Reading notes of Nick Lane's "The Vital Question"

In previous summer vacations, the theory group next door would launch a series of lectures that were not related to their main research work. Every Friday, they would pick up some strong people to talk about topics that had nothing to do with their main research work, such as the history of the US central bank, the natural interest rate, squirrels in the park, and stupid suburban planning represented by street-road...

As a result, this year, the boss of the next group went on vacation, the junior went to summer school, and the undergraduate sister went to Germany for exchange, leaving only one person in charge, so our boss easily usurped power and transformed this activity into a reading club that was not a waste of time. At the insistence of my loyal minister, the republican tradition of free pizza and beer was preserved.

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The book we read was Nick Lane's The Vital Question. The word "vital" in the title is difficult to translate, as it literally means important, but the vi- prefix itself has associations with life. So much so that the Taiwanese version is directly named "The Source of Life" and the Chinese version is named "The Origin of Complex Life".

As the simplified Chinese title suggests, this book calls multicellular organisms composed of eukaryotic cells "complex life", and believes that this form of life originated from an event that "happened only once in history" - mitochondrial "endosymbiosis" - an archaea cell engulfed an aerobic bacterium, and then the two survived together. The former and the latter evolved into modern eukaryotic cells together, and the latter evolved into mitochondria in eukaryotic cells.

However, this incident happened billions of years ago, and there is no surveillance video to prove the whole process, so this statement can only be regarded as a scientific hypothesis supported by evidence.

The so-called evidence includes the composition of relatively small amounts of ancient rocks and biological fossil evidence, the cell structures of a very large number of existing organisms, the comparison results of genetic information between different species, and so on.

According to Karl Popper's philosophy of science, support refers to the fact that these facts can disprove {a subset of [the negation of (the original proposition)]}. Even if it makes sense in itself, it cannot deny the existence of other possibilities. Scientists with different views base their arguments on the principle of "he who claims must provide evidence", and the academic community constructs experiments based on different predictions formed by competing theories to disprove wrong claims.

The authors believe that this endosymbiotic event is of extraordinary significance. Mitochondria, a structure dedicated to producing energy, have led to eukaryotic cells having an energy budget far greater than that of prokaryotic cells (measured by the average energy available to each gene), thus making significant "advances" in structural and functional complexity.

Not only that, the author further believes that many phenomena that are not directly related to mitochondria are also the result of this endosymbiotic event, such as the emergence of nuclear membranes, the emergence of gender and sexual reproduction, the emergence of species, the length of species lifespan, etc. However, the evidence for this part is not sufficient, and even the author is not very sure about his own argument.

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Although the author's core point is about the emergence of eukaryotes, I think the highlight of the book is the inference of the process of the cell from nothing to something. The causal chain is extremely long, but it is supported by facts. Even if you doubt it, it is hard to deny the intellectual ingenuity of this theory.

The author based his argument on the following facts:

• The universal energy currency of today's cellular biological systems is ATP ↔ ADP + Pi;
• The universal production mode of this molecule is that ATP synthase catalyzes the process of hydrogen ions (protons) crossing the biological membrane, which requires the existence of a proton concentration gradient on both sides of the mitochondrial inner membrane;
• The source of the gradient in existing biological systems is a series of redox reactions, in which electrons are transferred from food molecules to respiratory chain molecules represented by Complex I, and finally to oxygen molecules, which are located on the inner membrane of the mitochondria. The process of electron transfer transports protons across the membrane against the gradient;
• The phospholipid membrane composition of bacteria and archaea is different.
• Before the emergence of life, the oxygen concentration in the ancient Earth's atmosphere was very low and the carbon dioxide concentration was high.
• On the seabed near the center of seafloor plate expansion, the rocks exposed from the mantle by crustal movement are rich in olivine, which is rich in ferrous ions and magnesium. The oxidation of ferrous ions by water is an exothermic reaction, accompanied by the release of a large amount of hydrogen, which dissolves in alkaline seawater. This forms alkaline hydrothermal vents.
• Alkaline hydrothermal vents spew out warm water at 60°C to 90°C, and have a complex, maze-like structure of interconnected micropores.

The speculation on the process of cell emergence is given:

• Before the emergence of life, the concentration of carbon dioxide on the ancient earth was high and the ocean was acidic; the seawater near the alkaline hydrothermal vents was alkaline, so there was a relatively stable hydrogen ion/proton gradient.
• Thermodynamically: In an alkaline environment, the oxidation reaction of hydrogen molecules can proceed spontaneously; in an acidic environment, the reduction reaction of carbon dioxide to organic molecules can proceed spontaneously. (See the redox potential problem in the previous article for details.) The two are combined. Under the premise of the existence of a proton gradient, the reaction of hydrogen reducing carbon dioxide to organic matter can release energy.
• Kinetically: The metal ions on the surface of the rock near the alkaline hydrothermal vents can act as catalysts, significantly reducing the activation energy. Although the catalytic efficiency of these metal ions is low, with evolution, proteins gradually modify the metal ions, and then evolve into today's biological enzyme molecules.
• The microporous structure of the alkaline hydrothermal vents has a thermophoresis effect, which can make organic molecules highly concentrated and help the reaction rate. The micropores can also allow lipid molecules to spontaneously form vesicles, encapsulating various organic molecules and forming the prototype of cells.
• (At this time, there was no genetic information and its replication, and this theory did not explain the evolution of genetic information molecules, but it can be inferred that biochemical reactions became increasingly complex with evolution, and substances and structures related to biological information such as DNA, RNA, and ribosomes appeared.)
• Among them, the catalyst for hydrogen to reduce carbon dioxide evolved into energy-converting hydrogsase (Ech* for short), which is responsible for carbon metabolism. It is embedded in the primitive cell membrane and completes catalysis in the process of protons entering the membrane from outside the membrane. This mechanism is still used by methanogenic bacteria today.
• Similarly, ATP synthase is also embedded in the primitive cell membrane, catalyzing the synthesis of ATP in the process of protons entering the membrane from outside the membrane, responsible for energy metabolism.
• The membrane structure at this time cannot prevent protons from crossing the membrane, and it cannot rely on itself to maintain the proton gradient, so it can only exist near alkaline hydrothermal vents.
• Later, early cells evolved an antiporter that exchanges a sodium ion for a hydronium ion across the membrane. The hydrogen ion concentration outside the membrane is higher than that inside the membrane, so hydrogen ions enter the membrane from outside the membrane; sodium ions leave the protocell and cannot diffuse through the protocell membrane, but their size is similar to that of hydrated hydrogen ions, so they can return to the membrane through Ech and ATP synthase to drive carbon metabolism and energy metabolism.
• This method reduces the dependence on the external hydrogen ion concentration and expands the survival range of the protocell.
• Then the differentiation of bacteria and archaea appeared:
  • The ancestors of acetogens (bacteria) reversed the direction of Ech, making it a proton pump that maintains proton concentration and consumes energy, and uses other mechanisms for metabolism.
  • The ancestors of methanogens (archaea) evolved a new proton pump to transport protons out, and still use protons through the original Ech for carbon metabolism.
• The two organisms adopted different ways to maintain proton concentration, which led to the independent evolution of membrane selectivity, different structures of phospholipid molecules, and different cell wall compositions.

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It can be seen that our boss is very convinced by this theory. When the lab was just established and still under construction, he could only introduce this hypothesis to us during the journal club. After that, we also read several papers that refuted the views in the book, as well as the responses and further rebuttals from the authors and their supporters.

Yes, there is a large group of forces in the academic community that have strongly criticized this theory:

First of all, the idea that the evolution from prokaryotic cells to eukaryotic cells is a kind of progress is no longer in line with modern biology’s understanding of evolution. Even this word is no longer generally understood as some "progress", but a mroe neutral "process".

Secondly, using the "average energy available to each gene" as the standard for the superiority of eukaryotic cells is a bit like shooting the arrow first and then drawing the target.

Although the main points of the affirmative side are collected in this book, and the opposing side mainly publishes their arguments in academic journals, giving people the impression that civilian scientists are fighting against official scientists, the two sides have engaged in direct written battles in some top biological journals, and both sides are insiders in biological research.

I read those rebuttal papers a long time ago, so I am just summarizing them here based on my memory. If I am still interested in this issue in the future, I may go back and read them again.

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Since the endosymbiotic event is the main character of this book, and it is located in the middle of biological evolution in time, the order of the book's writing can easily make people lose their sense of time.

I had originally intended to reorganize my notes and write them in a chronological format, but a large portion of this book is devoted to discussing causes, mechanisms, consequences, and so on, and after trying it I found that the effect was not very good.

Moreover, the author's writing ideas are also very jumpy, often going off topic for a while, and then seamlessly returning to the previous topic later...

I dare to speculate the reason, maybe the author wrote the first draft first, and then watered it down under the coercion and inducement of the editor~

This led to the fact that during the weekly discussion time, many of the questions they raised were already written by the author in the book, and I had to refer to the notes I made when reading the Chinese version, go back and find the chapters in the English version, and point them out.

Of course, it is also possible that my personal Chinese reading ability exceeds the English reading ability of others, but the others here include my boss, so I think it is unlikely~