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Comment by JunkDNA | Hacker News Reader

I was on one of the teams that refuted the claims of horizontal gene transfer in the original human genome paper. The bar for establishing a true case of horizontal transfer in vertebrates is high. It’s really improbable given the required sequence of events laid out in the article. It’s one thing for some DNA to get picked up by random cells in the organism (happens with viral infection all the time). Getting to the germline cells and becoming inherited is a whole other story given that vertebrates have evolved mechanisms to guard against this specific scenario.

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When "vertebrates have evolved mechanisms to guard against this specific scenario", it hardly sounds "improbable."

well, not when the protection is against any form of DNA contamination and not specifically foreign DNA intrusion

the fact that random large mutations typically lead to an inviable zygote should be enough evolutionary pressure, it doesn't need to be specific protection against the entry of external DNA

The sequences we're discussing aren't really random, though. Presumably the chance of viability with such a sequence incorporated, though still low, is much higher than if it were a truly random sequence.

Are you sure?

Having one foreign sequence which have some specific features (to keep the originating organism viable) could have a chance of never being compatible with the target organism.

Having a completely random sequence by definition have some chance of being compatible.

The question is which scenario has a higher chance of success.

This is a case I could see going either way. Random mutations are probably much smaller and closer to the original, and therefore potentially more viable. Yes, it's random, but most of the time it won't have a major effect on the proteins the DNA generates. On the other hand, if we are talking about transferring segments, there's the potential of that DNA to create actively harmful proteins.

I just read the PLOS one paper. The arguments they brought forth were strong. If this had been my paper, I would have been livid if I had been rejected. However, given the fragmented and buggy state of bioinformatics tooling and databases at the time, I can easily imagine how their extraordinary claims did not the cross the "beyond reasonable doubt" threshold. From a reviewer's perspective, a couple matching disulfide bridges and a negative Southern alone might not have convinced me either. Glad it worked out for her in the end though.

The issue with the evidence in that paper is that they used primers to amplify the specific genes of interest. That introduces a strong assumption at the start of their analysis: specifically, that these genes appeared in the genomes by some HGT process instead of independently being duplicated internally in each genome from another gene shared among the species. Whole genome sequences were not available for these species at the time. A modern, more complete analysis would look into homologs across whole genomes and try to reject that hypothesis, which is much less extraordinary than animal germline HGT.

That's precisely why the authors published the new Cell paper https://www.cell.com/action/showPdf?pii=S0168-9525%2821%2900... with stronger evidence from whole genome sequence to support the HGT hypothesis. I'm still trying to wrap my head around Figure 2 there, so I'm on the fence.

The Trends in Genetics (not Cell) paper seems plausible. I don't study fish genetics or evolution. As I remember, fish genomes tend to have more genome-wide duplications and losses in comparison to other vertebrates. One possibility is that some fish lose AFPs because they don't need them – i.e. the observation could be caused by loss of function instead of gain of function due to HGT. I have to admit that the chance of gene losses across multiple fish lineages is pretty tiny but it is at least associated with a known mechanism.

Anyways, an interesting article.

My understanding is that inherited HGT in vertebrates is now an established mainstream position and that it was mainly the low quality of the original sequences that prevented people from refuting this point (specifically in humans). A lot of the stuff published in 2001 about human genomes was later shown to be of dubious quality, massively overstating the value of the data to make strong conclusions.

So did you know about the paper in question and if so how convinced are you of the claims/evidence in this specific case?

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