelling that bacteria digested a man-made chemical that never existed before 1935. Something as radical as a frame shift in Ohno’s time seemed like the appropriate level of change needed to create the requisite enzyme.
Finding things like mammalian Trypsin and plant Papain that could degrade nylon, at least made the case that a nylonase didn’t have to evolve after nylon was invented. Hence, at least the perceived need of a radical change was shown as incorrect.
Further, finding homologs of NylB would suggest NylB existed before 1935, and therefore the most parsimonious explanation for the NylB sequence after 1935 was not a frame shift after 1935 but that NylB existed in much of its present form prior to 1935. This was the case that was challenging to make.
It is worth mentioning, but it wasn’t in the paper, a nylonase is a necessary but not sufficient condition for bacteria to digest nylon and live purely off of nylon since the nylonase only made nylon-6 monomers from nylon-6 polymers. Nylonase alone didn’t provide the full metabolic pathway for the monomers to be digested. There had to be a capacity for the bacteria to digest nylon-6 monomers , and to my knowledge, that metabolic pathway has never been characterized. Hence, even if many bacteria have nylonases, they may not necessarily be able to digest nylons.