In fact DNA intermediates with introns spliced can be reintegrated into the genome.
Further, faulty viruses can acquire oncogenes (intron-splicted, mtuated versions of growth factors, like EGF and HER2/neu) and transfer them to other cells via cDNA intermediates. It's not hard to believe that nature has in fact passed BRCA cDNAs around via retroviral intermediates.
RT doesn't work that way, it requires a specific site near its target gene in order to make the DNA strand. There is off-target activity, but it is almost certainly vanishingly rare.
anyway, if you're really so hung up on this, let's drop the viral intermediate and focus just on pseudogenes (instead of viral retropseudogenes), which are exactly the thing I described in my first comment.
so, if you want to demonstrate your claim, you would need to write a script that showed that there was no pseudogene that ever inserted at a nonspecific site. You can't show that. ergo, my proposal is more likely than yours. Further, it's support by evidence- for example, the genome is studded with p53 pseudogenes that reintegrated from cDNA nonspecifically.
Further, I'm not sure what the relationship of probabilities to the number of particles in the universe is. The probability of any given sequence emitted by hmmer as the "highest probability" is tiny (often 10e-50 or better, and for very good matches, 10e-138). So what's your point?
the work is mostly on okazaki fragments, but a major conclusion from my phd thesis was that B-RNA is stuck because of a very low probability event (the breaking of a large number of hbonds simultaneously).
Fine, then, a DNA-RNA base pair mismatch incurs approximately 1.5 kcal/mol penalty, which is a 1:10 less likelihood of matching. 3' UTRs of genes are what you need to reverse transcribe (by accident) the mRNA of interest to generate the cDNA you describe. On average they are around 700 bp, the odds of finding an exact match are about 700/4^18 - then a one bp mismatch is 700/4^17 times a 1:10 hit in terms of competitive binding. Two bp mismatch is 700/4^16 times 1:100. Then you have to consider that it's evolutionarily unlikely to have segments that exactly or inexactly match tRNAs because the resulting dsRNA is likely to engage in silencing via the DROSHA mechanism - probably because our bodies like to guess what - get rid of ssRNA viruses. So these numbers are probably at least on the order of 1:10 or even 1:100 or more in the wrong direction.
and yet, existence proofs demonstrate you are wrong. Again, re-read the section on virus tumor oncogenes in The Biology of Cancer; pretty much everythign we know about oncogenes came from this physical mechanism.
what? Most oncogene duplication comes from chromosomal abnormalities, or occasionally retrotransposon capture. Completely different mechanism from reverse transcriptase amplification. Occasionally retroviruses will incorporate themselves near or inside an oncogene and activate (and sometimes copy them) but again, that is not the same mechanism as nonspecific gene duplication, and will almost certainly not produce the same molecular product as a cDNA.
Remember, the patent is a MOLECULE patent, not a PROCESS patent.
Yes, and what I'm demonstrating is there is likely prior art in the form of cDNA molecules identical to the Myriad molecule that have existed in cells at some point in the past. That fact, which SCOTUS convenient ignored, is sufficient to override the idea that cDNA molecules can be patented.
Anyway, your comment about oncogenes again shows you haven't read Biology of Cancer. if you read the first four chapters, it works out the history through which we worked out the understand of oncogenes. And the history is different from what we know now to be the prevalent mechanisms. The use of tumor viruses, which is nicely explained, demonstrates that scientists had already described the phenomenon I'm cited in the mid-1970's. That phenomenon wasn't really followed up on after the mid-80s, when people got better mechanisms and a larger understanding of cancer. But if you go back to the tumor virus literature and really understand it at a fundamental level, you have to acknowledge that BRCA cDNAs identical to the Myriad patent have almost certainly existed in both free (nucleoplasm) and integrated forms in at least one cell in the past. Whether that cell survived, is irrelevant.
In fact DNA intermediates with introns spliced can be reintegrated into the genome.
Further, faulty viruses can acquire oncogenes (intron-splicted, mtuated versions of growth factors, like EGF and HER2/neu) and transfer them to other cells via cDNA intermediates. It's not hard to believe that nature has in fact passed BRCA cDNAs around via retroviral intermediates.