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An Outside Perspective

Since I mentioned retrotransposons and accumulated retroviral genomic litter in yesterday’s post, I’ll get a bit philosophical about that today. I’ve had a couple of interactions with people who read about all this and didn’t realize what state our genomes are in, and they were struck by all this. As they should be! It really is weird that we are all carrying around eroded bits of DNA sequences that got inserted into our genome from back before we were even human beings. And it’s similarly weird to realize that in many cases we’ve adapted to those sequences and found a use for them as spacers and scaffolding.

But that’s what goes on down there. Accidents happen constantly. Most of them are silent, and most of the rest are harmful to a slight or serious degree, but the ones that actually turn out to be useful get their chance. Did you up and duplicate a whole gene, so that now you have two copies of it? Well, OK, run with it. Maybe having double the expression is a good thing, or maybe it’s good to have backup expression if something goes wonky with one copy. Over time, both copies will pick up mutations of their own, though. Most things do. But maybe one of those will turn out to be useful in a different way. Congratulations! You now have a new receptor subtype or protein isoform, off doing its own thing. As I’ve said here before, evolution’s motto is “Hey man, whatever works”.

And the definition of “works” in this context is easy to state: did you live long enough to pass on your genes to the next generation? Did something make you a tiny bit more likely to be able to do that? That’s all you need. Those questions are tied in with the environment around you, of course. If something has changed – a food source has vacated the area, or the climate is shifting (heat, cold, rain, drought), or a new parasite or predator has moved in – then previously underappreciated mutations might come in handy. At the same time, some of your hard-won gains in another direction might suddenly be a burden. The deck gets shuffled all the time, lightly or thoroughly (perhaps there’s been an asteroid strike?)

What needs to be emphasized is that outside of living creatures, we have no good analogies to this. The closest thing might be the actions of geologic time and processes on the landscape, producing weird and various rock formations and terrains. Who could have ever predicted a limestone cave and its formations from first principles, or the striations and colors of the American Southwest or Australia’s? Outside of geology, if someone told you about planets and atmospheres and water vapor, could you have predicted the varieties of clouds, from billowing cumulus through thunderheads to cirrus horsetails, and the constant interplay of light and color among them? Could you have built up the idea, the picture of a blazing end-of-the-world sunset from just thinking it through? But even those don’t have the reproductive fitness aspect; they don’t have that thumb on the scale. We’re more startling than sunsets and crazier than caves. Living systems build complexity in a way that nothing else does, and they do it in a way that utterly foreign to our rational tool-building minds.

So we take them for granted. Maybe it’s because there are no examples of this at all until we look at living things, and then we see so many examples that we don’t know what we’re looking at any more. Zero evolutionary weirdness, or nothing but – it’s no wonder our perceptions are off. We’re surrounded by moving, energy-shifting self-directed hunks of insanely complex nanotechnology, performing functions we don’t completely understand in ways we don’t completely understand. I’m talking about your cat, or your houseplant in the window. We ourselves are more of the same: a pile of ridiculously complicated interlocking systems that we absolutely don’t really understand, and the only reason that we can use the word “understand” (or any words at all) is because of even more insane emergent phenomena called “consciousness”, “intelligence”, and “language”. We wouldn’t believe that such creatures, such constructs, such staggering lurching heaps of molecular machinery were even possible if we weren’t ones ourselves. But since we are, we just don’t think about it much.

40 comments on “An Outside Perspective”

  1. I wonder if the mindset behind the anti-vax and anti-GMO movements, while seeming at the surface to be more part of the political left, are actually a kind of hangover of young earth creationism. In other words, do most people have a kind of wrongheaded belief that we were engineered to be perfect by a master programmer, and we better not mess with the source code. In reality, we have one of those working legacy systems that’s a complete headache when you try to understand how it works.

    1. metaphysician says:

      I wouldn’t attribute it to any one end of the political spectrum. It fits as much with a Rousseau-ian view of the perfect natural state of man. The naturalistic fallacy finds many homes, and probably is as old as human civilization.

    2. Eric says:

      I don’t know why you associate anti-vax or anti-GMO with left-wing politics. Given how many trump supporters are refusing a COVID vaccine I would see anti-vax to be an extreme right-wing position. And in Europe at least, it seems to me that anti-GMO sentiment stems from a fairly conservative point of view- we don’t really know the consequences of shifting specific genes from one species or kingdom to another, so why take the risk.

      1. achemist says:

        This might be a country specific phenomenom.

        But both anti-vax and anti GMO is strong in e.g. the green party in my country. Lots of people feeling that this is “unnatural” and “full of chemicals that cannot be good”.

        This might be a rather conservative standpoint, but a lot of people from the left adhere to it

        1. johnnyboy says:

          I’m guessing here, but I think if you polled anti-vaxxers on their political beliefs globally, you’d get a pretty even spread of right to left leaning politics, with plenty of people calling themselves ‘independent’ who don’t trust any particular political system. I think a more clear association would be with people who distrust experts/authorities of any sort, which in some countries might be more the granola-lefty sort, and in others would be more the Qanon types.

    3. Carl says:

      Anti-vax took off with the whole Dr Wakefield thing, it was around before but it was so far out on the niche fringe it wasn’t relevant. Then he faked up a paper a bunch of news types and celebrities and other influence sorts jumped on it and took up the cause before anyone realised the paper was fake.

      How it went from that to the anti-authority stance it has now i’m not honestly sure. If i had to guess a lot of the influencer types probably got into it second or third hand from other influencers that where directly influenced by the paper. So there was no pro-authority bias in their support and when the countervailing push back came from experts after the fraud was discovered they struck to their guns because they trusted their source more than a random expert. And thats just basic human social dynamics at work, you interact with someone or their works a lot and you feel like you know them so you trust them more than someone you don’t.

      But thats just me making loosely educated guesses on why it stuck around after the fraud was discovered.

  2. osmarks says:

    Evolutionary algorithms aren’t really unique to biology now. They get used to design things like antennas, and in some experiments circuits on FPGAs (reprogrammable logic gate systems). The results have generally been pretty weird and hard to understand for humans, and the FPGA ones exploited quirks of the particular model and even individual device they ran on (often if simulations are used, the result will just exploit bugs in that, if it’s easier than a “proper” solution).

    1. metaphysician says:

      Being fair, we would probably exploit “bugs in the system” too, if we found any. One might even argue that we already do, if you want to consider the statistical indeterminacy of quantum mechanics to be a bug, in the “we don’t need to model this precisely, an approximation will do” sense.

    2. cthulhu says:

      About 15 years ago, I worked with the person who invented evolutionary algorithms for optimization. I learned a lot, very cool stuff.

      1. LdaQuirm says:

        *The* person?

  3. Sue says:

    One of your most beautiful, poetic pieces. Thanks!

    1. Amedeo Vetere says:

      Agree!!

  4. Ole says:

    I have definitely worked with some software code bases that were developed and functioned more according to these principles than not!

    1. No clue says:

      I think I might have written some of them 😀

  5. cynical1 says:

    Derek – Your blog is one of the bright spots in this life. Great science and the occasional philosophical piece that I can actually relate to and enjoy reading (like this post). Many thanks from myself and many others, I’m sure.

  6. Jonathan B says:

    Thank you for directing our thoughts back to fundamental philosophical questions. It is one of the privileges of a scientific education to see those big questions implicit in the genome.

    Our human tendency is to assume the best solution is the most efficient – and it may be for viruses – but in a complex organism how can we assess the selection advantage over millions of years of evolution of having “spare” DNA sequences that might eventually be utilised to generate an advantageous gene versus the cost of the ATP molecules hydrolysed to maintain those sequences at every cell division?

    It would appear that nature has done the calculation we can’t, and the benefit has indeed outweighed the cost.

    1. DH says:

      Evolution proceeds by local, not global, optimization. So even if there are more optimal genomes out there from a survival perspective, unless there are relatively “low energy” paths to reach them, we never will.

      1. Nesprin says:

        That’s not quite right- traditional optimization is very much a local search endeavor, whereas random mating and mutation can induce some dramatic jumps in the search domain, which can be terribly ineffecient and occasionally wonderful.

        Genetic algorithms attempt to recapitulate the random reassessment of the search domain seen in natural selection- it’s a valuable thing to shake out of a local minimum to go looking for the global one.

        1. James Millar says:

          Random mutation does have a pretty tough hill climb to get out of local, really. I think the classic example would be the optic nerve structure – no one would design it that way, but it would take an impossibly large number of simultaneous mutations to “redo” it without running into a low-fitness “blind crest” in the middle.

  7. Kar N says:

    Love to carry on – expelled from the Garden of Eden – with all my imperfections. Thank you, Derek and every brilliant mind above, for help live another day, thinking.

  8. E Ray says:

    Life is so incredibly complex that even with our supercomputers and vast understanding of biology, chemistry and physics when we try to cure our ills we look to see where nature has already done it before, instead of trying to engineer a solution from scratch: We find plant alkaloids that fit perfectly into a receptor; we find genes that underlie disease or confer protection; we discover organisms that can live in the harshest environments. Who would have predicted how the discovery of a thermophile would eventually lead to imprisonment of murderers AND fast and accurate diagnosis of a novel virus?

    1. Jim Hartley says:

      It’s remarkable how the most important tools in biology come from bacteria and viruses.

  9. Paul Brookes says:

    Another great example of excess baggage – the nuclear genome is littered with fragments of mitochondrial genes, presumably from failed attempts during evolution to migrate those genes from mtDNA to nDNA. It can be a real PITA when trying to quantify mtDNA by PCR – need to select primers very carefully so as to avoid accidentally amplifying from the wrong genome.

  10. APAJ says:

    A meandering river comes to mind as a distant but similar ‘inefficient, but it works’ analogue. Eons of accumulating debris and eroding the opposite bank slowly creating the most inefficient way of getting water from A to B, but hey, it’s getting there innit?

    Great piece! I’m off to do some more energy-shifting before the day is over.

  11. steve says:

    My college professor in genetics always talked about how man MIGHT have designed DNA from first principles but what never would have occurred to him (or her) would be to make it imperfect and subject to mutation. Incorporating random chance into design was always the discriminator between natural and man-made until recent times when we finally learned the lesson.

  12. exGlaxoid says:

    If you want an analogy to our DNA, just look at the US federal law (including the tax code, and most states laws as well).

    It was started 200+ years ago, and has been added to, changed, invalidated (by courts), held up and modified (by courts), and editted by politicians for 200+ years. If you ever try to read it, you will find a mess that is very hard to understand, much of it is now obsolete (laws regarding horse and buggy’s, slavery, and Prohibition come to mind), some of it contradicts itself (DOT and OSHA can’t agree if acetic acid is flammable or not), and much of it is useless or obscure. And some was inserted by lobbyists (aka pathogens) in the middle of the night.

    As a person who has tried to deal with many three letter agencies and has one say we must do X, when another says you must do Y, and a third says only Z will do, I think they are similar to our DNAs excess baggage in many ways.

    1. hopeful says:

      Or look at the Common Law that preceded it. Our whole system of juris prudence and the reality of Liberty were a happy accident born out of competing interests, none of whom had any interest in the Liberty we enjoy today.

  13. theasdgamer says:

    Do you know why comedians never tell vaccine jokes to anti-vaxxers?

    They won’t get it.

    1. sgcox says:

      Good one 🙂

  14. Todd Knarr says:

    It’s some of the same misconception that Scarne tries to dispell in Scarne on Cards. And he’s absolutely right, you really do need to discard misconceptions about probability if you want to win at gambling or understand how our DNA evolved since they’re both dealing with large numbers of random events. The primary statement is “The odds on being dealt a royal flush don’t tell you it’ll never happen. They tell you _how often_ it’ll happen.”. Every individual is a new round dealt _and_ a new dealer added to the pool, and we’ve been playing since at least the first single-celled organism emerged. It shouldn’t surprise anyone how many weird and improbable hands have cropped up along the way.

  15. Daen de Leon says:

    You write in a way that I haven’t come across since Stephen Jay Gould (although I suspect you may part company on some issues).

    On the subject of repurposing those retroviral inserts, one of the things that stunned me in my own area of non-invasive prenatal genetic testing was finding out that Syncytin-1, the protein which essentially makes placentas work, is a repurposed human endogenous retroviral element that likely became part of our genome 63 million years ago.

    It’s … just mindblowing.

  16. heteromeles says:

    If you want a layperson’s guide to a really useful theory (mosaic theory of coevolution) on which to hang evolution, check out John N. Thompson’s book Relentless Evolution.

    On a different subject, a recent article in Quanta (https://www.quantamagazine.org/scientists-catch-jumping-genes-rewiring-genomes-20210512/) goes on about researchers wondering if transposons get evolutionarily recycled as gene regulators. That’s another fun idea to think about.

  17. mark says:

    Derek,

    Given all of this vast complexity for even simple life…. and your love of space is something looking back at us in the night sky?

  18. Tom says:

    A huge part of ‘evolutionary effort’ seems to be directed towards protecting against a diverse array of rare but catastrophic events. Off the top of my head humans (and many other species) have mechanisms for dealing with:
    Heat (sweating, shade seeking)
    Cold (shivering, burrowing, restricting bloodflow to extremities)
    Famine (Hunger response, fat storage, catabolism)
    Rotten food (sense of smell, disgust reflex, vomiting)
    Heights (vertigo, lowering centre of mass)
    External parasites (itchiness, grooming behaviour)
    Viruses and bacteria (Immune system)
    Embedded foreign bodies (Immune system, pus)
    Wounds (Sense of pain, blood clotting, scabs, broken bone healing)
    Poisonous insects (intrinsic fear of anything with the Wrong Number of Legs)
    Animal attack (screaming, fight or flight response, shielding face with arms)
    Asphyxiation (increased breathing with elevated CO2)
    Overexertion (tiredness)
    Social ostracism (social anxiety, shame)*

    * Unsubstantiated personal opinion

    Every one of these responses likely came to be because of untold thousands of instances of our ancestors surviving over their kin where these challenges to survival became severe enough.

    Furthermore, life seems to have evolved in such a way as to guard against unknowable future challenges. This is primarily through diversification, and is why gene drift is so important.

    We see the same patterns in our societies. Mechanisms for mitigating the damage from things like fire, floods, crime, famine, dictators, other enemy societies, and so forth. It is said that rules are written in blood. Laws are scar tissue. From the checks and balances that stopped the megalomaniac from becoming an all-powerful tyrant to the note on the office kitchen telling you to not microwave fish. In the absence of a unifying all-encompassing task like a world war, societies seem to have evolved into a state where individuals (or loose collections of individuals in the form of companies, fandoms, etc) are sort of doing their own thing, wandering randomly through activity space most of the time, while occasionally helping out with the collective social emergencies they have expertise in.

    This is why I am often bemused by computational efforts to simulate evolution by optimising for a single trait. The classic example of this is the simulation where 2d ‘animals’ with legs and muscles were optimised for running speed, as measured by average speed of their centre of mass over a fixed distance. The winning organism evolved to be extremely tall top-heavy creature that ‘moved’ by falling over once.

    The simulated creature doesn’t have to be the fastest organism ever. It merely needs to be able to locomote to find food or avoid predators. It’s a sort of minimum viable product.

  19. Gus says:

    What a wonderful post. I am reminde dof an excellant book called “Life : an unauthorised biography” by Richard Fortey. He opens his book with

    ” ‘one tribe with bacteria that live in hot springs, parasitic barnacles, vampire bats and cauliflowers’.”

    He talks about viruses but also bacteria, how once the earth was dominated by giant pillows of bacteria floating on the seas, and that the cells of our bodies are just basically different unicellular bacteria that realised they could work in symbiosis with each other. Consciousness is anothe interesting thing we dont understand – you cannot understand the plot of star wars by analysing the capacitors in your television – and the same goes for human consciousness – that would be absurdly reductionist. Truth really is stranger than fiction and that’s why I think science is endlessly fascinating – it makes my universe more mysterious not less.

  20. Gus says:

    What a wonderful post. I am reminded of an excellent book called “Life: an unauthorised biography” by Richard Fortey. He opens his book with

    ” ‘We are one tribe with bacteria that live in hot springs, parasitic barnacles, vampire bats and cauliflowers -we all share a common ancestor.”

    He talks about viruses but also bacteria, how once the earth was dominated by giant pillows of bacteria floating on the seas, and that the cells of our bodies are just basically different unicellular bacteria that realised they could work in symbiosis with each other. Consciousness is anothe interesting thing we dont understand – you cannot understand the plot of star wars by analysing the capacitors in your television – and the same goes for human consciousness – that would be absurdly reductionist. Truth really is stranger than fiction and that’s why I think science is endlessly fascinating – it makes my universe more mysterious not less.

  21. xyr says:

    Derek, Thanks for doing these posts on the topic and I was one among many that requested.
    Also, What is your take on this
    https://www.thehindu.com/news/national/questions-remain-on-drdos-covid-drug/article34537596.ece

  22. Carl says:

    I think your being a bit unfair to some of the natural processes of the universe here by saying there’s nothing comparable to organic life and us. Look at what the universe is believed to have looked like just after the big bang and then look at it now. We went from a state of pure energy to actual matter with at least 4 distinct states and it formed all these weird amalgamations called galaxies and stars and planet, and so many different elements, how did we go from pure energy to all this different types of matter.

    It’s easy to overlook that kind of thing because the universe settled out into a form thats fairly close to what we now know billions of years before our solar system came into being. And every change thats happened since then has been happening on the same multi-billion years time scale.

    Take a perfect simulation of the universe from start till now and run it at high speed so it takes a single human lifetime to run and i bet it would look really crazy too. They’d be looking at the crazy varieties, (and yet similarities at the same time), of individual star systems the way you look at individual cells in your work.

    1. Augustine Leudar says:

      Thats true – and besides since dark matter consists of such a large proportion of the universe- who knows what complexity exists there – there may be complex forms of consciousness with entirely different bases for existence, which don’t use matter at all. Especially since”normal matter” (ie atoms) itself is a relatively rare phenomenon consisting of the only 1 – 10% percent of the known universe. As such our existance is a niche within a niche and our definitions of consciousness and life is as someone once put it ” hopelessly culturebound” . Such complex manifestations would require us to completely redefine what we consider to be “life”

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