Vitellogenin and Common Ancestry: understanding synteny

Hi Tim - vitellogenins are the main component of yolk in egg-laying organisms. They’re made by the mother, transported through the bloodstream, and are deposited as the egg yolk.

Placental “yolk” is made up of other proteins (not vitellogenins).

Thanks Dennis. By “placental yolk” do you mean the minuscule amounts of yolk present in the embryo or something else? Also, do you know what produces this? I’ve searched on my own and could never find it.

-Tim

Yes, the minuscule amounts of yolk. As far as I know, all we know about it is that it is not produced by VIT genes.

Thanks Dennis. But just playing through my head what a conversation with a creationist would look like, they’d say of course the mammalian “yolk” would not be produced by VIT genes, since we don’t see those genes in our genome anyway. But maybe by something with similarity to VIT genes, and then of course nominate what we call the VIT pseudogenes as a contender. Then we’re back to explaining this in more generic terms as to how pseudogenes don’t code for proteins and all that. But the uniqueness of “humans don’t need yolk” as a differentiator for this argument is lost. Unless we can one day find out what in fact does produce this mammalian “yolk.”

-Tim

Hi Tim,

Well, you could point out that there are no genes in the human genome with similarity to VIT genes. That and you could point out that the VIT pseudogenes are so far gone, that not even young-earth creationists try to argue that they are somehow providing the minute amount of “yolk” placentals have.

Thanks Dennis. I think that could be helpful but could you elaborate on those points? The creationist could say that the VIT pseudogenes are similar enough to the VIT genes to produce mammalian “yolk.” If I then said, no, they’re not similar, then they could ask how have we arrived at the conclusion that they’re VIT pseudogenes at all? In which case no matter what I say I’ll be pointing to some similarity and then come across as if I’m contradicting myself. At which point the creationist will just laugh and consider me discredited. As to saying not even young-earth creationists argue that these could produce mammalian yolk, I’ve run across this very argument on at least a couple creationist sites. I referenced one. So I couldn’t make that argument as if a creationist ran across the same content online I did then they would also consider me discredited for saying that no such argument is being made when in fact it has. So I guess it hinges then on whether or not these VIT psuedogenes are so far past the gone in comparison to other pseudogenes that you’re looking at a slam-dunk argument that they are not functional in yolk production. How can I best articulate this case? And is this so vastly different than other pseudogenes we’ve seen advanced as arguments for common descent that are shrugged away by creationists?

In any event, you’d think that a research study (Biologos funded or in your lab?) could settle this to the satisfaction of any creationist committed, at least in principle, to some measure of intellectual honesty. If you could remove the VIT pseudogenes from say a rat genome, and validate that embryos produced lacking this component develop normally, you would have demonstrated the uselessness of this fossilized genetic relic. With all the effort and funds already expended to convince creationists of the reality of common descent/evolution, you’d think this effort could be well justified. What do you think?

-Tim

im not sure dennis. what about this one?:

Hi Tim,

The VIT pseudogenes in humans are not capable of being expressed as yolk genes. In order for a gene to function, it has to have numerous sequences that do certain jobs: a promoter sequence that tells the cell to start transcribing mRNA at a certain spot; within the mRNA, there needs to be a translation start sequence; the mRNA itself results from splicing out introns using specific splicing sequences; and the portion of the mRNA that has the coding sequence needs to have an uninterrupted run of codons that are intact, without a “stop codon” that tells the ribosome that it should cease translation. The VIT gene fragments in humans are defective in all of these requirements (and more).

The reason why we can recognize them is that despite these defects, some fragmentary remains of their sequences persist. These sequences, though fragmentary, match up with functional VIT sequences seen in other species and sit within conserved blocks of synteny, as the original post describes. There can be sufficient similarity to recognize the remains of these genes without those sequences having what is needed to be a functional gene. In fact, VIT pseudogene sequences could be almost identical to functional VIT genes but still be defective, if mutations were present that prevented gene function.

So, though the argument may be out there, it is not being made by anyone with an understanding of how genes work. Tomkins himself does not take that tack, because he knowns that argument is flawed.

As for doing a study to remove these sequences from a mammal, the experiment has already been done, as it were. “Removing” a gene is often done by introducing the exact sort of mutations into it that we already see in placental VIT sequences. Fully deleting a gene is not necessary to remove its function.

Hi dcs,

That’s a case where one short region of a vertebrate gene has relatively weak similarity to a small portion of an insect vitellogenin. If you go far back enough, yes, that sequence likely shares a common ancestral sequence with vitellogenins - but it’s not “a vitellogenin” - it’s a small portion of mildly VIT-like sequence used in another gene for a non-egg-laying function.

This is a case of “useful protein domains” being mixed and matched over evolutionary time. So, yes, point taken - there is one vertebrate gene with one domain with weak but significant similarity to a small portion of an invertebrate VIT gene. My point, in the context of Tim’s question, is that there are no genes in the human genome that act as VIT genes in the vertebrate sense of supplying egg yolk.

Here’s the figure showing the ~25% identity for that small region:

Hello Dennis,

Just to point out the sloppiness of evolution, there are usually multiple translation start sequences; multiple splicing products, not all of which are functional; and of course an open reading frame is necessary, but a stop codon isn’t. Sometimes, read through is a feature, not a bug:

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Yep - viruses do even wackier stuff to compress more function into a tiny genome. We may well find similar examples in eukaryotes in the future.

This “looseness” allows for new stuff to crop up as well - new genes, new parts of genes…

Thank you Dennis. I think that helps a lot. I know there is a lot of skepticism generally amongst creationists that pseudogenes are not “functional,” but it seems the excessively degraded nature of these genes with their missing so many necessary components for effective translation adds to the effectiveness of this example.

Regarding the experiment I suggested, however, no matter what argument we advance and not matter how otherwise convincing it ought by every right be, creationists will still hold out hope that there is some other function this genetic sequence may serve. And if we knock down argument after argument of the various functions they might propose, they will still just assume that there is some as of yet unidentified function that maybe requires a level of understanding that we do not yet possess. And they would likely apply the same expectation as to why the sequence shares similarity and synteny with yolk-producing genes when it has nothing to do with yolk production. They would claim that if we knew enough about the mysterious inner workings of our genetics an answer would suggest itself. By removing the sequence entirely, you nullify even that hope.

Is this something that is practically achievable for a geneticist such as yourself or an organization with the connections and funds of Biologos? Thanks Dennis!

-Tim

Hi Tim,

While the experiment is straightforward, it is not likely it would be done. Experiments on animals need to pass an ethics panel, and that requires demonstrating that the proposed experiments will provide new information and not duplicate other work. So, one would have to make the case that deleting those sequences in a mammal would be worth the animals sacrificed in the process. Since the VIT sequences are obviously defective to anyone with cell biology / genetics knowledge, the proposed experiments would likely not pass a review panel for that reason. They would also cost several thousand dollars to perform (even excluding wages). So, it’s not likely you would find anyone willing to do the experiment, even if it somehow was green-lighted by a review panel. There would need to be some evidence for VIT function from those sequences, of which there is (obviously) not. As a Drosophila geneticist, this type of work is outside my skill set - but even if it were I would not propose doing it, since it would fail the ethics panel.

Thanks Dennis. I guess that’s the end of that dream then. Makes sense completely from an ethical perspective, I agree.

So I keep coming back then to how I would play this example out with, say, my creationist friends and family. And I could envision the following types of scenarios where they may suggest other “functions” for this pseudogene. Even given the expectation (hopefully) that I could categorically convince them as you’ve convinced me that there is no earthly way this thing could ever code for any protein, they could suggest that maybe there is something going on at a biochemical level, as the ENCODE project indicates that some kind of activity is going on across roughly 80% of our genetic code, most of which is non-coding, and that whatever that “something” is has some subtle but important biochemical function that chains/cascades down the road. Or they could suggest that this genetic sequence may do nothing more than maintain the structural shape of that section of the chromosome to better facilitate its function. They could suggest that maybe it serves as a site for epigenetic bonding. I mean, this is just pulling ideas straight out of thin air, and some or all of it may be completely ludicrous, but that is pretty much how many creationists operate anyway.

It is for this reason I find other types of genetic evidence more compelling. Such as relics of retroviruses that we see leave distinct “fingerprints” on our genome, some of which are still so intact we can reactivate them into spawning new viruses. That type of evidence doesn’t rely on demonstrating no function, just demonstrating that we can observe certain genetic activities happening today and discover unambiguous relics of those same types of events in our own genetic past, in ways clearly traceable for ancestry.

But I’d like to get your thoughts on that. Is demonstrating to a creationist the lack of function of a pseudogene anything we are likely to ever accomplish? Is there lower hanging fruit than this amongst the genetic evidence available to us? Thanks!

hey tim.

can you give a specific example? thanks.

Here you go!

-Tim

thanks tim. now, what about the posibility that those retroviruses “infacted” by human genome and not the opossite?

Well, that is where present day observation factors in. We observe retroviral insertions in real life. To then suggest the reverse to “explain away” the evidence would strike even many creationists (I hope) as just too obvious a case of special pleading.

-Tim

as far as i know we still not observe an erv but only an infaction that doesnt pass into the next generation (like hiv). so if we go by observation then we dont have evidence that this is a result of retro-viral infaction.