Group Selection

Every new form of biological organization becomes a new unit of natural selection

Group selection has been a controversial topic in evolutionary studies. Indeed, the whole matter of where selection operates has been a confusing mess. Richard Dawkins battled his way to fame by arguing that genes were the target of selection, and that we as animal bodies were merely automata driven to unwittingly propagate them by various unconscious means. When considering the unit of selection, one could go even to the individual nucleotide, which is ultimately what is extinguished or propagated by the action of mutation and selection, plying its tiny oar towards the survival of its gene, its genome, its cell, its organism, its society, ... its blessed plot, this earth, this realm, this England!

Traditionally, the individual organism has been viewed as the main unit of selection. But can groups, when they form societies like bee hives or human tribes, be objects of selection as well? A paper reviewing the mathematics of evolution and selection makes the crucial distinction between the mechanism underlying heritability of traits, which might be a gene or nucleotide, and the unit of selection, which is the level of biological organization that exhibits traits upon which natural selection acts. The color of our eyes may be a cellular and organ-level trait, based on genes and nucleotides, but the unit of selection remains the individual, since that is where selection- via mate choice, disease, and whatever other ramifications eye color may have- acts directly to promote or inhibit reproduction. Likewise, social traits such as altruism, cooperation, detection and policing of cheaters, etc. may be in large degree be relevant and selected at the individual level, but at least some of their power and selectivity comes in the competition between groups, i.e. group selection.

It should be clear that selection happens at all sorts of levels, indeed at every level where a new form of biological organization emerges. The "unit of selection" is not singular, but manifold, and is defined, not absolutely, but by the level and properties of the trait being considered. We who inhabit multicellular bodies have pretty definitively ended competition / natural selection among the cells that compose us- those cells are not individual units of selection, since they do not persist after we are gone (even in the case of cancer where their replication has gone haywire). The closest might be competition among male sperm cells, which evidently do compete in their final voyage, though not to the extent of taking up arms against each other. Thus generally, our genes are only indirectly targets of selection, in that they generate traits that manifest on the cellular, individual, and indeed group level, with consequent selection at those levels and differential reproduction that change gene frequencies in the future.

This is called multi-level selection. The socio-biologists got into hot water back in the 1970's by asserting that group traits are at least in part biologically based, as are individual psychological traits, and thus that groups must act as units of selection. This did not sit well with the politically correct of the day, who wanted as a matter of principle to believe that humans (and especially subgroups such as ethnicities and races) are all created equal, and that any talk of heritability of traits such as intelligence, aggressiveness, altruism, etc. was, if not wrong, at least socially devisive and certainly damaging to a proper communist / constructivist view of the malleability of the human condition. While constructivist views of our social psychology, relations and conflicts certainly have significant truth, they can be taken too far, such as the arch-feminist idea that male-ness is purely a social construction, and that some counter-programming is all it would take to make a utopian, de-gendered world.

I'll scratch your back ...

But that is all in the past, and not only are social and group traits increasingly recognized as biological and to some degree heritable, but our evolutionary history is unthinkable without a lot of specific socially relevant traits being encoded, evolved, and put to the test in group-group competition, whether via direct competition or just relative success of independent groups without direct interaction. A set of papers made a review of this field and developed a general mathematical treatment of multi-level selection (MLS), postulating that any biological entity or level of organization can be a unit of selection- when traits can be defined pertaining to that level. This is especially relevant to emergent traits that can not be defined at lower levels of organization. 

Alcoholism, for instance, is hard to define at the cellular or single gene level, but can be easily defined at the organismal level. So it is selected at the level, where individuals suffer and die due to its effects and impair the lives of others along the way. While it necessarily has genetic components and heritability, and those genes can be thought of as being selected for or against, they often drag along many other genes, and have complex relations with other genes in the trait's expression, leaving the definition of the trait and its interaction with natural selection at the individual level. The unit of selection is a separate concept from the genetic and developmental processes that generate the trait. In alcoholism, the adult is the unit of selection, consituting a collection of characteristics that develop out of genes and other sources, whose frequencies may change based on that selection. 

"The genetical theory of MLS ... describes the action of group selection in terms of change in a genetical character. As discussed in the previous section, a genetical score may be assigned to any biological entity that contains genes – such as an entire population – and change in this genetical score can be computed, irrespective of how that population is subdivided into groups and individuals, or the biological level of organization at which the corresponding phenotype actually manifests. ... the theory of natural selection is ‘genetical’: this adjective pertains to the medium by which characters are inherited, rather than to the unit of selection itself."

 

It may be that all this is just a matter of convenience and book-keeping, as traits are defined (by us) on a macro basis. A gene's-eye view of the situation would focus on its own gains and losses in the rough and tumble of life. But in that case, we could not speak of alcoholism as a trait, but would have to speak of the gene's eye view of all the pressures it finds itself under, which would range widely over molecular, cellular territories and beyond, and violate our basic conceptions of a trait that is under natural selection. That is why a trait is defined at a particular level of organization where that characteristic becomes manifest, rather than at at gene level. There is no gene for alcoholism, though the trait is composed of / developed out of many heritable elements.

Imagine, in contrast, that alcoholism had no genetic component at all, but was purely random in genetic terms, not even affected by, say, genetic susceptibility to advertising blandishments. Such a trait would be subject to natural selection (i.e. death and other forms debility). But all that selection on the trait would have no effect on the next and future generations, due to its lack of heritability. It would have no genetic implications, by definition. So the unit of selection and trait being selected are separate issues from the genetic elements that might underpin it, particularly the degree or lack thereof of its genetic basis. 

While we are discussing this particular trait, it might be worth noting that in group terms, affinity to alcohol might be considered a positive trait, contributing to group bonding through the ages. Thus alcoholism might be a matter of stabilizing selection, trading off between its individual harms and its group benefits, particularly in the prehistoric setting where alcohol concentrations tended to be low, social controls strong, and alcoholism proper quite hard to develop.

This discussion, based on the paper series, is all based on the Price equation, which apparently underlies the field and is an extremely general statement / definition of natural selection. It contains basically two terms, which provide for a separation between the aspects of biological change derived from natural selection, and all the rest of the sources of change- drift, environmental change, etc. The selection portion it expresses as co-variation between traits in two populations (such as in successive generations) and the success of individuals (or other units of selection) carrying that trait. The whole equation rests on four key terms, none of which are explicitly genetic:

• The unit of selection- the biological organization that exhibits the trait, whether an individual, group, etc.
• The arena of selection- the population of units within which selection and evolution take place.
• The character under selection- the trait at issue, at whatever appropriate level of organization.
• The target of selection- the quantity (fitness) by which the character / trait is either good or bad, thus being selected.

As far as the unit of selection and the trait that pertains to that unit, any level will do, as long as it corresponds with a unit, or trait, that is definable to us and selectable in nature. 

"Between-group selection is directly analogous to standard, individual-level natural selection, but with the group taking on the role of the unit of selection, the group's phenotype acting as the character under selection and group fitness being the target of selection."    

"... by framing selection in its full generality from the outset, Price's equation reveals that kin and group selection are components of natural selection, and we obtain their dynamics by drawing them out of—rather than adding them into—the basic form of Price's equation. Moreover, by showing how the kin selection and group selection viewpoints both emerge from the mathematics of natural selection, Price's equation shows that these are not competing hypotheses for the evolution of social behaviour but simply different ways of conceptualizing the very same evolutionary process—and that a fierce, decades-long debate had been largely over nothing."

"For group selection to overcome selection within groups, less than one successfully reproducing migrant may be exchanged per two populations per population lifetime. ... Indeed, if groups are long lived, successful migrants must be very rare, and within-group inbreeding intense, for group selection to prevail over equally intense within-group selection."

Each level of selection can operate on many different traits, however, some of which may not directly conflict. So leaving aside the direct competition between individual and group interests, there is a rich field of action for group selection. This observation of the great sensistivity of group benefits to the rate of migration, especially for traits that conflict between individual and group benefits, gives us a clue about the origins of tribalism, which makes a practice of accentuating infinitesimal differences (or entirely imaginary ones) and using them to justify xenophobia, war, and genocide. It is a key legacy of evolution, particularly group evolution, and one that we struggle to overcome.

So group selection is perfectly consistent with evolutionary theory, (though some rather testy controversies remain). Does that mean that racism is OK? Do group differences justify tribalism and oppression? Well, our instinct for tribalism is certainly testament to a long evolutionary history of group selection, with its tireless focus on tiny, or even nonexistent, differences. The fact is that among humans, group differences are always swamped by within-group variation. We also do not generally discriminate so harshly against the differently abled and neuro-diverse *within tribes as we do against those we perceive outside them. So the practical and moral basis of discrimination and oppression is very poorly founded. True group selection is also virtually powerless against high migration rates, which we have throughout the modern world in any case. Thus the tribal instinct, which is now so flexibly deployed for nebulous groupings as nation states or sports teams, is totally out of its natural element, were we even inclined to mount some new eugenic project of any nature, whether individual or group.

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Remembrance of Climates Past

As the climate heats up, we are heading back in time, very rapidly.

Climate change is the challenge of our times and of our planet. However attractive it is to not care, to ignore it, to hide in traditional ways of thinking, to let inertia have its way, inexorable change getting worse by the year. The American way of life can not go on, and will not go on as before. This year has been a remarkable demonstration of the range of catastrophe, from melting Arctic villages to Pacific Northwest heat waves, California wildfires, record draught on the Colorado river, hurricanes running out of letters, and catastrophic floods in Europe. Migration crises around the world point to another implication- that as the global South becomes unlivable, increasing hordes of people will be knocking on the borders of the Northern countries, who have authored the mess.

To get some perspective on the change, we can look backwards into the geological record to see where we are going, and how fast. Earth has had a very diverse climatic history, from its beginning in a Venus-like cloud of high CO2 and no oxygen, to "snowball earth" freezes, to torrid warm periods extending to the poles. Over the last few billion years, earth's climate has had a fundamentally, if slowly, self-correcting mechanism based on CO2 production and consumption. CO2, needless to say at this point, is the main variable in our atmosphere's tendency to retain or give up solar heat. Volcanoes liberate CO2 from geologic and organic buried carbon. Organic carbon can also be liberated by fires and decomposition of organic carbon, including exposed coal, methane, and oil deposits. On the other hand, the biosphere fixes and buries carbon, and on an even more vast scale the weathering of exposed rocks drives the formation of carbonate minerals that lock up atmospheric CO2. When conditions are warm, weathering of rocks accelerates, as can organic fixation and burial, drawing down CO2. When conditions are cold, ice sheets cover the land and inhibit both organic fixation and rock weathering, allowing CO2 to build up in the atmosphere.

These cycles mean that over a scale of millions of years, earth does not get caught irretrievably (as Venus has) in an inhospitable climate. Instead, our recent ice ages ebbed and flowed, back and forth as the CO2 balance in the atmosphere responded fitfully to geologic conditions. The dramatic snowball periods, which occurred just before the Cambrian period, came to an end even though the earth-wide snow cover dramatically reduced solar absorbance. But it also reduced weathering and organic fixation of CO2, so eventually, CO2 built up to the very high levels needed to overcome the snowball effect and the climate snapped back to very warm conditions.

A key point in all of this is that climate change over earth's history has been driven geologically, and thus has been slow. Slowness has critical effects in allowing the biosphere to adapt. The typical driver is a new spate of volcanic eruptions, which release lots of CO2. This takes thousands of years to happen, so while this can be fast in geologic terms (a prime example is the Paleocene-Eocene thermal maximum, which took maybe 20,000 years to drive the climate from very warm to quite torrid, roughly 55 million years ago). However, the homeostatic mechanisms kicked in, and this torrid phase only lasted  a couple of hundred thousand years. Another example has been the slow uplift of the Tibetan plateau, which exposed a great deal of rock to weathering, thus drawing down atmospheric CO2. This is thought to have driven the cooler temperatures and glaciations of the last few million years.

A notorious exception is the K-T boundary extinction, where an asteroid hit the earth and changed the climate overnight. And life suffered correspondingly, with all the dinosaurs wiped out. (Well, all except for birds). Whatever was not pre-adapted somehow for this instant crisis failed to make it through. The stress this put on the biosphere is obvious, catastrophic, took many millions of years to recover from, and changed the trajectory of evolution dramatically.

An extremely rich graph of the last 70 million years of earth's climate, from a recent benchmark paper. Temperatures are shown on top right, while the isotopic findings that undergird them are shown on top left (temperature proxy based on oxygen isotopes) and bottom left (carbon concentration proxy based on carbon isotopes). The overall trend is correlation between the two, with CO2 the primary driver of higher temperature, and subject to swings for various geologic and biological reasons. Temperature is also affected secondarily by orbital mechanics and other factors. Even the Eocene high temperatures were driven by CO2, though the correlation is not so clear here.

What does all this mean for our current trajectory? The graph above helpfully supplies the current IPCC scenarios of temperature change, under stringent, medium, and business as usual scenarios. The temperature today (green) is already equivalent to conditions of about five million years ago. So in time machine terms, we have travelled, in the span of a century, five million years of climate history, to before the recent ice ages. We are already beyond the stringent scenario, obviously, so the only possible futures we have to look forward to are the medium and no-action scenarios, which, within the next fifty to one hundred years, will put us, in time machine terms, fourteen and forty million years into the past, respectively. And what of the century after that? CO2 stays in the atmosphere for many thousands of years, so not only do we have to reduce emissions now, we will have to remove those that have already happened. Climate stewardship will be humanity's job whether we like it or not.

The biosphere can not cope with this rate of change. While we often think in narcissistic terms of how humans will suffer, we are the lucky ones, being the most adaptable creatures ever devised by evolution. Our problems are nothing compared to the rest of the biosphere. The ability of animals to migrate or shift their ranges is highly strained by the availability of the rest of their essential networks, mostly based on plants at the base of the ecological network. And plants are not going to have the ability to migrate at these speeds and generate new ecosytems in more northerly areas. To us, the speed of climate change is slow, barely discernible on a lifetime scale. But in earth history terms, it is blindingly fast, just a blip over an asteroid impact, and far faster than normal ecosystem dynamics, let alone evolution, can cope with. Uncounted species are falling by the wayside, victims of another great extinction in earth history in this, the anthropocene geological epoch.

Time machines are exciting tropes of science fiction, allowing amazing journeys and byzantine plot twists. But usually, the outcome is not good, since changing the time line has unpredictable and sometimes catastrophic effects. Typically, a ruse is employed to extricate the heroes from the twisted plot, and everyone sighs with relief at the end when the normal time line is restored. Our climate path is not heading for such a happy ending. We are gambling, now consciously and willfully, with not only our own civilizational existence, but with the progressive and rapid degradation of the entire biosphere, on this warp-speed trip into the geological past.

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Squeezing Those Electrons For All They've Got

How respiratory complex I harnesses electron transfer from NADH to quinone to power the mitochondrial battery.

Energy- we can't live without it, we can't make it ourselves, and we use all sorts of complex technologies to harvest and store it. Solar power is reaching a crisis as we realize that it isn't going to work without storage. Life faced similar crises billions of years ago, and came up with core solutions that we know now as the chemical transformations of photosynthesis and metabolism. Plants make storage compounds from sunlight, which we in turn eat for energy, transforming them into a series of currencies from short- to long-lived, such as NADH, protons, ATP, glucose, and finally, fat.

Within us, the mitochondrion is the engine, not making energy, but burning it from the food we eat. The core citric acid cycle disassembles the reduced carbon compounds that serve as our food and longer-term storage compounds into oxidized CO2 and energy carriers NADH, FADH. While used widely in the cell for specialized needs, these compounds are not our core energy stores, and are generally sent to the electron transport chain for transmutation into a proton gradient that serves as the battery of the mitochondrion, which is in turn used to synthesize our general energy currency, ATP. ATP is used all over the cell for general needs, including the synthesis of glucose, glycogen, and fat as needed for longer term storage.

The discovery of the proton battery was one of the signal achievements of 20th century biochemistry, explaining how mitochondria, and bacteria generally, (from which they evolved), handle the energy harvested via the electron transport chain from food oxidation in an organized and efficient way, without any direct coupling to the ATP synthesis machinery. The electron transport chain is a series of protein complexes embedded in the innermost mitochondrial membrane that receive high-energy electrons from NADH / FADH made in the matrix through the citric acid cycle and use them to pump protons outwards. Then the ATP synthetase enzyme, which is another highly specialized and interesting story, uses the energy of those protons, flowing back in through its rotary structure, to synthesize ATP. The proton gradient is short-lived, a bit like our lithium batteries, continually needing to be recharged- a key form of storage, but just one part of a larger energy transformation system.

A recent pair of papers from the same lab, capitalizing on the new technologies of atomic structure determination, describe in new detail the structure of respiratory complex I, which is a huge complex of 45 proteins that receives NADH, conducts its two electrons to ubiquinone, and uses that energy to pump out four protons from the mitochondrial matrix. Not all questions are answered in these papers, but it is a fascinating look into the maw of this engine. Ubiquinone (often abbreviated as Q) is then later taken up by another respiratory complex that squeezes out a few more protons, while transferring the electrons to cytochrome C, which goes to yet another respiratory complex that squeezes out a final few protons.  Like in our macroscopic world, a lot of complicated machinery is needed to keep a power system humming. 

The complex hinges literally on the Q binding site, which is at the elbow between the intracellular portion that binds NADH, and the series of proteins that all sit in the membrane. When Q binds, the bend is larger, (called the closed form), and when it leaves, the bend is smaller (called the open form). The electron path through the paddle is reasonably well understood, going through several iron-sulfur and flavin mononucleotide complexes that have special overlapping quantum tuning to allow extremely efficient electron transport. The key to the whole system is how the transfer of electrons from NADH through the paddle domain down to Q, which protonates it to QH2 and makes it leave to travel through the membrane to its other destinations, is coupled with a long-range physical and electrostatic shift through the rest of the complex to run the proton pump cycle. 

Structure of complex I, emphasizing the electron path in the paddle (upper right) and the many possible proton conduction paths in the membrane-resident part of the complex (bottom). The Q binding site is shown in brown at the elbow. Each protein subunit is named and given a distinct color. A conductive "wire" through the middle of the membrane components is isolated from the solvent, but connected to each membrane side with dynamically gated pathways. Whether these gates have more of a physical character or an electrostatic character, or both, remains uncertain.

The membrane domain, made up of several similar proteins all side-by-side, seems to have a sort of wire running through the middle, made up of charged amino acid side chains and water molecules, capable of conducting protons parallel to the membrane. It also has specific proton conduction paths within each subunit that provide the possible entry and exit paths for protons getting pumped from the interior outwards. The authors propose that there is a sort of hokey-pokey going on, where one bent form (the open form, with Q ejected) of the machine exposes the matrix-side proton channels, while the other bent form (closed form, with Q present) closes those channels and opens a corresponding set of four channels on the other side that let those same protons out to the cell. The internal wire, they propose, may possibly redistribute the protons to buffer the input channels. Or it might even allow all four to exit on the last, fourth pump complex. In any case, this in essence is the core of biological pump designs, opening channels in one direction to capture protons from one side, (by diffusion), and then executing a switch that closes those and opens ports to the other side, again using diffusion to let them go, but in a new direction. It is the physical cycle that translates energy into chemical directionality, aka pumping.

Proposed mechanism, with the insertion or ejection of Ubiquinone Q dictating the  proton channel accessibility along the membrane proton pump subunits of complex I. Protons enter from the mitochondrial matrix in the blue structures (closed), and exit via the other side in the green structures (open).

Closeup of one of the membrane proton pump segments, showing the dynamic formation of one proton conduction channel in the "open" state (left) vs the closed state (right, circled). The somewhat dramatic turning of the center protein helix carrying residues M64 and F68 opens the way

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Rank	Country	Total Cases	New Cases	Total Deaths	New Deaths	Total Recovered	Active Cases	Serious, Critical	Tot Cases/1M	Deaths/1M
1	USA	27,798,163	+93,759	479,726	+3,219	17,631,858	9,686,579	21,446	83,682	1,444
83	China	89,720	+14	4,636	0	84,027	1,057	18	62	3

Viruses Have Always Been With Us

Some researchers argue that viruses form their own kingdom of life, and originated prior to the last common cellular ancestor.

Viruses are all about, even more of them than bacteria. The pandemic has focused our attention on one of them, but they are truly astronomical in diversity and numbers. Where did they come from? This has historically been thought a pointless question, since, even if one concedes that they are life forms of a sort, they mutate and evolve quite a bit faster than cells and organisms do, erasing most of their history. Additionally, they have been thought to exchange genes at a high rate with their hosts, also tending to erase whatever history they retain. But an article published back in 2015 fought back against all this pessimism, and made the case that virus histories can be reconstructed on a global scale and have some very interesting things to tell us.

Their first point is that gene exchange between viruses and hosts is less confusing than thought. Cells certainly have adopted viral genes at a high rate. Our own genomes are chock full of retroviral remnants, for instance. But functional genes are a different story. Relatively few seem to have gone either way (though see Koonin et al., arguing that many viral capsid and coat proteins were adopted from cellular genomes). The core viral replication proteins, such as the SARS-CoV2 RNA polymerase, for instance, is not related to cellular enzymes, and seems to be very ancient. The authors suggest that such key components originated even before the last common cellular ancestor- the point of divergence between archaea, bacteria, and eukaryotes.

To overcome the main technical hurdle of rapid evolution, the authors use protein fold analysis. Instead of studying DNA sequences, (which evolve quite rapidly), or protein sequences, (which evolve more slowly), this uses the shape of the protein, which tends to persist even after sequence similarity is completely lost. This is one way to get at very deep phylogenies, and they claim that it points to a substantial set of protein folds that are specific to viruses and wide-spread within viral families. They point out additionally that these proteins tend also to be confined to families of viruses, one more indication that virus evolution has not been promiscuous, but rather remarkably traceable through time. Viruses are classified into major families by their mode of replication. Thus RNA viruses and DNA viruses appear to have, for instance, distinct and ancient lineages.

One way to make sense of these observations and claims is that viruses were actually cells at very early times. It is common for parasites to progressively lose functions that are needed in the free-living state but become unnecessary when living off one's parents, er some other fully competent cell. The closer the symbiotic or parasitic association, the fewer functions the parasite needs. If the parasite is intracellular, then a huge amount of cellular overhead can be dispensed with. Mitochondria evolved this way, from free-living bacteria to organelles now with only about 33 genes. 

Viruses come in all sorts of sizes, from nearly cell size, encoding a thousand genes, down to specks of RNA only 250 nucleotides long. This diversity suggests the plausibility of their origination as cells, and subsequent down-scaling through a parasitic lifestyle.

But what were those cells, and whom did they parasitize? The distinct and peculiar gene complements and mechanisms of viruses, particularly the RNA viruses, suggests that they originated prior to the major split of existing cellular kingdoms. It stands to reason that cellular life has been saddled with parasites and viruses almost since the advent of cells, so some of these virus families may predate the advent of DNA, thus the prevalence of RNA viruses. The authors do an analysis of ages of the protein folds they find and their distribution, and suggest that those folds shared in all domains of life (viruses, archaea, bacteria, and eukaryotes) show that those from this set found in RNA viruses are significantly older than those found in DNA viruses. Such protein folds that are universal would be the most ancient, so finding differention among which viruses have them suggests that the major virus lineages come from different epochs of this most ancient era of cellular evolution. Interestingly, the pattern they do not find is one reflecting the cellular domains of life, which would be the case if viruses arise continuously or in relatively modern times from their cellular milieu.

Phylogenetic tree of protein folds from all domains of life, including viruses. Note the close clustering of RNA viruses near the root, and the early distribution of other viruses, compared to the later divergence of cellular domains. This kind of stretched phylogenetic tree is unfortunately symptomatic of an unsually high evolutionary rate, which is also a viral property. So it is not clear whether these authors have fully resolved this issue with their protein fold-based methods.

 

The upshot is that these authors promote the idea that viruses should constitute their own superkingdom of life, in parallel with the major cellular superkingdoms- archaea, bacteria, and eukaryotes. The rooting/ordering of the cellular tree remains quite controversial, but viruses are clearly something else again. They exchange a fair amount of genetic material with cells, but retain noticeable traces of early protein and RNA evolution. The idea that they arose from primitive or proto-cells also makes sense as a general proposition, for otherwise it is difficult to imagine their origin, such as from naked nucleic acids. This whole view remains quite controversial in the field, however, given the difficulties of the molecular analysis and the general prejudice against viruses as proper forms of life. But I think time will bear out this view and add a significant feature to early, as well as current, evolution.

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Evolution of the Larynx

Primates already had bigger and more diverse larynxes, before humans came on the scene.

While oxygen was originally a photosynthetic waste product and toxic to all life forms, we gradually got used to it. Some, especially the eukaryotes, made a virtue of oxygen's great electronegativity to adopt a new and more efficient metabolism with oxygen as the final electron acceptor. This allowed the evolution of large animals, which breathe oxygen. All this happened in the oceans. But it turns out that it is far easier to get oxygen from air than from water, leading air breathing to evolve independently dozens of times among fishes of all sorts of lineages. Lungs developed from many tissues, but rarely from the swim bladder, which had critical roles revolving around constant and controllable pressure, pretty much the opposite of what one needs in a lung. So in our lineage, the lung developed as an adjunct to the digestive system, where the fish could gulp air when gill breathing didn't cut it. 

Overview of the atmosphere of earth. Lungs were only possible when the level of oxygen in air rose sufficiently, and respiration of any kind only when oxygen had vanquished the originally reducing chemical environment.

This in turn naturally led to the need to keep food from going into the nascent lung, (air going into the stomach is less of a problem.. we still do that part), thus the primitive larynx, which just a bit of muscle constricting the passage to the lung. As this breathing system became more important, regulating access to the lung became more important as well, and the larynx developed more muscles to open as well as close the air passage, then a progessively more stable and complex surrounding structure made of cartilage to anchor all these muscles. 

But that was not the end of the story, since animals decided that they wanted to express themselves. Birds developed an entirely different organ, the syrinx, separate from the larynx and positioned at the first tracheal branch, which allows them to sing with great power and sometimes two different notes at once. But mammals developed vocal cords right in the center of the larynx, making use of the cartilaginous structure and the passing air to send one fluttering note out to the world. The tension with which these cords are held, the air velocity going past them, and the shapes used in the upper amplifying structures of the throat, mouth, and sinuses all affect the final sound, giving mammals their expressive range, such as it is.

So why are humans the only animals to fully develop these capacities, into music and speech? Virtually all other mammals have communicative abilities, often quite rich, like purrs, barks, squealing, mewling, rasping, and the like. But none of this approaches the facility we have evolved. A lot can be laid to the evolution of our brains and cognitive capacities, but some involves evolution of the larynx itself. A recent paper discussed its trajectory in the primate lineages.

Comparison of representative larynxes, showing a typical size difference.

The authors accumulate a large database of larynx anatomy and function- sizes, frequency patterns, evolutionary divergence times- and use this to show that on average, the primate lineage has larger larynxes than other mammals, and has experienced faster larynx evolution, to a larger spread of sizes and functions, than other mammals. The largest larynxes of all belong to black howler monkeys, who are notorious for their loudness. "The call can be heard up to 5 km away." They also claim that among primates, larynx size is less closely related to body size than it is among other mammals, suggesting again that there has been more direct selection for larynx characteristics in this lineage.

Primates (blue) show greater larynx size and variability than other carnivores.

This all indicates that in the runup to human evolution, there had already been a lot of evolutionary development of the larynx among primates, probably due to their social complexity and tendency to live in dense forested areas where communication is difficult by other means. Yet do primates have vocal languages, in any respect? No- their vocalizations are hardly more complex than those of birds. Their increased evolutionary flexibility at most laid the physical groundwork for the rapid development of human speech, which included a permanently descended larynx and more importantly, cognitive and motor changes to enable fine voluntary control in line with a more powerful conceptual apparatus.

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Why we Have Sex

Eukaryotes had to raise their game in the sex department.

Sex is very costly. On a biological level, not only does one have to put up with all the searching, displaying, courting, sharing, commitment, etc., but one gives up the ability to have children alone, by simple division, or parthanogenesis. Sex seems to be a fundamental development in the earliest stages of eukaryotic evolution, along with so many other innovative features that set us apart from bacteria. But sex is one of the oddest innovations, and demands its own explanation. 

Sex and other forms of mating confer one enormous genetic benefit, which is to allow good and bad mutations to be mixed up, separated, and redistributed, so that offspring with a high proportion of bad genes die off, and other offspring with a better collection can flourish. Organisms with no form of sex (that are clonal) can not get rid of bad mutations. Whatever mutations they have are passed to offspring, and since most mutations are bad, not good, this leads to a downward spiral of genetic decline, called Muller's ratchet.

It turns out that non-eukaryotes like bacteria do mate and recombine their genomes, and thus escape this fate. But their process is not nearly as organized or comprehesive as the whole-genome re-shuffling and mating that eukaryotes practice. What bacteria do is called lateral gene transfer, (LGT), because it typically involves short regions of their genomes, (a few genes), and can accept DNA from any sort of partner- they do not have to be the same species, though specific surface structures can promote mating within a species. Thus bacteria have frequently picked up genes from other species- the major limitation happens when the DNA arrives into the recipient cell, and needs to find a homologous region of the recipient's DNA. If it is too dissimilar, then no genetic recombination happens. (An exception is for small autonomous DNA elements like plasmids, which can be transferred wholesale without needing an homologous target in the recipient's genome. Antibiotic resistance genes are frequently passed around this way, for emergency selective adaptation!) This practice has a built-in virtue, in that the most populous bacteria locally will be contributing most of the donor DNA, so if a recipient bacterium wants to adapt to local conditions, it can do worse than try out some local DNA. On the other hand, there is also no going back. Once a foreign piece of DNA replaces the recipient's copy, there are no other copies to return to. If that DNA is bad, death ensues.

Two bacteria, connected by a sex pilus, which can conduct small amounts of DNA. This method is generally used to transfer autonomous genetic elements like plasmids, whereas environmental DNA is typically taken up during stress.

A recent paper modeled why this haphazard process was so thoroughly transformed by eukaryotes into the far more involving process we know and love. The authors argue that fundamentally, it was a question of genome size- that as eukaryotes transcended the energetic and size constraints of bacteria, their genomes grew as well- to a size that made the catch-as-catch-can mating strategy unable to keep up with the mutation rate. Greater size had another effect, of making populations smaller. Even with our modern billions, we are nothing in population terms compared to that of any respectable bacterium. This means that the value of positive mutations is higher, and the cost of negative mutations more severe, since each one counts for more of the whole population. Finding a way to reshuffle genes to preserve the best and discard the worst is imperative as populations get smaller.

Sex does several related things. The genes of each partner recombine randomly during meiosis, at a rate of a few recombination events per chromosome, thereby shuffling each haploid chromosome that was received from its parents. Second, each chromosome pair assorts randomly at meiosis, thereby again shuffling the parental genomes. Lastly, mating combines the genomes of two different partners (though inbreeding happens as well). All this results in a moderately thorough mixing of the genetic material at each generation. The resulting offspring are then a sampling of the two parental (and four grand-parental) genomes, succeeding if they get mostly the better genes, and not (frequently dying in utero) if they do not.

Additionally, eukaryotic sex gave rise to the diploid organism, with two copies of each gene, rather than the one copy that bacteria have. While some eukaryotes spend most of their lives in the haploid phase, and only briefly go through a diploid mated state, (yeasts are a good example of this lifestyle), most spend the bulk of their time as diploids, generating hapoid gametes for an extremely brief hapoid existence. The diploid provides the advantage of being able to ignore many deleterious genes, being a "carrier" for all those bad (recessive) mutations that are covered by a good allele. Mutations do not need to be eliminated immediately, taking a substantial load off the mating system to bring in replacements. (Indeed, some bacteria respond to stress by increasing promiscuity, taking in more DNA in case a genetic correction is needed, in addition to increasing their internal mutation rate.) A large fund of defective alleles can even become grist for evolutionary innovation. Still, for the species to persist, truly bad alleles need to be culled eventually- at a rate faster than that with which they appear.

The authors do a series of simulations with different genome sizes, mutation rates and sizes (DNA length) and rates of lateral gene transfer. Unfortunately, their figures are not very informative, but the logic is clear enough. The larger the genome, the higher the mutation load, assuming constant mutation rates. But LGT is a sporadic process, so correcting mutations takes not just a linearly higher rate of LGT, but some exponentially higher rate- a rate that is both insufficient to address all the mutations, but at the same time high enough to be both impractical and call into question what it means to be an individual of such a species. In their models, only when the length of LGT segments is a fair fraction of the whole genome size, (20%), and the rate quite high, like 10% of all individuals experiencing LGT once in their lifetimes, do organisms have a chance of escaping the ratchet of deleterious mutations.

" We considered a recombination length L = 0.2g [genome size], which is equivalent to 500 genes for a species with genome size of 2,500 genes – two orders of magnitude above the average estimated eDNA length in extant bacteria (Croucher et al., 2012). Recombination events of this magnitude are unknown among prokaryotes, possibly because of physical constraints on eDNA [environmental DNA] acquisition. ... In short, we show that LGT as actually practised by bacteria cannot prevent the degeneration of larger genomes. ... We suggest that systematic recombination across the entire bacterial genomes was a necessary development to preserve the integrity of the larger genomes that arose with the emergence of eukaryotes, giving a compelling explanation for the origin of meiotic sex."

But the authors argue that this scale of DNA length and frequency of uptake are quite unrealistic for actual bacteria. Bacterial LGT is constrained by the available DNA in the environment, and typically takes up only a few genes-worth of DNA. So as far as we know, this is not a process that would or could have scaled up to genomes of ten or one hundred fold larger size. Unfortunately, this is pretty much where the authors leave this work, without entering into an analysis of how meiotic recombination and re-assortment would function in these terms of forestalling the accumulation of deleterious mutations. They promise such insights in future work! But it is obvious that eukaryotic sex is in these terms an entirely different affair from bacterial LGT. Quite apart from featuring exchange and recombination across the entire length of the expanded genomes, it also ensures that only viable partners engage in genetic exchange, and simultaneously insulates them from any damage to their own genomes, instead placing the risk on their (presumably profuse) offspring. It buffers the effect of mutations by establishing a diploid state, and most importantly shuffles loci all over these recombined genomes so that deleterious mutations can be concentrated and eliminated in some offspring while others benefit from more fortunate combinations.

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The Gift

How to be thankful, without anyone to be thankful to.

Remember back when Barack Obama told business leaders that "you didn't build that"? He meant that they didn't build all the public goods that their businesses relied on- the roads, the legal system, the military defense, the regulatory bodies creating fair playing fields, the educational system. Businesses make it their business to be as myopic as possible, feeding off "business models" that foist as much cost onto others- workers, the government, the environment- as amorally possible. That is the only way to survive.

We all are a little like that, with tunnel vision focused on what we need, what we can get, and what we can do. Sometimes it is all one can do merely to survive in a world that seems so difficult, competitive, even hostile. But at the same time, who and what are "we"? Is our next need the full measure of our place in reality? Our focus on doing and on agency is a highly misleading aspect of consciousness. It presupposes a gazillion things that we have no agency over, couldn't even if we tried, and couldn't understand in any case. We didn't make our bodies, for one thing. This biology that we think we are so familiar with is, to biologists, incredibly inscrutible. The trillions of cells, billions of neurons, gajillions of molecules, all work away in obscurity to make us go. But are we thankful? Rarely. We didn't make them. We don't even understand them, and a century or two ago, we really, really didn't understand them. They are utterly alien. Yet they are also us.

The story goes similarly with everything else about us- the flow of time and fate, the universe we live in. All these are, at a fundamental level, still hardly understood. Where did all the energy of the big bang come from? What did it expand into? Why did it cool into the particles of physics? Are there other universes? No idea. And even if we had an idea, we weren't there and didn't make it happen. We are recipients, not actors, in this most vast drama. We should not be distracted by the competitive social systems we live in, and the pressing difficulties of life, to forget that we, as the conscious "I" of an individual human, are mysterious feathers floating on rivers of unplumbed unconscious depths, in a rich forest of abundance, on a planet mild and pleasant, in a universe that rendered these provisions in fantastic plentitude, to us and possibly to countless other worlds as well.

The lilies of the field, well, they toil quite hard, actually, in their own way. But that may not be apparent to the homilist, and took some science to figure out.

There needn't have been an intention behind all this- to conjure a cosmos, and evolve life. Indeed, it is rather unlikely given the little we do know. At any rate, we have speculated long and hard enough to know that more speculation isn't going to get us very far, or obtain any brownie points. We are, regardless, the benificiaries of these gifts. This is a, perhaps the, fundamental religious feeling- thankfulness for the infinite powers and entities that we embody, experience, and rely on, yet have precious little understanding of- the mysterium tremendum.

Does this all imply god? No. God is a rather pathetically inferred solution to, or better yet, an anthropomorphization of, this mystery. As social beings, and products of families, we in a primitive state might naturally ascribe the vast mysteries that undergird our existence and far outstrip our conceptions to a personified father figure (or mother, if one's society happens to be matriarchial). No error could be more obvious. Science has served to push the boundaries of mystery a little farther out, from a choking fog where virtually everything is obscure, to a view that goes billions of light-years across the universe. What all this has shown is, that as far as we can see, mechanism is the rule. Our bodies are mechanisms. The universe is a mechanism. Diseases are not the vengeance of jealous gods, nor is the weather. The inference of god has not held up well over time- not well at all. Yet that does not mean that we shouldn't be thankful for the gifts we receive, which are so rich on our life-giving planet. Nor that we shouldn't strive to pass them on rather than destroying them in the current moment of greed, by our thoughtless overpopulation and immiseration of this world.

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Eating the Wild Things

Despite humanity's long tradition of eating wildlife, it is high time to rethink it as a practice. 

The coronavirus outbreak certainly gives one pause, and time to think about what we are doing to the biosphere and to ourselves. It also makes one wonder about the wisdom of killing and eating wildlife. I have been reading a book about a different disaster, the struggles of the crew of the ship Essex, back in 1820. This Nantucket-based factory ship was hunting whales in the middle of the Pacific when, in an ironic, yet all too-rare turn of events, a huge male sperm whale rammed and sank the mother ship as the smaller whaleboats were out killing its relatives. Months of drama, extremity, and cannibalism ensue, (for the humans), after which a fraction of the crew survive to tell the tale. It seems to us now bizarre, and beyond wasteful, that street lights in Nantucket were lit with whale oil, and that people would sail all over the world's oceans just to kill whales for the oil in their heads and blubber. Humans have an instinct for survival, and for the most concentrated source of various goods, and, whether under the colors of capitalism or simple greed, think little of externalizing costs, no matter how brutal and far-reaching, whether eating each other, "fishing out" some rich source of food, causing extinctions, or setting Charles island of the Galapagos ablaze in an inferno (another episode that occurs in this ill-starred history). One must be "hard" in this business of living, after all.

Well, we can do better. Now, two centuries on, we are still abusing the biosphere. Some ways are new, (climate change, plastics, insecticides), but others are old, such as over-fishing. Factory ships are still plying the great oceans of the world, vacuuming up wild animals so that we can eat them. And not just do they derange whole ecosystems and litter the oceans with their waste, but they also kill a lot of innocent bystanders, euphemistically called "bycatch"- sea turtles, albatrosses, dolphins, whales, etc. Albatross populations are in steady decline, from very low levels and heading towards extinction, for one main reason, which is the fishing industry.

This simply has to stop. It is a tragedy of the commons, on a collossal scale, all for the atavistic desire to eat wild animals. Human overpopulation, coupled with technology, means that no wild animals stand a chance in an unregulated environment- not in Africa, not in Brazil, and not in the international oceans. We are killing them by a thousand cuts, but do we also have to eat them, as the final indignity and form of waste?

If we want to save the biosphere from utter impoverishment, humanity needs a change of heart- an ethic for keeping the wild biosphere wild, rather than running it like so much farmland, or so much "resource" to be pillaged, whether "sustainably" or not. Obviously, eating meat at all is a fraught issue- ethically, and environmentally. But surely we can agree that wild animals, and wild ecosystems, deserve a break? Conversely, where we have so screwed up ecosystems by eliminating natural predators or introducing invasive species, we may have to kill (and yes, perhaps eat) wild animals in systematic fashion, to bring back a functional balance. Go to town on feral hogs, boa constrictors, Asian carp, etc. (But try to do so without poisoning yourselves and the evironment with lead.) The point is that we are stewards of this Earth now, like it or not, and ensuing generations over the next hundreds and thousands of years deserve an Earth with a functioning biosphere, with some semblance of its original richness.

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Origin of Life- RNA Only, or Proteins Too?

Proteins as Participants in the Origin of Life

After going through some momentous epochs in the history of life in the last two weeks (the origin of eukaryotes, and the nature of the original metabolism), we are only part of the way to the origin of life itself. The last common ancestor of all life, (LUCA), rooted at the divergence between bacteria and archaea, was a fully fledged cell, with many genes, a replication system and translation system, membranes, and a robust metabolism based on a putative locale at hydrothermal vents. This is a stage long after the origination of life, about which our concepts remain far hazier, at the chemical interface of early Earth.

A recent paper (and prior) takes a few more speculative shots at this question, (invoking what it calls the initial Darwinian ancestor, or IDA), making the observation that proteins are probably as fundamental as RNA to this origination event. One popular model has been the "RNA world", based on the discovery that RNA has some catalytic capability, making it in principle capable of being the Ur-genetic code as well as the Ur-enzyme that replicated that same code into active, catalytic molecules, i.e., itself. But not only has such a polymathic molecule been impossible to construct in the lab, the theory is also problematic.

Firstly, RNA has some catalytic ability, but not nearly as much as it needs to make a running start at evolution. Second, there is a great symmetry in the mechanisms of life- proteins make RNA and other nucleic acids, as polymerases, while RNA makes proteins, via the great machine of the ribosome. This seems like a deep truth and reflection of our origins. It is probable that proteins would, in theory, be quite capable of forming the ribosomal core machinery- and much more efficiently- with the exception of the tRNA codon interpretation system that interacts closely with the mRNA template. But they haven't and don't. We have ended up with a byzantine and inefficient ribosome, which centers on an RNA-based catalytic mechanism and soaks up a huge proportion of cellular resources, due to what looks like a historical event of great significance. In a similar vein, the authors also find it hard to understand how, if RNA had managed to replicate itself in a fully RNA-based world, how it managed to hand off those functions to proteins later on, when the translation function never was. (It is worth noting that the spliceosome is another RNA-based machine that is large and inefficient.)

The basic pathways of information in biology. We are currently under siege by an organism that uses an RNA-dependent RNA polymerase to make, not nonsense RNA, but copies of itself and other messages by which it blows apart our lung cells. Reverse transcriptases, copying RNA into DNA, characterize retro-viruses like HIV, which burrow into our genomes.

This thinking leads to a modified version of the RNA world concept, suggesting that RNA is not sufficient by itself, though it was clearly central. It also leads to questions about nascent systems for making proteins. The ribosome has an active site that lines up three tRNAs in a production line over the mRNA template, so that the amino acids attached on their other ends can be lined up likewise and progressively linked into a protein chain. One can imagine this process originating in much simpler RNA-amino acid complexes that were lined up haphazardly on short RNA templates to make tiny proteins, given conducive chemical conditions. (Though conditions may not have been very conducive.) Even a slight bias in the coding for these peptides would have led to a selective cycle that increased fidelity, assuming that the products provided some function, however marginal. This is far from making a polymerase for RNA, however, so the origin and propagation mechanisms for the RNA remain open.

"The second important demonstration will be that a short peptide is able to act as an RNA-dependent RNA polymerase."
- The authors, making in passing what is a rather demanding statement.

The point is that at the inception of life, to have any hope of achieving the overall cycle of selection going between an information store and some function which it embodies or encodes, proteins, however short, need to participate as functional components, and products of encoding, founding a cycle that remains at the heart of life today. The fact that RNA has any catalytic ability at all is a testament to the general promiscuity of chemistry- that tinkering tends to be rewarded. Proteins, even in exceedingly short forms, provide a far greater, and code-able, chemical functionality that is not available from either RNA (poor chemical functionality) or ambient minerals (which have important, but also limited, chemical functionality, and are difficult to envision as useful in polymeric, coded form). Very little of the relevant early chemistries needed to be coded originally, however. The early setting of life seems to have been rich with chemical energy and diverse minerals and carbon compounds, so the trick was to unite a simplest possible code with simple coded functions. Unfortunately, despite decades of work and thought, the nature of this system, or even a firm idea of what would be minimally required, remains a work in progress.

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Turning Biochemistry on its Head in Search of the Origin of Life

Early earth was anoxic. That means that metabolic reactions ran backwards, compared to what we regard as normal.

Following up on last week's post on the origins of eukaryotes, I ran across a brilliant body of work by William Martin and colleagues, which explores both that and the related topic of the origin of life, all of which took place on an early earth very different from our own. Perhaps the most fundamental theme in any biochemistry course, especially when it comes to metabolism, is controlled oxidation. We in our bodies recapitulate the action of fire, by transforming (reduced) hydrogen-rich carbon compounds (carbo-hydrates, fats, etc.) to the most oxidized form of carbon, CO2, which we regard as a waste product and make- from our food, and now by proxy out of our ramified economic metabolism- in prodigious amounts. Our rich metabolic inheritance essentially slows down and harnesses this energy-liberating process that, uncontrolled, runs wild.

But early earth was anoxic. There was no free oxygen, and this metabolism simply could not exist. The great oxygenation event of roughly 2 to 3 billion years ago came about due to evolution of photosynthesis, which regards CO2 as its input, and O2 as its waste product. Yet plants metabolize the other way around as well, (often at night), respiring the reduced carbon that they painstakingly accumulate from CO2 fixation back to CO2 for their growth and maintenance. Plants are firmly part of this oxidized world, even as they, in net terms, fix carbon from CO2 and release oxygen.

An energy rich, but reducing, environment, full of sulfides and other hydrogen-rich compounds.

In a truly anoxic world, the natural biochemical destination is reduced compounds, not oxidized ones. The deep-ocean hydrothermal vent has been taken as a paradigmatic setting, at least as common on the very early earth as today. Here, reduction is the order of the day, with electrons rampant, and serpentinzation a driving mineral process, which liberates reducing power, and generates methane and hydrogen sulfide. This is one home of anaerobic life- an under-appreciated demimond of micro-organisms that today still permeate deep sediments, rocks, hydrothermal vents, and other geologic settings we regard as "inhospitable". An example is the methanogens- archaea that fix CO2 using the local reducing power of hydrogen, and emit methane. Methane! A compound we in our oxygen atmosphere regard as energy-rich and burn in vast amounts, these archaea regard as a waste product. The reason is that they live where reduction, not oxidation, is the order of the day, and they slow down and harness that ambient (chemical gradient) power just as we do in reverse. This division of aerobic vs anaerobic, which implies metabolisms that run in opposite directions, is fundamental, accounting for the hidden nature of these communities, and why oxygen is so toxic to their members.

By now it is quite well known that not only was the early earth, and thus early life, anoxic; but the broadest phylogenies of life that look for our most distant ancestors using molecular sequences also place anaerobes like methanogenic archaea and acetogenic bacteria at the earliest points. Whether archaea or bacteria came first is not clear- they branch very deeply, and perhaps earlier than any phylogenetic method using the molecular clues can ever tell. Thus the archaeal progenitor of the eukaryotic host appears to have been anaerobic, and may have entered into a dependence with a hydrogen-generating, methane-using bacterium which had already evolved an extensive metabolism compatible with oxygen, but not yet dependent on it. It was only later that the oxygen-using capacity of this partner come to such prominence, after oxygen came to dominate the biosphere so completely, and after the partner had replaced most of the host's metabolism with its own enzymes for heterotrophic use (i.e. fermentation) of complex carbon compounds.

This overturns the image that was originally fostered by Darwin, in a rare lapse of prophetic skill, who imagined life originating in a quiet sunlit pool, the primordial soup that has been sought like a holy grail. The Miller-Urey experiments were premised on having complex compounds available in such a broth, so that heterotrophic nascent cells just had to reach out an choose what they wanted. But these ideas above end up proposing that life did not begin in a soup, rather, it began in a chemical vortex, possibly a very hot one, where nascent cells built an autotrophic metabolism based on reducing/fixing carbon from CO2, (the dominant form of carbon on early earth), using the abundant ambient reducing power, and local minerals as catalysts. Thus the energetics and metabolism were established first, on a highly sustainable basis, after which complexities like cell formation, the transition from mineral to hybrid mineral/organic catalysts, and the elaboration of RNA for catalysis and replication, could happen.

Much of this remains speculative, but one tell-tale is the minerals that underpin much of metabolism. Iron-sulfur complexes still lie at the heart of many electron transfer catalysts, as do several other key metals. RNA is also prone to oxidation, so would have been more robust in an anoxic world. More generally, this theory may widen our opinions about life on other planets. Oxygen may be a sign of some forms of life, and essential for us, but is hardly necessary for the presence of life at all. Exotic places with complex chemistries, such as the gas giant planets, may have fostered life in forms we are unfamiliar with.

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Mother of us All- the Eukaryotic Ancestor

A new archaeon looks very much like an early transitional form between archaea and eukaryotes.

Even more than the invention of photosynthesis or the transition to multicellularity, the transition from bacteria to eukaryotes was perhaps the most dramatic and momentous evolutionary event after the origination of life. Bacteria are everywhere, and still dominate the biosphere in many respects with an unparalleled range of biochemistries. But they have severely limited prospects, being so streamlined in their genetic and sexual practices that they seem unable to escape their single-celled, remorselessly competitive fate.

Eukaryotes are known to have originated in the fusion of at least two different bacteria-like microorganisms, one perhaps an amoeba-like hunter, the other the bacterium that became our mitochondrion. Plus another that in plants became the chloroplast. There are several theories about the details, of which several propose metabolic symbiosis- that the original exchange between the mitochondrial progenitor and its host was actually not amoeboid engulfment, but quite gradual and voluntary, uniting a methanogenic partner that used small organic compounds and hydrogen as its inputs- making methane- with a methanotrophic host that produced various organic compounds from methane plus CO2 without complaint.

But once joined, eukaryotes did so much more, generating countless innovations in cell organization, sex, genetic control, organelle subspecialization, membrane management, cytoskeletal structure, among others, that it is hard to believe this event ever happened, and difficult to reconstruct its steps. In this regard, it is similar to the origination of life, where several obstacles (enclosure of a cell with selective transport, replicative mechanism, and metabolic power, perhaps among others as yet unappreciated) all had to be surmounted in some fashion before something that we would call life existed- a process that remains a topic of wide-ranging speculation.

But the starting point for eukaryotes seems to have been an archaeon- a member of the third major kingdom of life discovered only in the 1970's, which are unicellular like bacteria, but have many distinct molecular and genetic mechanisms that are more closely related to eukaryotes than to bacteria. These seem to be our nuclear ancestors, with a lot of bacterial genetic material added later on, either from the early mitochondrial symbiont, or from other transfers, which enriched their biochemical range. The big questions are- what caused the unification of these two life forms, and why did it result in such an extensive profusion of other innovative traits? A recent paper (review) is devoted to the first question to some degree, discovering a new archaeal species that is the closest yet to such a transitional form.

"We confirmed the presence of 80 eukaryotic signature proteins, which are also observed in related Asgard archaea."

To do this, they cultivated deep marine sediments from around Japan in an oxygen-free bioreactor, feeding methane (plus a bunch of antibiotics, to kill off any bacteria) in order to cultivate organisms that are notoriously hard to cultivate. They were looking for anaerobic archaea that die in oxygen, and live off of methane, which they get typically from partner bacteria. The hydrogen that the former (methanotrophs) produce from methane is toxic in large amounts, so having a partner to use it and give methane in return is a partnership made in heaven. Those partners (at first, methanogens) eat hydrogen and CO2, or other small organic molecules and produce methane. The new methanotroph is not just picky about conditions it will grow in, but extremely slow-growing, doubling in the best of conditions in about 20 days. These are not E. coli! Indeed, the whole project took a decade.

The idea to culture such obscure and obdurate organisms comes from two sources. First were existing hypotheses about how eukaryotes got started, in the form of metabolic collaborations described above, between disparate micro-organisms, centering on the use and exchange of methane and hydrogen, in addition to electrons and other compounds. Second were surveys of marine sediments and many other habitats for raw DNA, which has been sequenced in vast amounts. Such DNA is obviously a messy mixture, but given enough patience and computer power, one can re-assemble many interesting distinct genomes out of it, and some transition-like genomes have been glimpsed in this way. But what could be the corresponding organism? That was the question.

The author's phylogenetic tree across all kingdoms, using ribosomal proteins, highlighting the new organism's (red) position as sister group between archaea and eukaryotes. Note how relatively deep the divergence (X-axis) is between bacteria at the bottoms, and all other life forms.

One key analysis was to put this new organism into a phylogenetic tree, using the incredibly well-conserved sequences of the ribosomal proteins. The diagram above shows that the new organism, dubbed MK-D1, sits right at the threshold of the eukaryotic group, just as one would expect for an ancestor. It constitutes, to date and in molecular terms, the closest organism to eukaryotes that is not one itself. The diagram also shows, yet again, the vast molecular gulf between bacteria (at the very bottom) and archaea, which occupy most of the middle. While eukaryotes (top) are clearly a sister group of archaea, it is the divide between archaea and bacteria that is the most profound within the whole biosphere.

These new organisms are unexpectedly small- tiny, indeed. They are not the huge phagocytic amoeba that have often been imagined engulfing hapless bacterial partners about to be taken hostage. No, the methanogenic partners that are co-cultured by these researchers are far larger, by roughly ten-fold. But the new methanotroph has some interesting behaviors, such as putting out extensive cell projections and curious vesicles. It also has, as expected, a variety of genes that characterize eukaryotes, such as actin, profilin, Ras, G-beta like protein, TPR motifs, Zinc finger and HTH proteins, core transcription proteins like TFIIB, SMC, Ankyrin motifs, histones, SNARE-like proteins, signal recognition factor.

Micrographs of the new organism, MK-D1. Left is a high-magnification electron micrograph showing membrane vesicles budding off the main cell. Scale, 200 nm. Right is a scanning electron micrograph of two or three cells with dramatic projections emerging, plus some previously budded vesicles lying about. Scale, 1 micron.

Of course, this organism exists now, a couple billion years after its imagined ancestor occured in a lineage that we speculate was related to one that led to eukaryotes. So it is a stretch to make this diagnosis of a transitional form. Except that relict forms seem to litter the biosphere, such as the stromatolites that still crop up in Australia, and the vast hordes of bacteria and archaea that remain the metabolic engines of the biosphere, in perpetual competition, yet also largely frozen in their lifestyles and roles.

When free oxygen was introduced into the biosphere by nascent photosynthesis, starting roughly two and a half billion years ago, the putative methane-exchanging organisms all needed extra partners to detoxify it, for instance bacteria which oxidize (using O2) organic compounds to CO2. This, finally, was the motivating force for the partnership with the true mitochondrion, which performs the same service today, providing enormous amounts of energy along the way. The transition from the loose partnership cultured by the current researchers to the one that truly gave rise to eukaryotes is a bit murky under their class of hypotheses, but there are other hypotheses that make a more direct job of it.

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