[HN Gopher] Using paleogenomics to elucidate 10k years of immune...
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       Using paleogenomics to elucidate 10k years of immune system
       evolution
        
       Author : gmays
       Score  : 29 points
       Date   : 2023-01-16 16:46 UTC (6 hours ago)
        
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       | remote_phone wrote:
       | The immune system is one of the reasons why I stopped believing
       | in large scale evolution. I still believe small scale evolution
       | exists, but I do not believe that our immune system came about
       | randomly.
       | 
       | There are two main factors to our immune system that protect us:
       | 
       | 1) all our cells are marked uniquely and exactly the same across
       | every cell in our body. Every human, and I think every animal,
       | has this same feature where all cells are marked the same. But
       | unless there was an immune system to enforce this, it has no
       | value. If it were random you would expect every cell to be marked
       | randomly but it's not.
       | 
       | 2) our immune system is designed to attack anything that isn't
       | marked with that unique identification. If we had random
       | identification per cell, the immune system we have couldn't be
       | created.
       | 
       | This system couldn't be designed separately. It's essentially a
       | single transaction two-step evolution that simply couldn't have
       | been done randomly at different points in time. If you created an
       | immune system that attacked things that weren't marked the cell
       | across all cells, the organism would die because the immune
       | system would attack itself the way transplant patients would. The
       | immune system we have couldn't be created unless all the cells
       | were marked the same.
       | 
       | Both parts (unique identification are the same across all cells,
       | and the immune system that attacks any other things that aren't
       | marked the same) must have been created at the same time.
       | 
       | If anyone has any counter arguments I would love to hear it
       | because I've been thinking about this long and hard during Covid
       | and couldn't think of anything else.
        
         | pazimzadeh wrote:
         | The fact that each of our cells has an identical unique marker
         | (you must be referring to the MHC?) is not the basis of how the
         | immune system functions. Instead, during development in the
         | thymus, lymphocytes carrying a wide _variety_ of unique immune
         | receptors are exposed to proteins from all over your body
         | (heart protein, lung protein, etc..) and any lymphocyte that
         | reacts with self is killed (negative selection), thus leaving
         | you with remaining cells which which do not react to your body.
         | https://en.wikipedia.org/wiki/Autoimmune_regulator
         | 
         | The fact that the MHC regions is so diverse is just another
         | layer of security which prevents major biases within the
         | population in the presentation of chopped up bits of foreign
         | and self antigens. However if we all had the same MHC, the
         | function of the adaptive immune system would remain intact.
         | Plus, we would be able to transplant organs between people much
         | more easily.
         | 
         | The basis for the existence of these varied adaptive immune
         | receptors which perform the recognition of self vs non-self is
         | under investigation and you might want to read up on the latest
         | research before jumping to conclusions:
         | https://europepmc.org/article/pmc/6084782
         | 
         | If I remember correctly though, one of the major hypotheses is
         | that an ancestor of the HIV or similar virus or transposon
         | integrated itself within the gametes of some jawed fish without
         | killing it, resulting in the ability to generate variation in
         | immune receptors. https://pubmed.ncbi.nlm.nih.gov/7584143/
         | 
         | Oh, and there is not just one way to have an adaptive immune
         | system, as even jawless fish have a way of rearranging their
         | receptors to generate diversity:
         | https://pubmed.ncbi.nlm.nih.gov/15241406/
         | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805090/
         | 
         | In sum, the only GOD we have evidence for around in the
         | Generation of Diversity.
         | https://www.nature.com/articles/430157a
        
         | [deleted]
        
         | AdrianB1 wrote:
         | "came about randomly" is a strange statement; natural
         | selection, where you filter out weaker specimens of the species
         | in favor of the stronger ones is not random, it is a long time
         | process.
        
           | the-printer wrote:
           | I don't necessarily follow everything that the parent comment
           | is covering, but I gather that he may be referring to the
           | sheer existence of the immune system. How can natural
           | selection account for that?
        
             | pazimzadeh wrote:
             | There is no "immune system." There is an innate immune
             | system which reacts quickly but only to general threat
             | patterns (kind of like racial profiling, to be crude). It
             | is really easy to explain the evolution of this system.
             | 
             | The adaptive immune system is the one that runs a mini-
             | evolution within your own body as way to counter the
             | extremely rapid rate of evolution in pathogens. There are a
             | few explanations as to how this came about - see my last
             | comment.
             | 
             | Paradoxically, it may be the very success of our immune
             | system which puts selective pressure on pathogens to evolve
             | even faster.
             | 
             | The acquired immune system: a vantage from beneath
             | https://pubmed.ncbi.nlm.nih.gov/15539148/
        
             | fernandopj wrote:
             | You're making the same mistake as the OP: looking in
             | isolation at the current, final step of a process that took
             | millions of years. Also, you're gonna find a lot of
             | different immune systems in nature, just as you can find
             | many different eyes/vision in animals. There's a lot of
             | middle ground in species that saw no advantage in evolving
             | that particular system against their environment.
             | 
             | You're also confusing the randomness of the steps with the
             | somewhat previsible trend of an entire ecosystem which is
             | evolving. If world is getting warmer and air more dense,
             | you wouldn't be able to guess which mutation occurs but you
             | can predict in time animals would be more adapt to that new
             | ecosystem.
             | 
             | Darwin famously looked at a unusual orchid with a long
             | "tube" leading to nectar, and spoke that "there must be a
             | bird with a long beak here somewhere". He didn't find it at
             | first, but it was discovered later [1]. So you can apply
             | some predictions at how evolution took place if you take a
             | look at the environment. Just as one would guess there must
             | be an immune system in animals if you discover diseases,
             | virus, bacteria etc - or else how would large animals
             | exist?
             | 
             | [1]https://laidbackgardener.blog/2017/04/12/darwins-orchid
        
         | mrkeen wrote:
         | > I stopped believing in large scale evolution. I still believe
         | small scale evolution exists
         | 
         | It's always been small scale, the whole time.
         | 
         | Otherwise you'd have the bizarre discontinuities that people
         | like to straw-man evolution with. Like a fish that just decides
         | to walk out of the ocean and breathe air one day.
        
         | pvg wrote:
         | This argument is 'irreducible complexity' from Intelligent
         | Design, a pseudoscientific attempt to shoehorn creationism back
         | into science education.
         | 
         | https://en.wikipedia.org/wiki/Irreducible_complexity
         | 
         | is a good starting point, of course you can also just google
         | 'intelligent design' and go from there.
        
         | 1auralynn wrote:
         | You're not understanding the timescale or the context of the
         | immune system's evolution. Imagine a cluster of unicellular
         | organisms forming a multicellular organism for the first time.
         | A multicellular organism stands a much better chance of
         | survival than a single cell. Imagine a mutation that resulted
         | in a cell surface protein that indicated cells were "friendly"
         | and maybe even allowed them to glom together.
         | 
         | Later on, a billion or so years later after the system of cell
         | surface proteins have grown in complexity, imagine a
         | multicellular organism like a sponge, where the ocean flows
         | freely through the inner compartment, helped along by simple
         | differentiated cells containing primitive cilia/flagella. Some
         | of the cells that line the wall of the inner compartment become
         | proto-macrophages, capable of "eating" foreign objects that
         | flow through. The context here is that the immune system has
         | deep ties with the digestive system evolutionarily. So, a ton
         | of the functionality of the immune system has an overlap with
         | the digestive system... "self vs not self" goes way back.
        
         | meindnoch wrote:
         | The cells of an organism can have attributes that are:
         | 
         | 1. unique to each individual cell
         | 
         | 2. unique to the organism, but identical among its cells (i.e.
         | cells descending from the same egg cell)
         | 
         | 3. identical among all members of the species, or even across
         | species
         | 
         | Any immune system will _necessarily_ evolve to use the
         | attributes from group #2. If it were to use #1, the organism
         | dies. If it were to use #3, then rogue cells from other
         | compatible organisms can infiltrate and steal the organism's
         | resources, which is evolutionarily disadvantageous (unless it's
         | a beneficial relationship, c.f. gut microbiome).
        
         | Drakim wrote:
         | Usually when there is a two-step process needed for something
         | to evolve, then there is often an advantage to one of the steps
         | in isolation that isn't easily apparent, or the advantage it
         | gave might have been lost to time.
        
         | stevenhuang wrote:
         | I think you need to learn more about the immune system.
         | 
         | But to continue your analogy, it doesn't need to be a two-step
         | process. You can start with an immune system and "randomly
         | marked" cells (they're not random, but say they are). Millions
         | of cells are created by your body every second. The cells that
         | are marked "incorrectly" will die off, leaving those the immune
         | system recognizes to continue reproducing. Overtime the
         | remaining cells DNA will only contain instructions to create
         | new cells "marked" to not provoke an immune response.
         | 
         | Why is one such counterexample so unthinkable a process to you?
        
         | flobosg wrote:
         | Note that there are two different types of immune systems:
         | innate and adaptive, which work together to protect against
         | pathogens. It seems that you are conflating both.
        
       | DoreenMichele wrote:
       | This is just a press release, so a general overview. It's not
       | that deep.
       | 
       | It's sort of a pet peeve of mine that _the immune system_ doesn
       | 't mean what most people seem to think it means.* However, it's
       | already been established that certain mutations -- even deadly
       | mutations -- are more common due to improving odds of survival
       | against specific infections that swept specific regions
       | historically.
       | 
       | So, "survival of the fittest" doesn't mean what a lot of people
       | think it means. It's rooted in a _winnowing_ process where those
       | who don 't die get to pass on their genes. That's all it means.
       | 
       | Cystic fibrosis is a predominantly Caucasian genetic disorder.
       | Studies suggest this is so because, like Sickle Cell protects
       | against malaria, it protects against tuberculosis and I think one
       | other disease but I'm not remembering which one nor readily
       | finding a reference.
       | 
       |  _Cystic fibrosis carriership and tuberculosis: hints toward an
       | evolutionary selective advantage based on data from the Brazilian
       | territory_
       | 
       | https://pubmed.ncbi.nlm.nih.gov/28499359/
       | 
       |  _Cystic fibrosis gene protects against tuberculosis_
       | 
       | https://www.newscientist.com/article/dn10013-cystic-fibrosis...
       | 
       | So this is already fairly well established. Cystic fibrosis is an
       | inflammatory condition, which fits with their observations.
       | 
       | ----
       | 
       | * ..."the immune system" doesn't really mean a specific set of
       | organs like "the circulatory system" or "the digestive system"
       | means a specific set of organs. It's just kind of a catch phrase
       | for "how the body protects itself" and it's not really that well
       | understood or explained exactly that happens.
       | 
       | https://news.ycombinator.com/item?id=25167263
        
         | flobosg wrote:
         | > it protects against tuberculosis and I think one other
         | disease but I'm not remembering which one
         | 
         | Cholera and typhoid fever are other candidates:
         | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2358959/
        
         | jyscao wrote:
         | >it protects against tuberculosis and I think one other disease
         | but I'm not remembering which one
         | 
         | I recall reading long time ago that carriers of CF are
         | hypothesized to be more resistant against cholera.
        
       | pazimzadeh wrote:
       | I'm kind of disappointed that there's no mention of cancer in the
       | article. The rise of cancer (presumably due to increased nutrient
       | availability following agriculture?) could be a reason why the
       | immune system may have started skewing towards autoimmunity.
       | 
       | In fact, several microbes have been found to have anti-cancer
       | properties - either directly of by stimulating the immune system.
       | So maybe success in tackling pathogens led to a deficit in
       | combatting the enemy within.
       | 
       | Otherwise, it's not exactly clear why the ability to fight off
       | pathogens (foreign bodies) would necessarily lead to an increase
       | in autoimmunity (attacking your own cells).
        
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       (page generated 2023-01-16 23:01 UTC)