Energy, Evolution, and the Origins of Complex Life.

By: Nick Lane

Published: 2015

Read: 2019

Summary:

Why is life the way it is.

Complex life on earth probably arose once only from a single common ancestor. We don’t know how this ancestor evolved and why it evolved only once. We don’t know how we got from simple bacteria to today’s complex life.

In trying to answer these questions, this book argues from the first principles of physics and (mainly) chemistry to explain historical observations and speculate on how the structural energy demands of “living” drove the emergence of simple life and then restricted the evolution of complex life.

• Energy: the continuous driving force of life.
  • All life on earth relies on the same (chemical) processes to generate energy.
  • These processes are unceasing chemical reactions requiring a constant flux of carbon and energy.
• Very few natural environments meet the requirements for life to emerge.
  • Continuous flow of carbon and energy, catalysts, concentration of end-products.
• On earth, this environment was likely underwater hydrothermal vents.
  • Heat + inorganic carbon -> the first organic carbon molecules.
• This type of environment is probably replicated elsewhere in the universe.
  • All you need is rock, water and CO2 – three of the most ubiquitous substances.
• From the beginning, emerging life depended on the flow of electrons and protons.
  • Energy is generated by the flow of electrons from (H2 to CO2; redox chemistry).
  • Energy is captured (partly and temporarily) by creating different amounts of protons on the sides of vent walls (the origins of chemiosmotic coupling).
  • Energy is applied (from the collected proton pools) to form the first organic matter (molecules).
• Simple cells emerged at the vents, applying the same energy principles as the vents:
  • Electron transfer and proton power moved inside the (leaky) walls of these proto-cells.
  • The cell’s leaky membranes allowed for a constant flow of electrons and protons in and out of the cell.
  • But a reliance on these flows kept proto-cells constrained to life at the vents.
  • Cells eventually evolved proton pumps, cutting their reliance on vent flows.
  • Proto-cells then spread and colonized the oceans and rocks of early earth.
• All simple life on earth uses the same chemistry to generate and store energy.
  • Huge versatility: simple cells “eat” and “breathe” a wide variety of substances.
• It is likely that living cells on other planets rely on the same biochemistry.
  • The emergence of simple life is predictable and likely, here and elsewhere.
• Energy constraints dictate that simple life stays small and simple:
  • Energy is generated at the cell membrane (through proton power).
  • Energy is then used inside the cell (to make proteins).
  • When a cell increases its size, its inside (volume) grows faster than it’s membrane (surface).
  • The cell’s larger inside translates into a larger energy requirement.
  • But, the surface area hasn’t grown enough to meet the increased energy demands.
  • So, it’s more efficient for the cell to stay small and simple.
• The emergence of complex life is therefore rare, here and elsewhere.
  • Complex cells have to escape the energy constraints of life by “combining”.
  • A combination of simple cells (one absorbs the other) is a rare event.
• A combined cell can break free of size and energy constraints.
  • The “swallowed” cell shrinks its genome and shed “unnecessary genes”.
  • The swallowed cell does one thing only: generate energy (mitochondria) for the host cell.
  • The host cell now receives new genes (from the swallowed cells) and has more energy (from the swallowed cell).
  • This allows the combined cell to grow in size and complexity.
• The cell-within-a-cell becomes the starting point for the evolution of complex life.
• The swallowed cells, mitochondria, drive much of what we care about:
  • Mitochondria contain the respiratory chain inside complex cells.
  • They drive the energy supply to cells (electron transfer and proton pooling).
• Much of life’s traits are about the match between a cell’s energy demand and its ability to generate energy:
  • How well do the mitochondrial and nuclear genome match.
  • Drives the formation of species, disease, ageing, fertility and (cell) death.

Worth Reading:

A challenging and dense read. The book is a long series of nuanced, logical arguments, attempting to fill in some of the biggest gaps in the history of life on earth. It does a great job combining insights from physics, chemistry and biology to formulate the most logical, be it sometimes speculative, explanations for specific historical developments. Its scope can be overwhelming as it tries trying to answer many fundamental questions at once, but you can’t fault it for swinging for the fences.

Most of the key arguments (about the origin of life, why simple life stays simple) seem convincing and rooted in empirical observations. I don’t know nearly enough about physics or chemistry to assess to what degree some of the book’s claims are as unavoidable as they are made out to be and the only logical explanations (is it rare for complex life to emerge, here or elsewhere? Is the way complex life on earth emerged to the only possible way?).

The evolution of the traits of complex life are explored through the application of mathematics, scenario analysis and simulations. Increasing computing power may provide more insights and could perhaps be used to explore and predict scenarios for the evolution of complex life going forward, rather than to explain its past.

Surprisingly, not much attention is given to network theory and the concepts of complexity and self-organization. It could perhaps have been applied to investigate the rarity of complex life (why is it such a rare event for simple cells to combine).

Practical Takeaways:

• Life is:
  • About the creation of order, structure.
    • Using biochemistry to resist the universal tendency to decay.
  • About the interaction between structure and its environment.
    • Seeking out structures that are the most comfortable state (lowering energy and entropy for the structure).
    • Most comfortable states give off heat to the environment (increasing the energy and entropy of the environment ).
  • All about electrons.
    • Life is nothing but an electron looking for a place to rest.
    • All of life involves the transfer of electrons down respiratory chains.
    • Electron donors and acceptors react slowly with each other and the flow of electrons generates energy.
  • All about protons.
    • The energy generated is captured and stored briefly in the form of (pools of) protons behind a membrane.
  • What happens in between…
• Universal process of energy generation, capture and usage:
  • Outside energy (food, sunlight) -> electron transfer energy -> proton gradient energy.
• Mitochondria are at the center of the evolution of the complex cell.
• Free radicals leaks fix problems: cells increase respiratory capacity or die (and get replaced, if possible).
  • Anti-oxidant supplements may suppress this mechanism.

Key Concepts:

Basic theories on the evolution of complex life.

• First, we thought it’s fusion: (endo)symbiosis.
  • Collaboration between two or more species, usually involving some sort of trade.
  • Some of the structures inside complex cells look and act like bacteria.
    • Mitochondria (converting food to energy).
    • Chloroplasts (converting solar power to energy in plants).
• Then, we thought it’s bifurcation: phylogenetics.
  • We explored the ancestry of genes to understand how species differentiated over time.
  • There was simply one fundamental gene that diverged over time into the three domains of life.
    • Bacteria (simple).
    • Archaea (simple).
    • Eukaryotes (complex).
• Now, we believe it’s both fusion + bifurcation:
  • Complex life arose from both fusion and bifurcation.
    • First fusion: in a rare endosymbisosis event, an archaeon host cell developed mitochondria and chloroplasts by absorbing bacteria.
    • Then bifurcation: all the other parts of complex cells then evolved by conventional means (natural selection).
• Questions:
  • Why did life evolve in this peculiar way?
  • Why did it evolve only once, or rarely?
  • What forces constrain bacteria and archaea – why do they remain simple?

The basic theory of energy generation inside cells.

• Flow of electrons and protons:
  • We gain energy from respiration: by ingesting food and oxygen.
    • Electrons flow from food to oxygen, generating energy (“redox chemistry”).
  • The electron energy generated is used to pump protons across a membrane, forming a pool of protons on one side (a “proton gradient”).
  • The energy is temporarily stored in the pool of protons sitting on one side of the membrane.
  • The flow of protons back across the membrane can be used to power cells (think of a turbine in a dam).
• This energy generation, storage and usage process (the use of proton gradients) is universal across all life on earth.
• Question:
  • Why are all cells powered in this peculiar way?

Central thesis:

• The origin of life was driven by a planet out of balance.
• This imbalance showed itself in local proton imbalances (proton gradients).
• These proton gradients drove the emergence of simple cells (the bacteria and archaea).
• Proton gradients were internalized by these cells and used as an internal power source.
• The limitations of internal proton gradients restricted the growth of bacteria and archaea, keeping them forever simple.
• In a rare, single event one bacterium got into an archaeon, breaking the energy constraints.
• The combined cell was able to evolve further and develop more complex traits.
• Energetic constraints make it possible to predict the most fundamental traits of life.

Evolution (natural selection) on its own is not sufficient to explain complex life.

• Evolutionary biology suggests life is about information transfer through genes.
  • Based on Schrodingers’s book: What is Life (1944)
    • Life somehow resists the universal tendency to decay (entropy, second law of thermodynamics).
    • The trick to life’s local evasion of entropy lies in the (information contained in the) genes.
• Suggests that there are no restrictions on varieties of complex life.
  • There is a huge variety of genes in terms of size and structure.
  • Would allow for unconstrained Information transfer.
• But, both history and past of complex life are poorly understood using only this framework.
  • Genes, environment and natural selection reflect the past, but can’t explain it.
  • None of these on their own can predict the future.

History of complex life suggests there are structural constraints to evolution.

• Life probably arose between 3.5 and 4 billion years ago.
  • Initially using photosynthesis as a form of energy.
    • Stripping electrons from a donor (iron, hydrogen sulphide or water).
    • Forcing the electron on to carbon dioxide.
    • Leaving behind waste products (rusty iron, sulphur, oxygen).
    • “Life is nothing but an electron looking for a place to rest”.
  • Earth atmosphere slowly accumulated oxygen and methane.
• Oxygen is the critical environmental determinant of life.
  • Oxygen permits the evolution of greater complexity.
    • Complex life requires a lot of energy.
    • Oxygen provides an order of magnitude more energy than other forms of respiration.
• So, with rising oxygen, we expect to see an explosion of life.
  • Expect many different forms of complex life emerging from simple bacteria and archaea.
  • Expect a mixed bag of internal structures, as complex cells evolve via natural selection.
• But, we don’t see this.
  • All eukaryotes basically have the same internal structure.
  • All eukaryotes seem to have a common ancestor.
  • This common ancestor seems to already have been quite complex.
• Suggests that there are structural constraints.
  • Kept bacteria and archaea simple (for 4 billion years).
  • On very rare occasions (maybe only once) allowed for a release from these constraints (through the emergence of one type of eukaryotes by endosymbiosis).

These structural constraints are rooted in how cells harvest energy.

• Life and living:
  • Life is about (maintenance of) order, structure.
  • Living is about the interaction between structure and its environment.
• Energy, entropy and structure (life).
  • You start with unordered parts (building blocks) and the influx of energy.
  • The influx of energy drives reactions among the parts to form ordered structures.
  • When an ordered structure is formed (say, a folding protein), it settles into its most comfortable, lowest energy state.
  • Because this form is the most comfortable and requires little energy, excess energy is released as heat into the environment.
  • The process of growth / structure / life:
    • Requires energy (to get parts to react).
    • Lowers entropy (as the ordered molecule is formed).
    • Releases energy (heat).
    • Increases entropy (as heat increases the entropy of the immediate environment).
• Universal biochemistry of life.
  • Form structure: lower energy, lower entropy.
  • Influence environment: higher energy (heat), higher entropy.
• Universal process of energy generation.
  • Outside energy (food, sunlight) -> electron transfer energy -> proton gradient energy.
  • Electron transfer energy (redox reaction):
    • Electrons are transferred from a donor to a receptor.
      • The donor is oxidized.
      • The receptor is reduced.
    • Respiration: all of life involves the transfer of electrons down respiratory chains.
    • Example: food (donor) + oxygen (receptor) = energy.
      • Food + oxygen provides energy to create ATP (out of ADP).
      • ATP splits into ADP and phosphate to provide heat energy to power cells.
      • Food + oxygen provides energy to reform ATP out of ADP, etc.
  • Proton gradient energy (proton-motive force, chemiosmotic coupling):
    • For each pair of electrons that passes through the respiratory chain, ten protons are pumped across the membrane.
    • Creates a proton gradient (the proton-motive force):
      • Different concentration of protons and electrical charge on either side of the membrane.
    • Example: in mitochondria, proton gradients drives the ATP synthase machinery (formation of ATP).
      • For every ten protons, you get three ATP molecules.
• Life is all about electrons and protons.
  • Electrons: electron donors and acceptors react slowly with each other and the flow of electrons generates energy.
  • Protons: capture and store energy briefly in the form of protons behind a membrane for later use.

Origins of life

• Living cells don’t need much energy to grow.
  • Enzymes inside cells channel and focus the reactions needed to grow.
  • Even then, living cells are wasteful, generating 40 grams of waste for every gram of biomass produced.
• Without the structure of the cell, you need the continuous influx of a lot of energy to get reactions started and keep them going.
  • Energy flux can create and sustain predictable physical structures (think: draining water in a plug hole).
  • It creates a stable, out-of-equilibrium state.
• What does it take to make a cell?
  • Continuous high flux of reactive carbon (building blocks).
  • Continuous supply of energy to drive the initial biochemistry.
  • Flowing past rudimentary catalysts that speed up and focus reactions.
  • The flow must be constrained / compartmentalized in some way (allowing for a build-up of end-products, organic matter).
  • Excretion of waste / heat to keep reactions going.
  • Hereditary material (make sure it happens again: replication, specify form and function).
• This process rules out the proverbial “primordial soup” as the origin of life.
• Hydrothermal vents are the ideal environment, bringing together rock, water and CO2:
  • • Warm, alkaline hydrothermal vents provide H2.
    • Formed by a chemical reaction between water and the mineral olivine (rock) below the ocean floor.
    • The warm hydrogen (H2) rich fluids that are formed slowly percolate up to the ocean floor.
    • Cool oceans contain high levels of CO2 (100-1,000 times greater than today).
    • Making the oceans acidic (pH of around 5-7, versus 8 today).
    • This environment cools down and accumulates the emerging H2.
    • Thin vent walls create relative differences in acidity on either side of the vent walls.
    • The difference in acidity creates different reaction potential between H2 and CO2.
    • The more acidic a solution, the easier it is to transfer electrons (ie, for redox chemistry to take place).
    • FeS (Iron Sulfide) minerals inside the vent walls allow for electrons to transfer from high alkaline to high acidity solutions.
• The reduction potential of this environment regulates the conditions under which life can evolve.
  • Resulting in the slow synthesis of organic molecules from H2 and CO2.
• By the rules of chemistry and geology, it is likely to find similar conditions (rock, water, CO2) for the emergence of life on most other planets.

Origins of simple cells

• How to find the last common universal ancestor (LUCA).
  • Trace how one species arose from another, assuming vertical inheritance.
    • Within species, parents pass copies of genes to their offspring by sexual reproduction.
    • Assumes that if you know the genotype, you can predict the phenotype.
• This is complicated by lateral gene transfer.
  • In bacteria, genes are passed on partially through lateral transfer, as well as wholly to daughter cells.
    • The rate of lateral gene transfer lowers the correlation between genotype and phenotype.
  • The consequence is that you can’t pinpoint one species of bacteria or archaea that is the most ancient.
• So what did LUCA look like?
  • Look at the universal genes present today in all bacteria and archaea (about 48).
  • These genes use biochemistry to power cells in a way similar to alkaline vent chemistry.
• How does organic matter develop at the vents.
  • Carbon fixation: the process of converting inorganic carbon (CO2) into organic molecules.
  • Takes places at the vents where organic molecules are formed and accumulate.
• Organic matter formed self-organizes into proto-cells.
  • Constant flux of carbon, energy, protons drives constant reactions.
  • Out-of-equilibrium systems generate initial semi-stable structures (similar to draining water in a bath-tub).
• These initial structures (proto-cells) make further organic matter.
  • By internalizing the vent’s biochemistry.
  • Using acetyl CoA pathway to make further organic matter.
    • Acetyl, a simple two-carbon molecule, is created from CO2.
    • Is combined with CoA (Coenzyme A) to form acetyl CoA.
    • Acetyl CoA is highly reactive and serves as the source of carbon for further growth.
• Proto-cells use proton power for energy.
  • Initially relying on the proton gradients inside the vents, as they flowed through the cell’s leaky membranes.
  • Over time, proto-cells developed internal proton pumps, making them rely less on naturally occurring external proton gradients.
  • Proto-cells can leave the vent and spread out across the oceans and rocks.
• Bacteria and archaea become different.
  • Developing different cell membranes and methods of (DNA) replication.
• By the rules of chemistry and geology, likely to find similar conditions for emergence of cells on most other planets.

Origins of complex cells.

• Early cells were and stayed simple.
  • They may have become metabolically versatile (much more so than most of complex life today).
  • But structurally they stayed very simple.
• Some answers on what constrained them unconvincing.
  • Cell walls too strong: strong walls are needed for structure, but prevent cells from changing shape or engulfing other cells.
  • Chromosomes were round: circular = slow, serial DNA replication restricts size (straight = fast, parallel DNA replication).
• Instead, the answer lies in how cells generate and store use energy:
  • Redox chemistry (shuttling around electrons) generates “some net energy” (maybe not enough to be used right away).
  • Chemiosmotic coupling (storing protons behind a wall) gives cells the ability to collect “loose change” and store energy (until there is enough of it to be used).
• This all takes place at the cell membrane.
  • This means that cell growth creates energy issues.
  • Cell volume (the inside of a cell where energy is needed to make proteins) grows faster than the cell membrane surface (where the energy is generated).
    • 80% of a cell’s weight is proteins.
    • Most of the energy costs of a cell relates to making and repairing proteins.
    • The more genes there are in a cell, the more proteins are made, the higher the energy demands.
  • So, energy per gene decreases when you get bigger, constraining cell size for simple cells.
• Only an endosymbiotic event can overcome this growth barrier.
  • Cells that were absorbed lost most of their original genes in order to survive and replicate fast.
  • Specifically, mitochondria lost almost all of their original genes (only 13 genes out of 4,000 remaining).
    • Mitochondria retained the genes needed for respiration, continuing to produce the same amount of ATP as before.
    • Mitochondria lost 99% of their genes, using much less energy (as they no longer had genes that ate up ATP to create other proteins).
    • The energy no longer needed by the mitochondria became available to the rest of the cell, spawning growth, new genes and new proteins.
    • The net energy saving were huge.
• Natural selection of simple cells does not lead to complex cells, except in extremely rare cases.
  • Today’s complex life derives its genes from a very specific group of bacteria (25) and archaea (7-8).
  • Points to a single time absorption of a bacteria by an archaeon.
  • Seems to be a rare, stochastic event.

Complex life, once established, evolved quickly

• As bacteria and archaea stayed simple, complex (eukaryotes) life evolved.
  • Bacteria show wide metabolic variety (they grow on anything).
  • And have biochemistry similar to eukaryotes (basic processes that keep them alive are similar: respiration, fermentation, photosynthesis).
  • But haven’t evolved, stayed small and simple.
• Likely that eukaryotes evolved quickly.
  • No (evidence of) stable intermediaries.
  • All eukaryotes share a huge portion of common complex traits.
  • Points to sexual reproduction of a small unstable population over a brief period of time.
• The evolution of complex life was driven by the structure of its genes.
  • The cell nucleus had to evolve in order to separate DNA transcription (slow) from DNA translation (fast).
    • Inside the nucleus, genes are spliced, “cleaned up” and transcribed into RNA.
    • Outside the nucleus, the cleaned up RNA is then translated into proteins.
    • Without a barrier, ribosomes would quickly translate non-cleaned up RNA and create useless proteins.
  • Sex had to evolve to promote maximum variance of genes.
    • Sex involved reciprocal recombination across the entire genome.
    • Breaks up rigid combinations of genes.
    • Allows natural selection to see and parse individual genes.
    • Maintains variation in a population and allows for adaptation to changing environments.
    • Without this, damaging mutations may accumulate and the loss of variation may make populations vulnerable to extinction.
  • Similarly, two sexes (mating types) and the immortal germ line had to evolve to cope with the increasing complexity of cells.

The importance of mitochondria in the evolution of complex life

• Mitochondria:
  • Mitochondria are the the assembly lines of proteins that carry electrons from food to oxygen (the respiratory chain).
  • They started as bacteria cells invading host cells.
  • Today, mitochondria are an integral part of the cell nucleus.
  • The development of mitochondrial function depends on two distinct genomes.
    • One inside the mitochondria.
    • One inside the host cell nucleus.
  • While these two genomes diverge continually …
    • The two genomes evolve at different speeds.
    • Mitochondrial genes evolve 10-50x faster than the genes in the nucleus.
  • …. they need to work together closely …
    • Together they code all of the structural proteins making up the mitochondria.
    • If the structure of the mitochondria is off by the slightest margin, the respiratory chain collapses.
  • … so they need to co-evolve and co-adapt through natural selection …
    • As mitochondria evolved, they transferred almost all of their genes (except 13) to the cell nucleus.
    • Each time the mitochondria shrank its genome, it resulted in the formation of new combinations of mitochondria and nucleus genomes.
    • If these new combinations of mitochondria and nucleus genomes worked well:
      • Generated ATP more efficiently.
      • Allowed for life to use the extra energy to evolve and become more complex.
    • If these new two genomes did not work well together:
      • Cell death (apoptosis) was triggered:
        • The electron transfer would slow down and electrons got stuck in the respiratory chain (in the various redox centres).
        • The accumulated electrons would generate an excess of free radicals (as iron-sulphur clusters react with oxygen).
        • The excess free radicals would cause the separation of cytochrome c.
        • Without cytochrome c, electrons can no longer reach oxygen and the respiratory chain collapses.
        • Without electron flow, no proton pumping: collapse of the membrane (electrical) potential.
        • This chain of events triggers programmed cell death, or apoptosis.
        • An army of proteins cuts the cell into pieces, which are fed to surrounding cells.
  • This co-adaptation process drove the formation of species …
    • • The mitochondrial genes of separate populations change fast and diverge over time.
      • Mitochondrial genes in one population may no longer be compatible with the nuclear genomes of the other.
      • Paring is no longer possible (off-spring does not survive).
  • … and drives the trade-off between fitness and fertility, ageing, death …
    • Different organisms / cells have different metabolic thresholds depending on:
      • The metabolic demands required to accomplish the task.
      • The metabolic power available.
    • A high metabolic demand (think: a pigeon that needs to fly):
      • Low threshold for mismatch between mito and nuclear genomes.
        • Cell death is triggered more easily when the (high) metabolic demands of cells are not met.
        • This has costs: early cell death results in low fertility and there is less tolerance for gene variation (=poor adaptability).
        • And benefits: a high aerobic fitness and lower risk of diseases (less free radical creation), slower ageing.
      • A low metabolic demand (think: a rat):
        • High threshold for genome mismatch.
          • Cells don’t die as easily, as they have lower metabolic demands (and can handle more free radical leaks).
          • Costs: low aerobic fitness, higher risk of disease, faster ageing.
          • Benefits: higher fertility, higher tolerance for gene variation (=better adaptability to environment).
        • Explains difference in life span: pigeons (30+ years) vs. rats (3-4 years).
        • Selection for greater aerobic capacity (and therefor, a more efficient respiratory chain) over generations should prolong lifespan (at the cost of lower fertility).
  • The nuanced version of the free radical theory of ageing: free radical signaling and apoptosis.
    • Early theories about free radical were incorrect.
      • Thought that free radicals are bad, so fight them with anti-oxidants.
      • But, anti-oxidant supplements didn’t prolong life.
    • Free radicals are needed to optimize respiration (signaling, apoptosis).
      • Excess free radicals form when the respiratory capacity of a cell is too low.
      • They signal for higher respiratory capacity:
        • Increase respiratory capacity by making more mitochondria (mitochondrial biogenesis.)
      • If that doesn’t work, they kill the cell (apoptosis):
        • If that doesn’t fix the problem, kill the cell.
        • Activate stem cell to create a new cell.
      • Anti-oxidant supplements may suppress this mechanism.
    • There is no simple relationship between the rate of “living” and degree of free radical leak.
      • For instance, free radical leaks during exercise is not higher (which you expect, because you consume more energy), but lower (because the electron flux increases).
  • Energy deficiencies caused by genomic mismatching drive ageing and lifespan.
    • Genomic mismatches accumulate with age.
    • Undermine mitochondrial performance.
    • Free radicals leaks try to fix the problem: cells increase respiratory capacity or die.
    • If cells die and aren’t replaced, the tissue loses mass.
    • Fewer cells remain to do the same job, causing more stress, more mutations (sometimes cancer), more genomic mismatches -> cycle continues.
  • What can you do:
    • Exercise, calorie restriction and low-carbohydrate diet.
    • All promote physiological stress response that clear out bad mitochondria.