Friday, February 03, 2017

Why is life the way it is?

Nick Lane is very good at explaining complex biology and biochemistry. He is the winner of the Royal Society's Michael Faraday Prize for 2016. Here's his lecture. It's worth watching if you want to understand the latest informed (naturalistic) speculations on the origin of life.




37 comments :

  1. I wonder if Lane feels any discomfort in being associated with a fundamentalist cracker like Faraday.

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  2. I read Nick Lanes's The Vital Question, and there's something that puzzles me, which relates to this article: The energetics of genome complexity, Nick Lane & William Martin, 2010. (http://www.nature.com/nature/journal/v467/n7318/abs/nature09486.html)

    They do a back-of-the-envelope calculation. Prokaryotes metabolise about 3x faster than eukaryotes in terms of watts/g, but eukaryotic cells are 15,000x bigger, so eukaryotic cells have 5000x times as much power in terms of watts/cell. Eukaryotes have 4x as many genes as prokaryotes, so they have 1200x as much power per gene.

    About 80% of a cell's power is used for making proteins, so it seems eukaryotes make about 1200x as much protein per gene. I started wondering about the mechanics of that. Transcription rates and translation rates per nucleotide are at least as fast in prokaryotes, and there's no introns to transcribe or splice out, so you'd think prokaryotes would make more protein per gene, not 1200x less.

    Eukaryotic cells cells live longer of course, and most are diploid, so have two copies of each gene. Some are polyploid or multinucleated - and I think Lane and Martin's "15,000x bigger" includes some eukaryotic cells with lots of nuclei. A fair comparison would be of (rate of protein synthesis)/(gene copy).

    So I got some numbers, from the book Cell Biology by the Numbers, and the biomumbers site (http://bionumbers.hms.harvard.edu/). I found it easiest to get figures for cell volumes. I assume (protein weight)/volume is similar for these cells. They are for organisms when they are growing fast (but not as fast as possible). V = volume in um^3 per gene copy per hour.

    E Coli: volume 0.7 um^3, #gene copies 4400, doubling time 1h. V = 1.6e-4
    Budding yeast: volume 37 um^3, #gene copies 6000, doubling time 3h. V = 20e-4
    C Elegans: volume 1800 um^3, #gene copies 40000, doubling time 10h. V = 45e-4
    Euglena gracilis: volume 3700 um^3, #gene copies 60000, doubling time 12h. V = 50e-4

    It seems that these eukaryotic cells make protein 10-30x faster than E Coli, per gene copy. Looks very odd to me. Presumably the limiting factor for prokaryotes is power, as Lane and Martin suggest. Apparently prokaryotes have the molecular machinery to make protien faster than eukaryotes, but they hardly ever have enough energy to run the machinery anywhere near full speed. I feel I must have miscalculated something, or be ignorant of something important, and it's bugging me!


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    1. Try thinking in terms of proteins made per ribosome. Then, to rationalize why eukaryotic cells have so many more ribosomes, try to estimate ribosomes made per ribosomal gene copy.

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    2. This seems like a relatively pointless discussion to me. A typical generation time for bacteria is several days or maybe even weeks. Most of the protein in the cell is very stable and doesn't need to be constantly made (e.g. ribosomal proteins, transporters, DNA polymerase, electron transport complexes, pyruvate dehydrogenase). As a result, the typical bacterial cell is only making enough protein to replace those that turn over fairly rapidly. That's only a small percentage of its potential capacity.

      Contrast this with yeast cells that are doubling every hour or with cells in a growing mammalian embryo. Those cells are churning out protein (plus lipids, nucleic acid, and carbohydrate) at an enormous rate.

      The rate of protein synthesis will depend on the supply of energy in all cases. It seems pretty obvious to me that the potential rate under optimum conditions will be much higher than the rate under normal conditions.

      Where's the beef?

      BTW, the rate of transcription in this case is the number of transcripts produced per minute. At steady-state levels, that is determined by the number of initiations per minute since many transcription complexes can be transcribing a gene at the same time. Thus, the rate is independent of the size of the gene or the presence of introns.

      BTW, in most complex eukaryotes only half (or fewer) of the genes are being expressed in any one cell type. Even in E. coli there are a fair number of genes that are silent (repressed) under certain conditions.

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    3. Larry,

      In transcription and translation, there must be some sort of trade-off between energy efficiency, speed, and accuracy. If bacteria don't need much speed (because they never have the energy to exploit it), they should have evolved molecular mechanisms which work slower, but are more energy efficient and/or more accurate. They have not done this, and I think that demands an explanation.

      If you look at bacteria which grow more slowly, they should have evolved even slower mechanisms. I don't have numbers for such organisms.

      On your first BTW: good to know. I was trying to get a picture of how parallelised the process in eukaryotes are, and that helps. Still, bacteria use more parallelism than eukaryotes.

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    4. If bacteria don't need much speed (because they never have the energy to exploit it),

      Not sure of the apples/oranges issue here. Bacteria need to keep up with their neighbours. Any slowdown will see them outcompeted. Eukaryotes have a different ecological dynamic - they aren't diffusion limited and directly competitive for raw 'building blocks'; many of them engulf entire organisms for fuel. They need to be better at that. Bacteria are on the breadline; eukaryotes comparative 'fat cats'.

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    5. Let's keep in mind that when we're talking about eukaryotes in this context we are referring to single-cell eukaryotes who also have to keep up with their neighbors.

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    6. @Larry

      Absolutely - that specifically was in my mind. But their ecology is nonetheless different from that of their prokaryote neighbours. They are some 10,000-50,000 times bigger, for one, and that don't come cheap. It is arrived at by consumption, which gives a significant change in dynamic, well before one starts to look at multicellular versions.

      Prokaryote/eukaryote energy budgets are not directly comparable.

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    7. An important point to consider is that there are a large number of heterotrophic flagellates that can be <<10 microns across and which harbour very few mitochondria. This size range of eukaryotes is rarely considered in these energy budget discussions. Also, for a different take on the energetics discussion have a look at Lynch and Marinov (2015) :https://www.ncbi.nlm.nih.gov/pubmed/26575626

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    8. Ah -- you've already blogged about that paper! Note that none of these authors have considered very small eukaryotes in their calculations. In my view this is critical to understanding eukaryogenesis. It doesn't really matter what the 'average' size of eukaryotic cells are...it matters more what the size of the last eukaryotic common ancestor was. If this cell was < 50x the volume of the last common ancestor of euks and the closest related archaeal cells, then all of the scaling arguments change.

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    9. I read your comment with great interest, Graham. I have not read The Vital Question, but I have read various other papers that Nick Lane has written. They tend to be about the need for energy when the number of genes are increasing, and they conclude that mitochondria are needed for eukaryotes. I have analyzed the New Scientist paper from 23. June 2012: "Life: Inevitable or fluke?". I think it is quite similar to the one you are referring to. I found that there is no need for extra membrane area for eukaryotes, and especially not for eukaryotes as compared to bacteria. I instead concluded that mitochandria are not needed for eukaryotes. Quite contrary,  my blog has other explanations, e.g. the Organelle Escape Theory, which explains relations between bacteria and organelles at least as well, or probably better than Margulis´ theory.

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  3. Professor Moran, what's the best known example of a beneficial mutation?

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    1. The easiest ones to understand are mutations to antibiotic resistance in bacteria.

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    2. I'm looking for specific examples, not necessarily easy ones, where genetic information is added, not destroyed.
      For example, if resistance is the consequence of the breaking of a genetic switch, then it's not a very useful example.

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    3. hety89:

      Why don't you first provide a robust definition of what you consider to be genetic "information", and what an example of "addition of genetic information" would look like. Once you've done so, give yourself a big medal for being the first creationist to ever actually accomplish this feat.

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    4. (Sorry for mistyping your name, BTW.)

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    5. lutesuite, I don't care, what's your angle on this, I'm just looking for some food for thought. Have you got anything, that I might find interesting?

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    6. I doubt I have anything you'd be able to comprehend, never mind find interesting. But, for my own amusement, show me what kind of convoluted apologetics you have to resort to in order to explain this away as an example of "addition of genetic information":

      http://pubmedcentralcanada.ca/pmcc/articles/PMC4392837/

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    7. That's a good one.
      To begin with, I'll try to ask, how many mutations did it take to get from function A to function B.
      What path did a specific gene copy take through the fitness landscape?
      Was it a random walk?
      etc. I'll ask many questions, before I form my opinion.
      But it's definitely food for thought. Thank you.

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    8. What I've learned from this article, is that
      a random walk more commonly involves the insertion and deletion of longer segments,
      and a few point mutations. (instead of just point mutations, which is what I assumed from listening to ID advocates).
      The mechanism involved in these mutations is not radiation, nor any mutagenic agent. It's just what the cell normally does.
      The way those sequences evolve, reminds me of hacking, which gives credence to a theory, about which (believe it or not) I learned today.
      cosmicfingerprints.com/blog/
      Mostly, his book is just boring. It contains some interesting ideas, but there wasn't mouch flesh put on them.
      http://libgen.me/view.php?id=1393546

      That's why I needed some examples to study, but, preferably, with multicellular organisms.

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    9. Perry Marshall is an ignoramus. Ignore him. Better to try and learn from competent mainstream biologists, several of whom post here regularly (I'm not one of them, I hasten to add. I'm just a reasonably well-informed amateur.) There are also ignoramuses who post here, but its usually pretty easy to tell them apart from the folks who know what they're talking about.

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    10. He does seem to have that aura. But how do you know, that his ideas are garbage?

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    11. Because I've read about them and I understand biology. Here's what happens when he tries to take on one of those competent mainstream biologists I was talking about:

      http://freethoughtblogs.com/pharyngula/2016/01/12/my-last-post-on-perry-marshall/



      Why don't you cite the experimental finding that you think best supports his claims?

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    12. I'm not even sure, what's his claims are. None of his ideas seem to be originating with him.
      In his book, he's basically saying the same thing as
      Gregory Chaitin in Proving Darwin: Making Biology Mathematical
      http://libgen.me/view.php?id=842218
      , but dressing it up in a theistic light. That I find entirely appropriate. But there's almost nothing original about this guy.

      To answer your question: I'm citing Gregory Chaitin's book. But it's a piece of theoretical works, not experiments, so decide for yourself, if it's reliable or not.

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    13. It's interesting: Chaitin proposes a way to differentiate between different hypotheses for the cause of evolution.

      "in our Busy Beaver toy model of evolution it turns out that the organisms that evolve are better and better approximations to the halting probability Ω—lower bounds, in fact—because these are the fittest organisms. And intelligent design obtains N bits of Ω in time N, which is the best possible; exhaustive search, which stumbles about trying everything, obtains N bits of Ω in time 2^N; and cumulative random evolution obtains N bits of Ω in time between N^2 and N^3."p.43

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    14. For example, if resistance is the consequence of the breaking of a genetic switch, then it's not a very useful example.

      What if it's the result of plasmid exchange?

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    15. judmarc
      Maybe? Could you be more specific, please?

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    16. https://www.sciencedaily.com/releases/2011/04/110411163918.htm

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  4. Why do you add "naturalistic" in the last sentence in your post about speculations? Do you add it because alcaline vents were found and tested?

    Thank you for posting this extremely well done lecture. I read "The vital Question" as well and think it is a very plausible theory. Also the part about the separate origine of (the membranes) of Archaea and bacteria that is well documented and illustrated in the following article:

    A Bioenergetic Basis for Membrane Divergence in Archaea and Bacteria
    Sojo V, Pomiankowski A, Lane N (2014) A Bioenergetic Basis for Membrane Divergence in Archaea and Bacteria. PLOS Biology 12(8): e1001926. doi: 10.1371/journal.pbio.1001926

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    1. I added "naturalistic" because there are many non-naturalistic explanations of the origin of life. Most scientists ignore them but we discuss them frequently on this blog. I didn't want the. Creationists to get their hopes up! :-)

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  5. My professor of Quantum Mechanics, who is a cosmologist but occasional Origin of Life researcher, James Trefil, argued life is the way it is because of frozen accidents. I suppose he meant it could have taken different forms, but the form we have today is because that was the accident that was frozen.

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    1. I don't think "frozen accident" is that useful a concept here. The generally used notion is "contingency", which I think better communicates the idea you want to get across.

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    2. Contingency means that everything depends on what came before—a lesson learned by Jimmy Stewart in "It's a Wonderful Life."

      Frozen accident refers to the origin of the genetic code. Did it evolve for specific reasons such as matching the properties of an amino acid to a particular codon or did the assignment of codons arise pretty much by accident that was subsequently frozen in place because change was difficult.

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  6. Larry

    so, do you believe that ? was it a " frozen accident " because change was difficult ? The change from two to three codons was not difficult, but further change was, that why it suddenly froze and stopped changing ? What was the mechanism that gave rise to the genetic code and , subsequently the translation system and ciper ?

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    1. It's quite simple, Otangelo.

      If you have a simple structure consisting of two blocks sitting next to each other, you can easily move one or the other around without the entire structure collapsing.

      However, if you build a complicated pyramid atop those two blocks, it is no longer possible to move either of them without causing the pyramid to fall.

      Clear now?

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