the vital question 2

main takeaways

• the fact that all the cells have same way of producing energy(chemiosmotic coupling) and it can be tied to origin of life, where geochemistry and biology almost merge is fascinating
• once prokaryotes formed, they stayed the same way for ~2 billion years- for half the time life had existed. For nearly half the time, life was primitive! The jump to eukaryotes was a key step. Nick Lane presents arguments that endosymbiosis led to things the way they are now - 2 sexes, nuclear membrane, germline and soma cell seperation, aging and death
• It is tempting to think evolution as continuous process where mutations eventually lead to complex life. But this shows that there are sometimes discrete events that are actually needed to achieve complexity.

origins of life

• all living cells- plants, humans, microorganisms use ion gradients across membrane as core energy system. Why is this same from simple to complex forms of life?
• this was because of the way life started. ~4 billions years go at alkaline hydrothermal vents, inside vents alkaline and outside sea acidic. Due to his difference in concentration gradient, protons use to move across and this electromotive motive force was used to drive metabolism. Basically early life took advantage of the naturally existing gradients. “Its a free lunch, that you are paid to eat for - Everett Shock”
• The early metabolism was very basic(something called acetyl CoA pathway). Fe, Ni, S minerals in vents helped as catalysts, and the natural proton graident was used to drive this reaction between $H_2$ and $C{O}_2$ . Reducing carbon. (Geochemistry and Biology were so intertwined here)
• Then slowly antiporter evolved, instead of relying on natural gradients, this antiporter pump could pump out sodium when a H+ comes in. Now, proton gradient is sodium gradient.
• Protons leak easily through membrane, but sodium doesn’t. So now, it means u could use this pump to store energy. So now they are less reliable on natural proton gradients and could evolve tighter membranes and leave their home(the vents).

Eukaryotic cell formation

• So early cells emerged into archea and bacteria. because they evolved under slightly different conditions after coming out of vents, thy have different types of membrane and other difference.

• But at one point, a bacteria entered archeaic host cell and started living together with it. This bacteria later became the well known mitochondria.

• This very rare event led to all complexity: origin of nucleus(debated: https://pmc.ncbi.nlm.nih.gov/articles/PMC10732040/), 2 sexes, germline cells and somatic cells.

• How nuclear membrane was formed as consequence of this endosymbiosis(Martin-Kooman hypothesis)

  • when bacteria entered archea, it released a lot of genes
  • these bacterial genes also became part of archea, but a lot of them were useless- they don’t code for any proteins. Such genes are called “introns”(more specifically, introns are interrupting sequences inside the gene)
  • such random genes in middle while translation could lead to non-sense proteins
  • so before translating genes, these useless genes need to be cut out. (introns are like prompt injections in the context, need to be cleaned)
  • Hence RNA scissors evolved
  • But RNA scissors are slow, and ribosome is fast in translation. So to prevent those non-genes to be translated a membrane evovled so that after transcription, these can be cut by RNA scrissors, and then sent to translation
  • These membrane had to be imperfect because it should allow the RNA to reach ribosome after transcription

• Now where did this nuclear membrane come from?

  • After the endosymbiotic bacteria entered, it released a lot of genes in the host cell. And some of them were even translated by the ribosome of the host cell
  • And some of those genes were for making a membrane. Those membrane stayed up and later evolved into nuclear membrane.
  • Evidence: nuclear membrane has kind of bacterial gene origin

• Endosymbiosis leading to germline(cells for reproduction) and somatic cells(neurons, kidney cells, liver cells…)

  • once the bacteria was making ATPs for the host cell, there was no shortage of energy
  • In multicellular organisms, cells started developing into 2 different kinds of lineages - germline: mainly for reproduction, somatic cells: cells that were created so that they can help the germline cells replicate(build and maintain the body.)
  • sponges where u can cut any part, and it regrows. But its not like that in many animals we know. Its because sponges(which are early in evolution), the seperation between germline cells and somatic cell seperation didn’t evolve yet(*Deadpool cells the reproduce after injury) also (analogy: startup where everyone does everything changed to large company where there is special team for everything)

• Why did 2 sexes evolve?

  • one for nuclear genes(given to offspring by mixing) and other to provide mitochondia(not a good idea to mix)
  • So Mitochondria to the offspring is only received from the mother.
  • Nuclear genes are mixed between mother and father
  • Reason: There is always tension between 2 forces
    • You need to have variance enough so that you can try many variations and see which one survives. If its like cloning, where all cells are same. Any change in environment, all of them perish. But if they are different, some of them might survive and continue their genes. Hence u need to increase the variance of genes
    • But if u increase too much, there might be mutations tht could be harmful. Mutations in mitochondria - the energy production is a key step, and shouldn’t be messed up. Hence its from a single parent.
    • So at one point, when both parents gave mitochondria, one of them got digested within and other got passed onto offspring
  • Hence only 2 sexes, what will the 3rd one do ( mixing of nuclear genes, and single inhertiance of energy production related genes(mitochondrial genes))

• Nicely summarised by chatgpt:

  • mitochondria are not just batteries; they changed the rules of genome complexity, inheritance, sex, ageing, and multicellularity.

Counter arguments to Lane’s hypothesis

https://pmc.ncbi.nlm.nih.gov/articles/PMC5557255/ Lane argues that endosymbiosis continued because of advantage of energy per gene. But the authors argue that while this may be one benefit, it does not explain how other problems like

• why didn’t the bacteria exploit the host
• why didn’t the host eat the bacteria they claim that the hydrogen hypothesis is more likely. It states that bacteria produced hydrogen as waste product, while archea needed hydrogen. So, archea kept bacteria so that it kept getting hydrogen.(https://chatgpt.com/share/6a01df3f-3f18-8391-8c70-bf0d1de0c52a)

Archea needed hydrogen to fix carbon dioxide ( CO2 + H2 → CH4), but this does not mean that the host cell was methanogen archea. its suspected that it is some “asgard archaea” bcoz of

Asgard archaea to hydrogen is that some reconstructed Asgard genomes encode hydrogenases, enzymes that handle H₂. A 2024 study on soil-associated Asgard archaea found expressed genes for [NiFe]-hydrogenases, pyruvate oxidation, and the Wood–Ljungdahl pathway, and concluded that some soil Asgards may be non-methanogenic acetogens rather than methanogens

Power and death

the central argument is that nucleus and mitochondrial genes had to co-adapt/co-evolve to work together

• for a cell to produce energy, the mitochondria has to work properly, mitoconndria comes from female, while nuclear genes come from both male and female.
• So it is necessary for them to co-adapt/co-evolve genes. If nuclear genes change, and mitochondrial genes don’t change accordingly then cell might die
• Nuclear genes change very slowly, while mitochondrial genes change fast(may be because they are small) . so nucleus has to adapt
• nick lane says coadaption is the reason to explain Haldane’s principle
  • if 2 related species mate, then the gender with 2 different genes will be sterile or weak
  • classic explanation: there is no other copy of that gene to help if there is a damage in one of the genes in one chromosome(XX and XY)
  • males(XY) have high metabolic rate than female. to meet those demands, cells work themselves upto death. release free radicals, release cytosome c, and triger apoptosis. (this is good to happen at embryo level, kill the cells that can’t match energy demands)
• free radical theory of aging
  • rats and pigeons are of same size, same basline metabolic rate
  • but rats survive for 5 years, while pigeons for 35 years
  • known theory is high free radicals in rats
  • the threshold hypothesis of Nicklane
    • if mitochondria cannot match the metabolic needs, cell works a lot trigger free radicals hence apoptosis
    • but what if at one points, cells are ok with certain amount of free radicals
    • this is fine for an animal like rat, where it doesn’t have to make high energy demand to fly like pigeon. so don’t have to trigger cell death, just some extra free radicals lying around
• the above statements seem to say “free radicals are bad, cause of early death(low lifespan)”. but its not true
  • free radicals are also necesary for mitochondrial replication. so free radicals can make more mitochondra to meet tthe energy requirements
  • and so if u try to remove those free radicals using anti-oxidants, it can be counter productive