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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