Literary Insights

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Here is a summary of the key points from the introduction of Power, Sex, Suicide: Mitochondria and the Meaning of Life by Nick Lane:

Mitochondria are organelles found in the cells of eukaryotic organisms that generate most of the cell’s supply of adenosine triphosphate (ATP), used as an energy source.
Mitochondria originated as independent bacteria engulfed by early eukaryotic cells over a billion years ago. This critical event allowed for the evolution of advanced multicellular life.
Mitochondria have their DNA, separate from the nucleus, and are passed down solely through the mother’s egg cell. This matrilineal inheritance has implications for human evolution and prehistory.
Mitochondrial dysfunction has been linked to aging and many diseases. The “mitochondrial theory of aging” proposes that damage to mitochondria over time is a significant cause of aging.
The book explores the profound impact mitochondria have had on life’s major transitions, from the initial origin of complex cells to the evolution of advanced physiology, multicellularity, sex/gender, and aging/death. Mitochondria hold the key to understanding these fundamental aspects of life.

In summary, the introduction frames mitochondria as clandestine rulers that have profoundly shaped life’s trajectory over billions of years of evolution according to the author’s thesis in the book.

Mitochondria are tiny organelles inside cells that generate most of the cell’s energy through ATP production via oxygen-based respiration. Each cell contains hundreds to thousands of mitochondria.
Mitochondria were once free-living bacteria that adapted to live inside larger cells billions of years ago. They retain some of their genes.
Tracing inheritance through mitochondrial DNA led to the theory of “Mitochondrial Eve,” the most recent common maternal ancestor of all living humans.
Mitochondrial DNA is helpful for forensic identification and matching relatives due to its abundance and maternal inheritance pattern.
The “mitochondrial theory of aging” suggests damage to mitochondria and mitochondrial DNA from free radicals contributes to aging and age-related diseases.
Certain inherited mitochondrial diseases affect metabolically active tissues and progress with age.
Controversial “ooplasmic transfer” fertility treatments involve transferring mitochondria between egg cells.
Mitochondria were inaccurately referenced in a Star Wars movie to explain the Force through reference to “midichlorians”.
Mitochondria are considered the powerhouses of cells that generate energy. Their bacterial ancestry is well accepted today, with mitochondria believed to have originally been free-living bacteria engulfed by early eukaryotic cells.
Mitochondria play an essential role in programmed cell death (apoptosis), critical for multicellular organisms. Cancer occurs when cells fail to undergo apoptosis. Researchers are now targeting mitochondria to manipulate apoptosis.
Mitochondria were critical for the evolution of multicellular organisms because they enabled the emergence of programmed cell death. This allowed cells to sacrifice themselves for the greater organism. Without this, multicellular life may not have evolved.
Mitochondria were also integral to the origin of the first eukaryotic cells. Now it appears complex life could not have evolved without mitochondria - they were essential for the emergence of multicellular organisms and eukaryotic cells.
Mitochondria also help explain sex and the need for two sexes. Their role in mitochondrial inheritance through maternal egg cells vs paternal sperm cells provides insight into this evolutionary puzzle.
Despite their importance, mitochondria remain an “enigma” with many deep evolutionary questions poorly understood. The article discusses exploring these questions further.

Here is a summary of the key points about the method of Sherlock Holmes as they relate to reconstructing the evolution of life:

Holmes advocated eliminating the impossible to arrive at the truth, however improbable it may seem. While one cannot eliminate possibilities in development, reconstructing the most likely evolutionary paths based on available evidence follows a similar slothful approach.
The author hopes to convey some of their excitement about reconstructing evolution to the reader, just as Holmes enjoyed the challenge of the investigation.
Understanding cell biology provides essential context for unraveling evolution, as cells are the basic units of life. Bacteria represent the simplest cell type, while eukaryotic cells like those in humans are much more complex.
Key components of cells like DNA, RNA, proteins, membranes, and organelles must be accounted for in reconstructing evolution. The relationships and functions of these components provide clues about evolutionary ancestry and mechanisms.
By carefully examining the evidence available across domains of life, from structural and functional similarities to the organization of genes and molecules, one can work to distinguish the probable from the improbable in the sequence of evolutionary events, just as Holmes pieced together clues to identify the truth.
Cells contain specialized proteins called transcription factors that regulate gene expression. When a gene is expressed, it is converted from dormant code into an active protein that performs functions in the cell.
Mitochondria are organelles inside cells that are dedicated to energy production. They were once independent bacteria but now exist inside cells. Mitochondria have two surrounding membranes and inner convoluted folds called cristae, where respiration occurs.
Early researchers like Altmann proposed that mitochondria were independently living organisms that came together in cells for mutual benefit. This endosymbiotic theory proposed mitochondria as modified bacteria living inside cells.
Later, researchers like Portier and Wallin tried to culture mitochondria to demonstrate their bacterial nature but failed, so the endosymbiotic theory was rejected.
In 1967, Lynn Margulis resurrected the endosymbiotic theory, providing more robust evidence from mitochondrial DNA/RNA and examples of “cytoplasmic heredity.” She viewed mitochondria evolution through a broader geological and atmospheric lens. This supported mitochondria originating as independent bacteria that formed symbiotic relationships inside cells.
Lynn Margulis proposed the endosymbiotic theory that eukaryotic cells evolved by merging and incorporating ancestral bacteria. She argued mitochondria and chloroplasts originated this way.
Many journals and publishers initially rejected her work. It took convincing evidence like DNA sequencing to gain widespread acceptance. Debates persisted for over a decade as alternative explanations were proposed.
Mitochondria possess several bacterial-like features like circular DNA, lack of histones, protein assembly processes, and susceptibility to some antibiotics. This supported their endosymbiotic origin but could also be explained as retaining ancient traits without evolution.
Sequencing showed mitochondrial genes evolve faster than nuclear genes, supporting bacterial ancestry rather than just retention of ancient traits. This and comparisons to proteobacteria provided strong evidence for the endosymbiotic theory regarding mitochondria.
While widely accepted for mitochondria, Margulis argued eukaryotic cells evolved through multiple mergers, not just one. Others argue cooperation raises competition between more complex resulting organisms.
The universal presence of mitochondria in all eukaryotes suggests their acquisition was pivotal to eukaryotic evolution. Newly discovered small eukaryotes in extreme environments also possess mitochondria, supporting this.

Here are the critical points about mitochondria from the passage:

Mitochondria were originally a separate single-celled organism that was engulfed by a larger cell, in a rare event that led to the formation of the first eukaryotic cell around 2 billion years ago.
This merging of cells was crucial to the evolution of complex multicellular life, as all such life is made of eukaryotic cells containing mitochondria.
Mitochondria became a crucial part of cells, generating most of the cell’s supply of ATP (energy). They are considered the “powerhouses of the cell.”
Their original bacterial ancestry is still evident from their DNA, which is separate from the primary nuclear DNA of the cell.
Mitochondria play a central role in cellular energy production and power all biological processes like growth, cell division, movement, and signaling. They are the ‘clandestine rulers’ that drive life.
The passage frames mitochondria as responsible for biological characteristics like power, sex, and even suicide at the cellular level due to their influence over energy production and apoptosis (programmed cell death).
There is a huge evolutionary gap between bacteria and eukaryotic cells. Bacteria dominated for 2 billion years but never evolved past basic multicellularity. Eukaryotes emerged later and rapidly gave rise to complex life.
Some argue the origin of eukaryotes was a inevitable “bottleneck” caused by sudden environmental changes like rising oxygen levels. One proto-eukaryote happened to be better adapted and prospered while others died out.
However, the author finds this bottleneck theory unconvincing. The world did not change uniformly and many varied niche environments persisted. Both oxygenated and anoxic (without oxygen) territories continued to exist. Surviving in these different environments requires very different biological skills.
The sheer diversity of life weighs against a single monolithic bottleneck event. The evolution of eukaryotes has been genuinely contingent and unpredictable, not an inevitable consequence of environmental changes alone. Their origin involved unique molecular innovations like the nucleus and mitochondria.

In summary, the author argues the emergence of eukaryotic cells was an unlikely evolutionary leap, not just an adaptation to environmental changes through a bottleneck, given the persistence of varied environments and the diversity that evolved from eukaryotes.

Bacteria and eukaryotes differ dramatically, with most eukaryotic cells being 10-100 times larger than bacteria.
Eukaryotes possess a membrane-bound nucleus containing DNA, which bacteria generally lack or have only a primitive version. This is a major defining characteristic of eukaryotes.
Eukaryotic genomes are much larger than bacterial genomes, containing many more genes and total DNA (C-value). Even simple single-celled eukaryotes like yeast have several times as many genes as most bacteria.
The fusion of two whole genomes - a bacterial cell and archaeal cell - to create the first eukaryotic cell with a nucleus can be viewed as a “macro-mutation”, a rare and improbable event, rather than gradual evolution via small changes alone. This created what Goldschmidt termed a “hopeful monster”.
The differences between bacteria and eukaryotes span multiple levels including size, genome/DNA content, and subcellular structures, representing a significant evolutionary divergence or “chasm”. The origin of the eukaryotic cell was thus an unlikely and monumental event.
Eukaryotic cells contain much more non-coding DNA than prokaryotic cells like bacteria. The total DNA content of eukaryotes spans five orders of magnitude, from 200,000 times larger to 200 times smaller than humans.
This massive variation in DNA content, known as the C-value paradox, is unrelated to organism complexity or gene number. An amoeba may have more DNA but fewer genes than humans. The purpose of much of the non-coding DNA is debated.
Eukaryotic DNA is organized differently - it is contained in linear chromosomes inside the nucleus, while bacteria usually have a single circular chromosome. Eukaryotic genes are also randomly ordered and often fragmented.
Besides DNA differences, eukaryotic cells contain internal membrane structures like the endoplasmic reticulum and golgi apparatus that compartmentalize the cell. They also have organelles like mitochondria and chloroplasts derived from ancient bacterial endosymbiosis.
Eukaryotic cells lack a rigid cell wall and instead have a flexible membrane stabilized by an internal cytoskeleton, allowing more dynamism than the static cell walls of bacteria.
Eukaryotic cells differ significantly from bacteria in size, internal structures like the nucleus and organelles, genetic material, and reproduction methods.
Two main hypotheses attempt to explain the evolution of eukaryotes: 1) numerous mergers between bacterial cells, and 2) most eukaryotic features evolving independently without bacterial mergers.
The mainstream view is that eukaryotes evolved gradually from bacteria through several small steps. A critical stage was the catastrophic loss of the bacterial cell wall, which forced adaptation.
Losing the cell wall provided advantages like changing shape and engulfing food through phagocytosis, distinguishing eukaryotes from bacteria.
It was thought bacteria lacked an internal cytoskeleton, so eukaryotes must have rapidly evolved their complex skeleton. But some bacteria have a cytoskeleton of protein filaments providing structural support, similar to eukaryotes.
This challenges the view that few bacteria can survive without a cell wall and questions why bacteria with cytoskeletons don’t survive wall loss more readily. More evidence is needed to understand the transition from bacteria to eukaryotes.

Here is a summary of part 3:

The Archaea were discovered in 1977 and found to have unique traits not seen in bacteria, justifying classifying them as a separate domain of life along with bacteria and eukaryotes.
Archaea share some traits with bacteria and eukaryotes, having a “mosaic” of characteristics. For example, their ribosomes and DNA transcription processes are more similar to eukaryotes.
This supports the idea that archaea were a “missing link” between bacteria and eukaryotes, with eukaryotes possibly descending from archaea-like ancestors.
Some single-celled eukaryotes called archezoa lack mitochondria. Cavalier-Smith proposed in 1983 that at least some archezoa were “primitively amitochondriate”, never having mitochondria and resembling early eukaryotes.
Comparing gene sequences between organisms can reveal how closely related they are in evolution. Testing Cavalier-Smith’s hypothesis involved sequencing archezoan genes to see if they resembled ancient eukaryotes.
Four primitive eukaryotes lacking mitochondria and organelles were confirmed by genetic analysis to be among the earliest eukaryotes, supporting Cavalier-Smith’s hypothesis. The first was the microsporidium V. necatrix.
Microsporidia are intracellular parasites that infect a wide range of eukaryotic cells. While they lack mitochondria and organelles, their diverse hosts suggest ancient origins.
Three other primitive eukaryote groups were later confirmed as ancient: archamoebae, metamonads, and parabasalia. These include pathogens that cause diseases in humans.
Mitochondria are thought to have originated when a eukaryotic cell engulfed but did not digest an aerobic bacterium around 2 billion years ago, as oxygen levels rose.
The initial relationship may have been parasitic or mutualistic. Over time, the host came to tap the bacterium’s energy-generating abilities and became enslaved as the modern mitochondrion.
Rising oxygen levels could have initially benefited the aerobic bacterium by protecting the anaerobic host from oxidative damage, per the “Ox-Tox” hypothesis.
This eventual engulfment and integration of an aerobic proteobacterium are believed to have given rise to the familiar eukaryotic cells with mitochondria.
Originally, it was widely believed that the earliest eukaryotic cells (archezoa) never had mitochondria and evolved through a gradual series of steps involving rising oxygen levels.
However, in the late 1990s, this idea collapsed as new evidence emerged. When more archezoan genes were sequenced, it appeared they had traces of once having mitochondria.
Further studies found that all supposedly primitive archezoans tested had mitochondria or once. This suggested the mitochondrial merger occurred very early in eukaryotic evolution.
Comparing eukaryotic, archaeal, and bacterial genes revealed that eukaryotes’ informational genes were most similar to methanogenic archaea. Structural similarities between eukaryotic and methanogen histones also pointed to a common ancestor.
This evidence supports the idea that the original host in the merger that created the first eukaryotic cell was a methanogenic archaeon, rather than a primitive phagotrophic cell as previously believed. The archezoan hypothesis was discovered to be incorrect.

So in summary, new evidence overturned the established ideas about eukaryotic origins, showing that all eukaryotes had mitochondria early on and suggesting the progenitor was a methanogenic archaeon, not a primitive archezoan. This was a significant reversal in the field’s understanding.

The origin of the eukaryotic cell is thought to have involved an endosymbiotic relationship between two prokaryotic cells - a host and mitochondrial ancestor.
Prior hypotheses proposed the host was an oxygen-fermenting cell and the symbiont allowed oxygen respiration. But methanogens, whichrequire anoxic conditions, are most closely related to eukaryotes genetically.
Bill Martin proposed the “hydrogen hypothesis” - that the symbiont was related to mitochondria and hydrogenosomes, organelles producing hydrogen gas as a byproduct.
Hydrogenosomes are found in primitive eukaryotes and share a common ancestor with mitochondria. Their original ancestor must have been able to perform both oxygen respiration and hydrogen production.
The key idea is that hydrogen gas, not oxygen, was necessary for the symbiosis. The hydrogen-producing symbiont could have benefited the methanogenic host by providing an alternate energy source in the form of hydrogen.
This addresses the paradox of how a strictly anoxic methanogen could form a symbiosis with an oxygen-dependent organism under prior hypotheses focused on oxygen.
Martin and Müller observed that eukaryotic cells containing hydrogenosomes (organelles that produce hydrogen gas) are sometimes hosted by methanogenic archaea inside the cell.
The archaea align themselves with the hydrogenosomes, appearing to “feed” off them.
Martin and Müller realized the archaea were feeding on the hydrogen gas and carbon dioxide released by the hydrogenosomes, using these to generate all their organic molecules and energy through methanogenesis.
This intimate metabolic relationship, with the hydrogenosomes providing nutrients for the archaea, was proposed as the basis for the original endosymbiotic merger that gave rise to the first eukaryotic cell.
The hydrogen metabolism of the hydrogenosome-containing bacterium, providing hydrogen to feed the archaea, gave the early eukaryote its evolutionary advantage - not its oxygen metabolism, as oxygen levels were still low on Earth then.
The hydrogen hypothesis proposes that the earliest eukaryotic cell arose from an endosymbiotic relationship between an archaean methanogen and a bacteria. This could explain various evolutionary puzzles surrounding the origin of eukaryotes.
Some key questions the hypothesis addresses are: Why did oxygen-respiring genes not disappear from the earliest eukaryote if it lived anaerobically? And how did the bacterium initially gain entrance into the archaean host cell without the need for phagocytosis?
The narrative describes how metabolic cooperation and gradual physical engulfment of the bacterium by the archaean could have led to increasing codependence and eventual gene transfer, allowing the host to take up various metabolic functions from the bacterium.
This chain of events is presented as a plausible yet contingent scenario that capitalized on environmental conditions at the time but may not necessarily repeat itself. The evolution of the eukaryotic cell is considered a unique chance event.
While speculative, the hydrogen hypothesis provides a coherent potential explanation for the early evolution of eukaryotes without requiring major innovations - just incremental changes driven by natural selection and population dynamics.
Early methanogens would have blocked their only energy source (methane production) if oxygen levels rose. Internalized alpha-proteobacteria could use oxygen more efficiently, benefiting both cells.
The host cell needed an ATP pump to drain energy from the proteobacteria guest, allowing symbiosis. ATP pumps evolved early in eukaryotes.
Gene transfer gradually led to chemical dependency developing into a single chimera cell with mitochondria-like organelles. This prototype eukaryote was able to import and ferment sugars.
Chance played a role, but rising oxygen and sulfate levels may have favored the transition to an aerobic lifestyle before genes for oxygen respiration were lost. Competition from sulfate-reducing bacteria could have forced the move to oxygenated surface waters.
The mitochondrial energy generation mechanism across a membrane gave eukaryotes an advantage allowing their complex lifestyles. It may also explain the origin of life utilizing proton gradients.

This passage discusses the fundamental role of energy in sustaining life. It introduces Peter Mitchell and his Nobel Prize-winning work elucidating how cells generate energy through chemiosmosis and the proton-motive Force.

Mitchell articulated a fundamental biological insight about how cells convert energy in their mitochondria. His ideas challenged previous theories in a way comparable to major physics revolutions. However, Mitchell worked in relative obscurity compared to DNA pioneers Watson and Crick.

The passage argues that while genetics receives substantial attention, bioenergetics - the study of energy generation in organisms - is comparatively overlooked. Yet energy production is essential for cellular functions and constrains biological evolution. Understanding Mitchell’s insights into cellular energy mechanisms is necessary for explaining critical aspects of life like the evolution of complex cells, sex, aging, and more.

The passage explains later how mitochondria enabled the evolution of complex life by providing eukaryotic cells with unprecedented energy production capabilities while imposing constraints that shaped development in specific ways. This historical perspective aims to appreciate the great minds who advanced our understanding of the vital role of energy in sustaining life.

Antoine Lavoisier argued in the 18th century that respiration is a form of combustion or oxidation. He said it is the slow combustion of carbon and hydrogen in the blood, similar to a burning candle.
Lavoisier was correct that respiration extracts carbon and hydrogen from foods like glucose, but he died in the French Revolution before further discoveries.
It was later determined that respiration occurs in cells, not the blood, and takes place within organelles called mitochondria.
Respiration is an electrochemical redox reaction where oxygen oxidizes compounds like glucose, extracting electrons. This releases energy that cells can harness to do work.
Understanding energy and thermodynamics in the 19th century helped explain that respiration releases potential energy from fuel bonds, and this energy powers biological processes and drives muscle contraction.
Early scientists searched for tissue pigments that might catalyze respiration like hemoglobin does in blood. 1884, Charles MacMunn discovered one such dye but could not characterize it. In 1925, David Keilin rediscovered and began studying this pigment.

So, in summary, it traces the critical discoveries around understanding respiration as a cellular redox process and the search for pigments in catalyzing it within cells.

David Keilin went beyond MacMunn’s early observations of complex absorption spectra in cells and showed it was attributable to three pigments, which he named cytochromes a, b, and c. This helped explain the spectra.
However, none of Keilin’s cytochromes directly reacted with oxygen. Otto Warburg further elucidated the “missing link” through indirect carbon monoxide binding experiments. He determined the absorption spectrum of the “respiratory ferment”.
Warburg’s work suggested respiration evolved before photosynthesis. Keilin developed the idea of the respiratory chain, where protons and electrons from glucose breakdown are passed from one cytochrome to the next like buckets, releasing energy in small steps.
Despite advances, the complete picture of how respiration worked remained unclear. Keilin’s concept of the respiratory chain involving linked redox reactions was later supported by Warburg’s discovery of additional non-protein components, or coenzymes.
Today, we understand respiration involves four complexes along the mitochondrial inner membrane comprising the electron transport chain, passing electrons from glucose down to oxygen to form water. But how this was coupled to ATP synthesis was still unknown.

So, in summary, it outlines the fundamental discoveries and evolving understanding of the components and process of cellular respiration, culminating in the realization that an intermediate must exist to store energy from the electron transport chain and fuel ATP synthesis, though its identity was still unknown.

Here is a summary of the key points about proton power and the origin of life from the passage:

ATP (adenosine triphosphate) was discovered in 1929 and shown to be the universal energy currency of life. It is produced by respiration, fermentation, and photosynthesis.
Respiration generates significantly more ATP per molecule of glucose than fermentation. Respiration produces around 19 times more ATP.
ATP works like a rechargeable battery. When its terminal phosphate is removed, energy is released that can power cellular work. It must continuously be regenerated from ADP + phosphate, which requires energy input.
Fermentation and respiration both serve to produce ATP, with fermentation acting as an backup energy source when oxygen levels are low.
The discover of ATP explained how energy is conserved and distributed within cells from energy-generating processes like respiration and fermentation.
While ATP is often depicted as having a “high-energy bond,” the disequilibrium between ATP and ADP concentrations in the cell, with far more ATP, represents the stored potential energy rather than anything unusual about ATP’s bonds.

So, in summary, ATP was identified as the critical molecule that couples energy production via respiration and fermentation to energy-dependent cellular work, representing a crucial step in understanding energy flow in living systems.

Hydroelectric schemes work by pumping water up to a high reservoir at night when electricity demand is low. The water is then released during periods of high demand, such as after popular TV shows when many people put on kettles for tea.
In cells, ADP is continually pumped to generate a reservoir of potential energy in ATP. This ATP reservoir then powers various cellular tasks, similar to how stored water powers electricity generation.
Producing high levels of ATP requires energy, just as pumping water uphill involves energy. Cellular respiration and fermentation provide this energy.
Efraim Racker discovered that fermentation uses the energy from breaking down sugars to attach phosphate groups to fragments, against equilibrium, generating ATP. A similar coupled process was presumed to drive ATP formation in respiration.
However, the mechanisms of respiration posed challenges. Respiratory complexes are separated from ATP synthase complexes, yet they must communicate. Attempts to identify a hypothetical “high-energy intermediate” between them spanned decades unsuccessfully.
The number of ATPs produced per electron transferred is variable and non-integer, conflicting with chemistry. Membrane integrity is also crucial, yet uncoupling agents share no common mechanism - conventional chemistry could not fully explain respiration.
In 1961, Peter Mitchell proposed his controversial proton-motive force hypothesis to explain respiration, sparking decades of research and resolving the outstanding issues.
Peter Mitchell hypothesized that active transport of molecules across cell membranes uses energy from respiration via chemiosmosis, or the creation of a proton gradient across the membrane.
During respiration in mitochondria, the electron transport chain pumps protons out of the mitochondrial matrix and into the intermembrane space, creating a proton gradient.
This proton gradient constitutes the “proton-motive force, ” with an electrical and pH component. The Force acts to drive protons back into the matrix.
Mitchell proposed this proton-motive Force is harnessed by ATP synthase to drive the phosphorylation of ADP to ATP, without the need for a hypothetical “high-energy intermediate”.
Pumping protons in one area of the membrane generates a force that can drive reactions anywhere along the membrane surface.
Uncoupling agents disrupt respiration by shuttling protons back across the membrane, dissipating the proton gradient, and uncoupling ATP production from glucose oxidation.
Mitchell’s hypothesis elegantly explained many outstanding questions about respiration and membrane transport but was initially met with skepticism from the scientific establishment.
Respiration, photosynthesis, and bacterial energy generation all work via proton pumping across a membrane. Redox reactions release energy to pump protons, generating a proton-motive force (PMF).
The PMF acts as an “intermediate reservoir” of stored energy. It consists of a pH gradient and an electrical charge across the membrane.
The PMF drives ATP synthesis by the ATP synthase enzyme. As protons flow back through the synthase, it acts as a rotary motor to generate ATP from ADP and phosphate.
Mitchell’s chemiosmotic theory explained how a non-integer number of electrons can generate ATP. It also made testable predictions that were confirmed experimentally over the following years.
Experiments by Jagendorf and Uribe showed that a pH gradient alone could drive ATP synthesis in chloroplasts, providing strong evidence for chemiosmosis.
Beyond ATP synthesis, the PMF is a general “force field” that allows bacteria to harness energy for other functions like active transport across membranes.

In summary, proton pumping and the PMF it generates is a fundamental and nearly universal mechanism by which cells store and utilize energy from redox reactions.

The origin of life is challenging to explain because DNA needs proteins to evolve but proteins need DNA to evolve.
Many scientists propose an “RNA world” where RNA could self-replicate and form early life before being replaced by DNA/proteins. However, RNA is a limited catalyst and energy source for replication needs to be clarified.

Based on Miller-Urey experiments, An abiotic “primordial soup” of organic molecules was suggested as fuel for early replication. However, early atmosphere composition is disputed.

A constant energy input was needed to drive RNA replication and overcome instability. Possible sources included meteor impacts, volcanism, lightning, hydrothermal vents.
Chemiosmosis may provide the most sensible mechanism to convert various energy sources into a usable form for early life. Proton gradients could fuel replication before complex biochemical pathways evolved.
Maintaining a proton gradient is fundamental to life and may be tied to the very origin of life from natural proton forces on early Earth.
Fermentation was proposed as an early source of energy for life on Earth, but there are problems with this idea. Fermentation does not involve pumping protons across a membrane like respiration and photosynthesis.
If fermentation was the sole early energy source, the supply of fermentable organic molecules from asteroids should have run out long before complex life evolved. Photosynthesis took a long time to develop after life began.
Fermentation requires a complex set of enzymes and is not as straightforward or primitive as once thought. It may have been “irreducibly complex” and initially needed an energy source to evolve.
Evidence suggests LUCA (Last Universal Common Ancestor) did not ferment as modern organisms do, using different enzymes. This implies fermentation evolved later, independently in bacteria and archaea.
Respiration via proton pumping is a more straightforward and universal trait bacteria and archaea share. It may have evolved early in LUCA before the divergence of these domains.
However, modern cell membranes pose problems for early evolution. Bacteria and archaea have dramatically different membrane compositions and lipid architectures, implying very early divergence before complex membranes evolved.

So, in summary, the passage casts doubt on fermentation as the original energy source and favors some early forms of respiration utilizing simpler membranes than modern cells. However, incorporating membrane evolution poses challenging problems for theories of life’s origin.

Martin and Russell concluded that LUCA (the last universal common ancestor) could not have had a lipid membrane, as lipids are too complex. LUCA must have had some membrane to facilitate chemiosmosis (proton pumping).
They proposed LUCA may have had an inorganic membrane made of iron-sulfur minerals, forming a “thin, bubbly layer” enclosing early organic molecules.
Iron-sulfur minerals were able to catalyze early organic reactions, possibly leading to an “RNA world” where natural selection took over.
Black smokers prove that iron-sulfur minerals can catalyze reactions and support life independently of sunlight. However, the dilution problem limits responses to mineral surfaces.
Russell proposed smaller volcanic seep sites could have formed primitive protocells bounded by iron-sulfide membranes through the hydrothermal fluids and ocean waters mixing. Laboratory experiments successfully recreated these conditions.
The iron-sulfide membranes were naturally chemiosmotic and could conduct electrons, providing a proton gradient to drive ATP synthesis without complex metabolic pathways. This favors their role in the origin of life.
Conditions for forming many such protocells were likely joint on the early Earth, making their emergence probable. Russell argues this could have marked the transition to life itself.
Bacteria dominated life on Earth for over 2 billion years but never evolved greater complexity, staying as single-celled organisms. Complex multicellular life only emerged after the evolution of eukaryotic cells.
Eukaryotic cells were formed via the endosymbiotic union of an archaeon and bacterium. This allowed energy generation to be internalized in mitochondria.
Why did bacteria never internalize their energy generation? The answer lies in the persistence of mitochondrial DNA over billions of years.
Mitochondria played a crucial role in seeding complexity. Once they existed within cells, life was “almost bound” to become more complex over evolutionary timescales.
Natural selection acts as a ratchet, taking random genetic variations and turning them into trajectories of increasing complexity and refinement of biological functions over generations.
Greater complexity requires more genes. These can arise through gene duplications, whole genome duplications, or unions of genetic material from multiple organisms. Small mutations alone are not sufficient to drive significant increases in complexity.

In summary, the emergence of eukaryotes and mitochondrial energy generation played a pivotal role in allowing and driving the evolution of multicellular complexity on Earth.

The evolution of genomes and the spread of repetitive DNA sequences are not strictly Darwinian processes, as they involve significant, dramatic changes in total DNA content via mechanisms like endosymbiosis. However, except for these “giant leaps”, the subsequent processes of natural selection on new genes are Darwinian.
While bacteria have achieved immense biochemical diversity, they have failed to develop significant morphological complexity over billions of years. On the other hand, Eukaryotes have shown a “ramp of complexity” with features like organelles, nuclei, multicellularity, differentiation, and sensory organs in just half the time.
The divide between simple bacteria and complex eukaryotes can only be bridged by endosymbiotic processes like forming mitochondria via a merger between bacterial cells. Without this merger, it is argued the complex biochemistry required for eukaryotic cells would not have evolved.
While symbiosis is part of standard evolution, some significant novelties like the genesis of eukaryotes required symbiotic mergers that could not have occurred through gradual natural selection alone. Mitochondria in particular were necessary to pave the way for increased complexity in life.
It is next to impossible for eukaryotes to evolve from prokaryotes via natural selection, given the mechanism of chemiosmotic energy production (discussed in Part 2). Chemiosmosis places eukaryotes at the beginning of increasing complexity in life.
Mitochondria were crucial for seeding complexity in eukaryotic cells. Part 3 will explain why mitochondria allowed eukaryotes to ascend to higher complexity.
Mitochondria also drove eukaryotic evolution further up the ramp of increasing complexity. Part 4 will explain how mitochondria impelled eukaryotes to greater complexity.
While some argue the mergers and gene transfers that led to eukaryotes were mere “flukes”, the author disagrees and believes they played an essential role in eukaryotic evolution according to natural laws.
Cells/organisms that lose essential genes will not survive as they can no longer perform essential functions. But if a gene is non-essential, its loss or damage does not necessarily lead to death.
Primate ancestors lost the vitamin C gene millions of years ago but did not die out as their fruit-rich diet provided vitamin C. Remnants of the lost gene remain in our junk DNA.
Rickettsia bacteria have lost around 80% of their genome as many genes are non-essential when living inside host cells. Its genome contains relics of lost genes in junk DNA.
Free-living bacteria also lose unnecessary genes through random mutations to replicate faster, though they retain more genes than Rickettsia due to needing genes for survival outside hosts.
Experiments showed bacteria quickly lose extra plasmid DNA when unnecessary, demonstrating bacteria jettison extreme genes.
Bacteria can gain new genes via lateral gene transfer from other bacteria, compensating for gene loss. This allows redundancy in case conditions change.
Lateral transfer undermines classification of bacterial species and reconstruction of their evolutionary trees due to frequent gene swapping.
Bacteria face constantly changing environmental conditions that favor different genes over time. Only bacteria that retain an extensive repertoire of genes through lateral gene transfer can survive diverse exigencies.
Fast-replicating bacteria may be threatened in changing conditions unless they can acquire new genes from their environment through processes like conjugation. This allows them to combine rapid replication with genetic resilience.
Bacteria that lose and gain genes through lateral gene transfer will thrive over those that do not. Gene sharing through conjugation is an effective way for bacteria to pick up new genes without damaged genes.
There is a dynamic balance in bacteria between gene loss, which reduces genome size, and gene gain through lateral gene transfer according to need. Gene loss appears necessary for allowing rapid replication.
Unlike eukaryotic organelles, bacteria are limited in genome size, complexity, and physical size because they must respire across their external cell membrane. As bacteria grow, their surface area to volume ratio decreases, impacting respiratory and nutrient absorption efficiency.
Mycoplasma and Thermoplasma are two groups of prokaryotes that can survive without a cell wall.
Mycoplasma are microscopic bacteria that rely on fermentation rather than respiration for energy. They have minimal genomes and live as parasites or symbionts.
Thermoplasma are archaea that live in hot acidic springs. They do not need a cell wall because the acidic environment outside the cell acts as a “communal periplasm.” They maintain neutral pH inside the cell and generate a proton gradient for chemiosmosis.
However, Mycoplasma and Thermoplasma are relatively primitive and regressive compared to other bacteria due to their lack of energetic efficiency without a cell wall.
Mitochondria allowed eukaryotic cells to overcome these constraints by internalizing energy production. This freed the cell from needing an external cell wall and enabled much larger cell sizes in eukaryotes through increased mitochondrial surface area.
Larger sizes then opened up predatory and multicellular lifestyles, which are impossible for bacteria limited by energetic scales. This was a significant factor in the divergence and complexity of eukaryotes compared to prokaryotes.
Bacteria face selective pressures that prevent them from gaining complexity on par with eukaryotes. The critical pressures are speed of replication and energetic efficiency.
Larger bacterial size means slower replication due to larger genomes, and lower energetic efficiency due to relying on outer membrane respiration vs. internal membranes. This precludes phagocytosis.
Some bacteria have complex internal membranes but not full eukaryotic complexity, suggesting more than membrane structure is required.
Mitochondria could develop internal respiration by retaining genes specific to controlling respiration over large membrane areas. This allowed eukaryotes to divorce size from energetic constraints.
Bacteria lack this advantage - they freely transfer genes laterally and discard unnecessary ones, preventing the acquisition of the correct gene set for internal respiration. This has always prevented bacteria from evolving eukaryotic complexity naturally via symbiosis alone.

So, in summary, mitochondrial genes were vital in allowing eukaryotes to divorce size and complexity from energetic constraints, an advantage bacteria could not gain due to their different selective pressures and genetic dynamics.

Mitochondria originally had many genes but have lost the vast majority over time, probably thousands of genes. Some genes were lost, while others were transferred to the nucleus.
Gene transfer from mitochondria to the nucleus is shared in bacteria through lateral gene transfer. A similar process of genes being released from dying mitochondria and incorporated into the core likely accounted for many mitochondrial genes ending up in the nucleus.
Plant research found that chloroplast genes transfer to the nucleus at about one transfer per 16,000 seeds, demonstrating this transfer process happens regularly. Over 350 mitochondrial DNA sequences have also been found transferred to the human heart.
Gene transfer predominantly occurs from mitochondria to the nucleus but not vice versa, creating a “gene ratchet” favoring this transfer direction.
These transferred genes may have contributed to the evolution of the eukaryotic nucleus, as the shared bacterial membrane genes could have formed lipid vesicles around the chromosomes that became the nuclear membrane over time. This explains the bacterial-style membranes found throughout eukaryotic cells.

So, regular lateral gene transfer from mitochondria to the nucleus through dying organelles likely accounts for many mitochondrial genes ending up in the middle and may have played a role in the evolution of membrane systems and the nuclear membrane in eukaryotic cells.

Martin’s theory proposes that the eukaryotic cell could have evolved via a simple succession of steps from archaea and bacteria merger, resulting in a cell with key eukaryotic features like a nucleus, internal membranes, mitochondria, etc.
This hypothetical early eukaryotic cell may not have engulfed food whole via phagocytosis yet and may have resembled unicellular fungi that secrete digestive enzymes externally instead.
Gene transfer from mitochondria to the host cell nucleus could explain the origin of the eukaryotic cell without requiring new genetic innovations.
However, it raises the question of why any genes were retained in the mitochondria, given the disadvantages like copying many redundant mitochondrial genomes in each cell division.
The standard explanation is it takes evolutionary time for proteins to acquire targeting signals to be delivered back to mitochondria after nuclear import. Still, more is needed to explain why no species has lost all mitochondrial genes entirely.
Chance alone also does not fully explain the observation that all species have retained essentially the same core mitochondrial genes after independently losing over 95% of their original mitochondrial genome content in parallel.
Other proposed explanations for gene retention, like protein size limitations, have also been disproven, so the whole reason for retained mitochondrial genes still needs to be clarified from this summary.

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Power, Sex, Suicide Mitochondria and the meaning of life.pdf - Unknown