Go and look

I have said this before, but since fetal cells can linger in mothers for a long time, while maternal cells can be transmitted to offspring, there is a niche for a kind of cell that is transmitted indefinitely through the female line, and that would almost certainly have beneficial effects, at least on females.  This might show up as a growing mtdna haplotype.

It’s a niche, and niches end up inhabited – like the cell line infections in marine filter feeders, which phenom was predicted well in advance of detection.

If you found something like this it would make your career.  Especially if it were found in humans.

 

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29 Responses to Go and look

  1. Eman says:

    Nice idea, but it doesn’t apply to humans.

    • gcochran9 says:

      You’ve looked?

      • 415 reasons says:

        Such a cell would

        A) hit the Hayflick limit for cell divisions and crash because its telomeres would be exhausted and

        B) even if there were some way around this (immortalization) you’d wind up with so many somatic mutations accumulating that would never be fixed by sexual reproduction that you’d certainly get a transformed cell.

        If these cells existed they would exist in large numbers because eventually they’d turn into a cancer. Your point about the filter feeders is apt.

        • Jacob says:

          A) Didn’t happen to known transmissible cancers; doesn’t happen to stem cells; doesn’t happen to unicellular protists, so there’s no reason to insist that eukaryotic cells cannot or will not turn immortal.

          B) Human genomes are far more resistant to mutations than bacteria are, yet bacteria get by fine. Transformed cells would see three outcomes: they die, and the colony marches on. The new mutation is favored, and evolution happens as it does. Or they turn to cancer, proliferate, and kill the host.

          Turning cancerous would actually be favorable to these things over the short term, assuming they could get away with it. It would reduce odds of transmission, but evolution can’t account for future possibilities like that so it would happen anyway.

          So, that hypothetical mtDNA haplogroup Dr. Cochran referenced might see higher cancer risk, especially in infants & fetuses.

          • albatross says:

            I don’t think stem cells are a counterexample–they only have to keep going without turning into cancer for one human lifetime, whereas this transmissible cell line needs to keep going forever.

            Maybe one way this could work is if the cell line got into a state where it was evading being rejected by the host, but where most mutations that had any noticeable effect tended to just get it rejected.

            Changing into cancer also stops its transmission (kills its host), unless it always does so in a way that the new host adapts to immunologically in time to stop.

            The evolution here might be at the level of the line passed to a given host (if you evolve into cancer, then you don’t make it to the next generation; if you evolve into something that elicits an immune response, you get removed from this host and don’t make it to the next generation), but it might also be a competition among cells in the cell line–maybe if you get mutated and elicit an immune response, I survive while you’re removed.

            If the main driver of selection is the second one, then you could imagine this kind of cell line getting really good at evading immune responses. (But if it gets too good, then it may no longer face pressure to avoid turning into cancer within a single host.)

  2. Phille says:

    So you’d have to sequence placental water or possibly the placenta itself and look for something human-like but different from the rest?
    There is at least a ton of transcriptome data of the placenta. Given that these cells would also express some of their divergent genes, that might be good enough. But you’d probably need incredible sequencing depth to catch a couple of these cells.

  3. ecgwine says:

    I thought this was how we receive our gut flora? This would certainly fit the description of “cells transmitted indefinitely through the female line, and almost certainly has beneficial effects” but it’s hardly a novel discovery.

  4. Martin L. says:

    What if we have found them? Teratomas.

  5. caethan says:

    Thinking about how to look for such a thing. Let’s suppose for now that what we’re looking for is human-derived, which certainly makes things harder.

    I think my first pass would be to try and find some of those transmitted fetal cell lines, see what transformations they’ve had that might give us a handle on what to look for elsewhere. So take someone like my aunt who’s had 10 kids, sequence mom and dad from blood draws, look for mosaic variants in mom that match one of dad’s haplotypes. We’re getting some singlecell sequencing availability online, so once you find someone carrying a fetal line, run it through that, try and pull out the population of transferred cells. Then do bulk variant calling on that population, looking for major CNVs or mutations that are unique to the cell line. Do that on a bunch of families, get an idea of what a cell needs in order to establish it as a transmissible cell line.

    Then you need to go collect the blood of some virgin girls. Certainly adds some panache to the research. But you get a population that’s certainly never had direct fetal transfer of cell lines. Do your blood draws, look for mosaic variants matching your ideas about what a transmissible cell line might look like. If you find ’em, run a sample through single-cell sequencing to identify the population. Do the same thing for the kid’s mother and look for the same population there. Do sibs too, see how many of the sibs have them. Do dad while you’re at it. If only some of the sibs have it, once you’ve got enough families, you could even start figuring out what the hell the cell lines are doing!

  6. Rich Rostrom says:

    I see where the mother-to-fetus transmission could create a sort of maternal line. Fetus-to-mother, though… Fetus-to-mother-to another fetus? If the second fetus has a different father, the transferred cells could have wholly unrelated DNA.

    Also, it would provide for transmission (at this trace level) of mother’s alleles that were not included in the ovum – traits in fact, since it is whole cells that get passed on.

    If (big if) these cell lines can really persist and propagate, there could be all sorts of mysterious lineages. A woman has children by two fathers; her third child could have traces of both of the other men. But at trace levels, one would think.

    The other big question is to what extent traits of the passed-on cells are expressed. For there to be any expression, I would think that the cells have to propagate in the recipient. What kinds of cells can be passed? I would guess that only a limited number of types can pass, which constrains the traits that could be expressed.

    • albatross says:

      They’d still be at least half-siblings. But you’d think most of them would get zapped by the host’s immune system–rejected the same way you’d almost certainly reject your mother’s or sister’s kidney if it were put into you without taking drugs to prevent rejection.

      • mapman says:

        Immune system needs time to develop in order to start recognizing foreign antigens. Almost everything am embryo sees in first 3/4 of gestation period will be treated as its own.

      • Rich Rostrom says:

        The two children would be half siblings, but the second child could have trace cells from the first child, which would carry the DNA of that child’s father, who would be wholly unrelated to the second child.

  7. dux.ie says:

    https://www.cell.com/cell/pdf/S0092-8674(15)00843-0.pdf

    Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells (Mouse)
    Exposure to maternal tissue during in utero development imprints tolerance to immunologically foreign non-inherited maternal antigens (NIMA) that persists into adulthood. The biological advantage of this tolerance, conserved across mammalian species, remains unclear. Here, we show maternal (mouse) cells that establish microchimerism in female offspring during development promote systemic accumulation of immune suppressive regulatory T cells … selectively enhances reproductive success in second-generation females carrying embryos with overlapping paternally inherited antigens. These findings demonstrate that genetic fitness, canonically thought to be restricted to Mendelian inheritance, is enhanced in female placental mammals through vertically transferred maternal cells that promote conservation of NIMA and enforce cross-generational reproductive benefits.

    https://www.fredhutch.org/en/news/spotlight/2017/05/crd_harrington_jinfectdis.html

    Further analysis of P. falciparum in the (human) offspring to understand the role of maternal cells revealed that MMc positive infants were more at risk for malaria infection, but less likely to be sick or hospitalized when infected. This suggests that maternal cells may protect from disease development. … Dr. Harrington explained, “we think the babies may have acquired a graft of malaria-specific regulatory maternal cells which allow experience of infection but protection from disease. We know that in healthy pregnancies, maternal cells are enriched among antigen experienced T cells. In addition, during malaria, regulatory cells (classical Tregs, Tr1 cells) may protect from immune-mediated pathology. We hypothesize that these maternal cells influence or educate the fetal immune system in utero, or alternatively, they become directly activated during malaria infection in the infant”.

    https://www.ncbi.nlm.nih.gov/pubmed/10393697/

    <

    blockquote>Microchimerism of maternal origin persists into (human) adult life. (range: 9-49 years)

    • teageegeepea says:

      Evidently there’s a new journal of medical hypotheses (“Hypotheses in the Life Sciences”) to replace the old one and it has a paper on microchimerism which might be of interest to Greg:
      Dual-gender macrochimeric tissue discordance is predicted to be a significant cause of human homosexuality and transgenderism

    • Jacob says:

      “genetic fitness, canonically thought to be restricted to Mendelian inheritance, is enhanced in female placental mammals through vertically transferred maternal cells that promote conservation of NIMA and enforce cross-generational reproductive benefits.”

      Let me guess- the immune system learns not to attack 1.5 times the ordinary pool of human antigens it would otherwise learn not to attack, and thus is less likely to target its own offspring later on?

      That’s wild.

    • Horhe says:

      “selectively enhances reproductive success in second-generation females carrying embryos with overlapping paternally inherited antigens.”

      Is this an argument against interracial mating?

      There was a post here some time ago on hybrid vigor and weakness, with someone posting a paper on Icelanders that posits the ideal relation between parents for viability of fetus as being 4th degree cousins. Would this microchimerism be a further argument?

  8. Why wouldn’t it be killed by immune system?

  9. j says:

    I did not go and did not looked, but you seem to be talking about microchimerism, that is,the presence of a small number of cells that are genetically distinct from those of the host individual. WIKI: “Most people are born with a few cells genetically identical to their mothers’ and the proportion of these cells goes down in healthy individuals as they get older. People who retain higher numbers of cells genetically identical to their mothers’ have been observed to have higher rates of some autoimmune diseases.” I would speculate that cooperative organisms of billions of cells, like us, are workable when all the cells carry the same genes. In contrary case you have in-body competition i.e. the body fighting itself. A house divided cannot stand.

  10. crew says:

    This paper is creating waves in certain circles. Some think it means that all mammalian species are only 200,000 years old at most.

    http://www.pontecorboli.com/digital/he_archive_articles/he122018/1_Stockle_Thaler.pdf

    • Cloveoil says:

      I’m still curious why mtDNA trees sometimes don’t line up with total molecular evidence – at all. This is obviously true as regards placental mammals and birds.

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