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Another step towards answering the question of life's origins - science

Tharmas

Tharmas

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An interesting article in the Washington Post adds momentum to the RNA world theory. Self-replicating RNA has been created in a lab. The copies made are quite similar to the original, which has apparently been a stumbling block to earlier efforts. We are inching forward to the creation of life in a test tube.
 
One could just as easily say that since RNA could be created without divine intervention then score one for the evolutionists.

The point is that your statement is essentially empty rhetoric and has little if any probative value.

*Though I admit I did not read the paper, so I can’t be sure if divine intervention wasn’t one of the steps of their process.
 
Shadowy Man said:
The point is that your statement is essentially empty rhetoric and has little if any probative value.
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It has exactly the same value as the claim that as gold can be created by the neutron bombardment of mercury, all gold was created by the neutron bombardment of mercury, and that gold is therefore an artificial element and doesn't occur naturally.

That is, his statement is essentially nonsense.
 
All that aside, the origin of the first organism remains an unsolved problem.

One can go bottom-up, with prebiotic chemistry, or top-down, with evolutionary biology, and the two efforts still have not met.

In prebiotic chemistry, we have made some kinds of building blocks, like the smaller amino acids and some nucleobases, but it's hard to get an organism out of them, and some building blocks continue to be difficult to make prebiotically, like ribose.

In evolution, we have made remarkable progress. Before we could sequence anything, we were able to find reasonably-good family trees of many macroscopic organisms, though that effort was not nearly as successful for microscopic ones, especially one-celled ones.

 Frederick Sanger - in 1951 and 1952, he sequenced each amino-acid chain of bovine insulin, the first protein sequence ever found. It was painstaking work, doing  Edman degradation by hand, a technique invented by  Pehr Victor Edman But in 1967, he succeeded in automating this process - A revolution in protein sequencing: Case Study | NHMRC - in the early 1990's, mass spectrometry became used for protein sequencing - Methods and Techniques for Protein Sequencing - Creative Proteomics

By 1976, over 80,000 amino acids had been sequenced in various laboratories, and by 2017, 70 million.

A History of Sequencing of nucleic acids, DNA and RNA

In 1964,  Robert W. Holley sequenced alanine transfer RNA, in 1972  Walter Fiers sequenced a gene, and in 1976, the entire genome (3,569 base pairs) from bacteriophage MS2, a kind of virus that infects bacteria.

In 1977, Frederick Sanger struck again, developing the "dideoxy" method of terminating DNA chains:  Sanger sequencing - in 1981, human mitochondrial DNA (16,569 base pairs), and in 1982, bacteriophage lambda (48,502 base pairs).

Since then, a lot has been done to automate and speed up gene sequencing, with new techniques like "pyrosequencing", making it cost much less per nucleobase or base pair.

From that history of sequencing,
The Human Genome Project was the international research effort to determine the DNA sequence of the entire human genome. It took 13 years and was published in 2003, with an estimated cost of over $300 million. Today, a whole human genome can be sequenced in one day for under $1000.

The 100,000 Genomes Project was first announced by UK Prime Minister David Cameron in December 2012, resulting in the creation of Genomics England. In December 2018, the full 100,000 genomes milestone was reached, taking over half the time that sequencing just one genome took in 2003.
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Another history: The sequence of sequencers: The history of sequencing DNA - PMC

 List of sequenced eukaryotic genomes
  • 1995: bacterium Haemophilus influenzae - 1,830,138 bp
  • 1996: Brewer's yeast Saccharomyces cerevisiae -12,156,677 bp
  • 1998: Nematode Caenorhabditis elegans - 101.169 million bp
  • 2000: Fruit fly Drosophila melanogaster - 139.5 million bp
  • 2001 (draft), 2006 (complete) Human Homo sapiens - 3.2 billion bp
So we now have a huge pile of sequence data. What have we been able to do with it?
 
I remember long ago reading a book about biochemistry and being very intrigued with a remarkable result from comparing sequences of a protein called cytochrome c. Back then, it was mostly proteins sequenced, but comparing those sequences gave good agreement with the phylogenies worked out from macroscopic features. One could calibrate this protein's family tree using known or likely divergence dates, like between insects and vertebrates, nearly 600 million years ago.

But when one compared animals, plants, and fungi, one found a sequence distance almost twice as long, indicating an age of 1.2 billion years, thus looking back into a time when fossils were very rare.

Since then, it's been possible to look back even farther in time by comparing protein and gene sequences.

In the 1970's,  Carl Woese and his colleagues were working on the overall family tree of all our planet's cellular organisms. They decided on small subunit ribosomal RNA (SSU rRNA) to sequence, since every cellular organism has it. It is about 1,500 nucleotides long in prokaryotes and 2,000 nt long in eukaryotes, so it was a challenge to sequence back then. So they used an enzyme that cut up the molecules and then sequenced the fragments. But that nevertheless gave good results.

They were sequencing SSU rRNA's, finding a split between prokaryotes and eukaryotes, what one would expect, when one day they sequenced a very odd organism, a methanogen. This organism gets its energy from combining H2 and CO2 to make H2O and CH4, it makes all its biological molecules, like a plant does, (it is autotrophic), and it prefers to live without oxygen (it is anaerobic).

It was obviously a prokaryote, but it was very distant from the other prokaryotes, as much as the eukaryotes were.

They decided that methanogens and ordinary bacteria were separate "domains" of life, comparable to eukaryotes.

It took some time before that was generally accepted, since it wasn't very obvious that methanogens are all that different from other prokaryotes. But other genes agreed with that assessment, as did various phenotypic features: cell-membrane lipids (fatty acids vs. terpenes), cell-wall composition (peptidoglycan vs. various other stuff), ...
 
Life's origin is a fascinating question of SCIENCE, but except for lpetrich most of the reaction here has been about the connection to GOD!

Recently scientists -- of whom Nick Lane is most visible, with his books like The Vital Question and Life Ascending -- have probably solved the mystery of life's origin. Life arose in the micropores of alkaline hydrothermal vents on the ocean floor. This venue serves the needs of the earliest proto-life so well that Lane speculates that any life on other planets is likely to have begun very similarly. All of Earth's life uses chemiosmosis as part of its energy metabolism, mimicking the energy available for free in those micropores.

Earliest life's needs include (1) raw materials, (2) catalysts, (3) containment, (4) waste disposal, (5) self-reproducing complex chemicals, (6) evolution, and (7) energy. It seems to be the energy which is hardest to come by.

A huge amount of evolution was necessary to get to LUCA (the Last Universal Common Ancestor of all known life), since all life uses the genetic code and exquisite machinery like ribosomes and ATP synthase. This evolution required huge amounts of growth and reproduction; these in turn required huge amounts of energy. But where did the energy for earliest life come from? It couldn't come from life's own complicated chemical processes like photosynthesis since these were a RESULT of the evolution for which energy was PREREQUISITE.

Thus it was a great scientific triumph to deduce that life arose in the "white smokers" on the ocean floor. (But not in the much hotter "black smokers.") It was  Michael Russell (scientist) who first speculated that these alkaline "white smokers" were the venue for life's origin and impressively he did this BEFORE the first "white smoker" was even discovered on the sea-bed!

ETA: His speculations date to the early 1990's. The "Lost City" white smokers in the mid-Atlantic were discovered in the year 2000.
 
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The three domains are Eubacteria / Bacteria, Archaebacteria / Archaea, and Eukarya.

But how is Eukarya related to the others? Chloroplasts are descended from cyanobacteria (blue-green algae), and mitochondria from alpha-proteobacteria, but the rest of the cell? The informational features are Archaea-like, while the metabolic features and the cell-membrane lipids are Bacteria-like. The chloroplast was gained by a later eukaryote, and was the mitochondrion also? But many mitochondrion-less eukaryotes have evidence of the former presence of those organelles, and it's evident that the ancestral eukaryote had mitochondria. So that organism was some mishmash of several organisms, a Frankenstein organism.

Loki and behold: one microbial culture that brings us one leap closer to understanding the origins of eukaryotic cells | The Molecular Ecologist

The easy sequencing of a large amount of genetic material has made possible a remarkable new field: environmental genomics. One sequences the genetic material in an environment sample and tries to find the closest relatives of the sequences that one finds. This led to the discovery of some Archaea microbes that are especially close to eukaryotes: the Lokiarchaeota. Some researchers very patiently grew some of these organisms in their lab over 12 years, taking that long because these organisms are very slow-growing, because of their very limited nutrition in seafloor mud. Once these organisms were grown enough, the researchers sequenced those organisms' genomes. Those organisms turned out to be what they surmised from the environmental-sample sequencing: the closest prokaryotes to eukaryotes yet found, at least eukaryotes' informational systems.
 
As a result of all the protein and gene sequencing that we have done, we now have an outline of the phylogeny of all the world's cellular organisms, an outline that is largely very well-tested, though many parts continue to be poorly resolved.

Bilateria: bilaterally-symmetric animals:
  • Protostomia
    • Ecdysozoa: arthropods, onychophorans (velvet worms), tardigrades, nematodes, ...
    • Lophotrochozoa: molluscs, annelids, flatworms, rotifers, ...
  • Deuterostomia: chordates (vertebrates, sea squirts, ...), echinoderms (starfish, sea urchins, ...), ...

Metazoa: animals
  • Parahoxozoa: bilaterians, cnidarians (sea anemones, jellyfish, ...), placozoans (small blob animals)
  • Porifera (sea sponges)
  • Ctenophora (comb jellies)

Amorphea
  • Amoebozoa (amoebas)
  • Opisthokonta
    • Fungi
    • Choanoza: choanoflagellates (collar flagllates), metazoa (animals)

Archaeplastida:
  • Viridiplantae: Chlorophyta (some green algae), Streptophyta (some green algae, land plants)
  • Rhodophyta (red algae)
  • Glauophyta

SAR
  • Stramenopiles: oomycete "fungi", diatoms, kelp, ...
  • lAlveolata: ciliates, dinoflagellates, apicomplexans (malaria bug, ...)
  • Rhizaria: foraminferans, radiolarians

Diphoda / Bikonts
  • Diaphoretickes: Archaeplastida, SAR
  • Discoba: (Euglena, ...)

Eukarya: Diphoda, Amorphea

I've mentioned some one-celled eukaryotes, but I'm leaving out numerous others for brevity. It is evident that all of the deeper branchings in eukaryotedom are among one-celled organisms, with inventions of multicellularity scattered over this family tree.

So the ancestral eukaryote was a one-celled organism.
 
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Turning to prokaryotes, their deepest branching is the Bacteria-Archaea split, discovered in the mid-1970's. But no deeper branching has been discovered in the half-century since that time.

In Bacteria, there is a deep branching between Terrabacteria and Hydrobacteria, along with a few early branchers.

Terrabacteria include bacteria adapted to survive dryness, and also cyanobacteria, "blue-green algae". This suggests that ancestors of these bacteria had colonized land some 3 billion years ago. A good way to survive dryness is to have a thick cell wall, and that cell wall takes up the Gram stain, making them "Gram positive". Another way is to feverishly repair one's genome, what Deinococcus radiodurans does. That ability gave it the ability to survive doses of ionizing radiation that would kill most other organisms, what it was originally discovered to do.

Hydrobacteria are not so well-adapted to surviving dryness. They include enteric bacteria like Escherichia coli and Salmonella, and numerous others.
 
The last bacterial common ancestor (LBCA):
Not very much on the last archaeal common ancestor (LACA), however.

The last universal common ancestor (LUCA):
The LBCA and the LACA were much like the LUCA: anaerobic, lithotrophic, and autotrophic. Anaerobic? It neither released oxygen nor used O2, and it was likely poisoned by O2. Lithotrophic? Getting its energy from inorganic compounds like CO2 and H2. Autotrophic? Making all its biomolecules from simple precursors, like a plant.

There are present-day organisms much like the LUCA: methanogens. But the LUCA likely released acetic acid instead of methane, making them acetogens.

CO2 + 4H2 -> CH4 + 2H2O -- methane
2CO2 + 4H2 -> CH3COOH + 2H2O -- acetic acid, the vinegar acid

The LUCA was a full-scale organism, with a DNA genome, RNA in various functions, and proteins also in various functions. It made messenger RNA from DNA, and proteins from messenger RNA using ribosomes and transfer RNA.

It had a variety of cofactors for a variety of reactions, including B vitamins and several transition-metal ions.

It had a cell membrane and a cell wall, and a mixture of archeal (terpene) and bacterial (fatty-acid) membrane lipids. It could talerate salt, at roughly the present ocean concentration of it, and it liked high temperatures, as much as 70 C or more.

It had chemiosmotic energy metabolism, pumping hydrogen ions out of its cell interior and letting them back in to assemble ATP molecules at ATP synthase protein complexes.

In biochemistry, hydrogen ions are usually called protons, even though some of them are deuterons, about 1.45*10^(-4) of the total.

The LUCA and LACA were likely ovoid in shape, and the LBCA rod-shaped, and all three likely had a flagellum for moving around.

So the LUCA was a complicated organism, comparable to present-day free-living prokaryotes like methanogens.
 
The LUCA was thus far from the first self-replicating system, whatever it might have been. Going back further has the problem of having only one surviving descendant until one reaches the LUCA, an organism with two descendants, the ancestors of Archaea and Bacteria, and eventually of Eukarya.

It had DNA, RNA, and protein, and how much can we simplify from there?

In organisms, DNA is exclusively for carrying genetic information, serving as a master copy, a reference copy, a source copy, an original copy.

However, RNA not only carries genetic information, it helps assemble proteins. In fact, the major working parts of ribosomes, protein-assembly workbenches, are RNA molecules. Part of this assembly involves amino acids, protein building blocks, attached to transfer RNA's. The genetic information itself is copied onto more RNA, some messenger RNA, rather than being used in original DNA form.

Some cofactors also contain bits of RNA, at least in their active forms: riboflavin (B2), niacin (B3), pantothenic acid (B5), cobalamin (B12), and some have a nucleobase-like carbon-nitrogen ring structure: thiamine (B1), folic acid (B9), pyridoxine (B6) (?).

RNA also shows up in the energy intermediate ATP, a RNA building block with extra phosphates. Cyclic AMP, with the phosphate attached to two places on the ribose, is involved in signaling inside of cells.

RNA can also act as an enzyme - a ribozyme - and some of them are known in organisms, where they are often involved in splicing messenger RNA. Several ribozymes have been made in labs.

DNA can act as a similar sort of enzyme - a deoxyribozyme - but such enzymes have only been made in labs.
 
So RNA does lots of things, while DNA does only one thing.

Let us turn to their biosynthesis. We find that DNA building blocks are made from RNA ones. First, ribonucleotide-reductase enzymes turn ribose into deoxyribose, making uracil-DNA building blocks, then the uracil is converted to thymine by adding a methyl group to each one.

So DNA is a modification of RNA.

That leaves us with RNA and proteins.

Has anyone ever come up with a plausible way for proteins to transmit their sequence information to other proteins? I've yet to see anyone propose a plausible way of doing so. But nucleic acids have a simple method for doing so, one that they actually use.

171-4356indd.indd - WatsonCrick1953.pdf - "A Structure for Deoxyribose Nucleic Acid" - James Watson, Francis Crick - Nature, 1953

They proposed a structure of DNA where the deoxyribose-phosphate backbone chains are on the outside and the nucleobases on the inside, and paired with each other. They noted that

"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
 
The RNA-to-protein translation mechanism has as its central working parts RNA molecules, with proteins mainly structural material. So it was likely originally all RNA, with proteins added later.

The lost language of the RNA World - PMC
The possibility of an RNA World is based on the notion that life on Earth passed through a primitive phase without proteins, at a time when all genomes and enzymes were composed of ribonucleic acid. Numerous apparent vestiges of this ancient RNA World remain today, including many nucleotide-derived coenzymes, self-processing ribozymes, metabolite-binding riboswitches, and even ribosomes. Intriguingly, many of the most common signaling molecules and second messengers used by modern organisms are also formed from RNA. For example, nucleotide derivatives such as cAMP, ppGpp, and ZTP, as well as the cyclic dinucleotides c-di-GMP and c-di-AMP, are intimately involved in signaling diverse physiological or metabolic changes in bacteria and other organisms. Herein we describe the potential diversity of this ‘lost language’ of the RNA World, and speculate on whether additional components of this ancient communication machinery might remain hidden though still very much relevant to modern cells.
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Coenzymes as fossils of an earlier metabolic state - PubMed
A metabolic system composed of nucleic acid enzymes is proposed to have existed prior to the evolution of ribosomal protein synthesis. Vestiges of these nucleic acid enzymes persist in contemporary coenzymes. This proposal rationalizes the fact that many coenzymes are nucleotides or heterocyclic bases which could be derived from nucleotides.
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Modern metabolism as a palimpsest of the RNA world. - PMC
An approach is developed for constructing models of ancient organisms using data from metabolic pathways, genetic organization, chemical structure, and enzymatic reaction mechanisms found in contemporary organisms. This approach is illustrated by a partial reconstruction of a model for the "breakthrough organism," the last organism to use RNA as the sole genetically encoded biological catalyst. As reconstructed here, this organism had a complex metabolism that included dehydrogenations, transmethylations, carbon-carbon bond-forming reactions, and an energy metabolism based on phosphate esters. Furthermore, the breakthrough organism probably used DNA to store genetic information, biosynthesized porphyrins, and used terpenes as its major lipid component. This model differs significantly from prevailing models based primarily on genetic data.
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 Cofactor (biochemistry) - "Cofactors can be classified into two types: inorganic ions and complex organic molecules called coenzymes" - including several B vitamins.
 
untitled - Cold Spring Harb Perspect Biol-2012-Robertson-a003608.pdf - The Origins of the RNA World - Michael P. Robertson and Gerald F. Joyce
The general notion of an “RNA World” is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA and genetically encoded proteins were not involved as catalysts. There is now strong evidence indicating that an RNA World did indeed exist before DNA- and protein-based life. However, arguments regarding whether life on Earth began with RNA are more tenuous. It might be imagined that all of the components of RNA were available in some prebiotic pool, and that these components assembled into replicating, evolving polynucleotides without the prior existence of any evolved macromolecules. A thorough consideration of this “RNA-first” view of the origin of life must reconcile concerns regarding the intractable mixtures that are obtained in experiments designed to simulate the chemistry of the primitive Earth. Perhaps these concerns will eventually be resolved, and recent experimental findings provide some reason for optimism. However, the problem of the origin of the RNA World is far from being solved, and it is fruitful to consider the alternative possibility that RNA was preceded by some other replicating, evolving molecule, just as DNA and proteins were preceded by RNA.
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Arguing that RNA likely had a predecessor, because it's difficult to make its building blocks prebiotically.

Phosphate ions are, of course, prebiotic, and it's possible to make nucleobases prebiotically, especially adenine. But ribose is a different story. It's very difficult to make mainly ribose by some plausible prebiotic mechanism.
he classical prebiotic synthesis of sugars is by the polymerization of formaldehyde (the “formose” reaction). It yields a very complex mixture of products including only a small proportion of ribose (Mizuno and Weiss 1974). This reaction does not provide a reasonable route to the ribonucleotides. However, a number of more recent experimental findings, to some extent, address this deficiency.
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So there is a gap between prebiotic synthesis and the RNA world.
 
bilby said:
Shadowy Man said:
The point is that your statement is essentially empty rhetoric and has little if any probative value.
Click to expand...
It has exactly the same value as the claim that as gold can be created by the neutron bombardment of mercury, all gold was created by the neutron bombardment of mercury, and that gold is therefore an artificial element and doesn't occur naturally.

That is, his statement is essentially nonsense.
Click to expand...
Nitpick: Isn't all gold created by neutron bombardment? What other realistic process exists to create atoms past iron?
 
Loren Pechtel said:
bilby said:
Shadowy Man said:
The point is that your statement is essentially empty rhetoric and has little if any probative value.
Click to expand...
It has exactly the same value as the claim that as gold can be created by the neutron bombardment of mercury, all gold was created by the neutron bombardment of mercury, and that gold is therefore an artificial element and doesn't occur naturally.

That is, his statement is essentially nonsense.
Click to expand...
Nitpick: Isn't all gold created by neutron bombardment? What other realistic process exists to create atoms past iron?
Click to expand...
Nitpick: Terrestrial neutron bombardment of mercury produces only radioactive isotopes of gold. You can't get a high enough neutron flux to make stable gold, even in a supernova; To make gold-197 (the only stable isotope) requires neutron star collisions with free neutron densities sufficient to add multiple neutrons in very rapid succession (called the "r-process").

https://kaw.wallenberg.org/en/research/how-are-heavy-elements-formed-neutron-star-collisions
 
bilby said:
Loren Pechtel said:
bilby said:
Shadowy Man said:
The point is that your statement is essentially empty rhetoric and has little if any probative value.
Click to expand...
It has exactly the same value as the claim that as gold can be created by the neutron bombardment of mercury, all gold was created by the neutron bombardment of mercury, and that gold is therefore an artificial element and doesn't occur naturally.

That is, his statement is essentially nonsense.
Click to expand...
Nitpick: Isn't all gold created by neutron bombardment? What other realistic process exists to create atoms past iron?
Click to expand...
Nitpick: Terrestrial neutron bombardment of mercury produces only radioactive isotopes of gold. You can't get a high enough neutron flux to make stable gold, even in a supernova; To make gold-197 (the only stable isotope) requires neutron star collisions with free neutron densities sufficient to add multiple neutrons in very rapid succession (called the "r-process").

https://kaw.wallenberg.org/en/research/how-are-heavy-elements-formed-neutron-star-collisions
Click to expand...
Sure, but isn't it true that only a god can smack neutron stars together?
 
bilby said:
Loren Pechtel said:
bilby said:
Shadowy Man said:
The point is that your statement is essentially empty rhetoric and has little if any probative value.
Click to expand...
It has exactly the same value as the claim that as gold can be created by the neutron bombardment of mercury, all gold was created by the neutron bombardment of mercury, and that gold is therefore an artificial element and doesn't occur naturally.

That is, his statement is essentially nonsense.
Click to expand...
Nitpick: Isn't all gold created by neutron bombardment? What other realistic process exists to create atoms past iron?
Click to expand...
Nitpick: Terrestrial neutron bombardment of mercury produces only radioactive isotopes of gold. You can't get a high enough neutron flux to make stable gold, even in a supernova; To make gold-197 (the only stable isotope) requires neutron star collisions with free neutron densities sufficient to add multiple neutrons in very rapid succession (called the "r-process").

https://kaw.wallenberg.org/en/research/how-are-heavy-elements-formed-neutron-star-collisions
Click to expand...
I didn't realize there was no s-process path to gold. That would explain it's rarity.
 
Tracing gold’s cosmic origin story | PNAS - astronomers are sure that it's a r-process element, though they are not sure about the amount of relative contribution of Type II supernovae and neutron-star mergers.

The Nucleosynthesis of Gold - has a plot of the contributions of the two processes.
  • s-process: slow irradiation with neutrons: allows plenty of time for a nucleus with too many neutrons to do a beta decay, converting a neutron into a proton.
  • r-process: rapid iradiation with neutrons: no time for such decays until after the irradiation ends.
  • p-process: like the s-process, but with protons
  • rp-process: like the r-process, but with protons
 Nucleosynthesis with  File:Nucleosynthesis_periodic_table.svg derived from Origin of the elements

 Abundance of the chemical elements and  Abundances of the elements (data page)] and  Abundance of elements in Earth's crust

Earth biochemistry primarily depends on these six elements - H, C, N, O, P, S - and also utilizes numerous metal-ion cofactors:  Metalloprotein

Mg, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, Mo, Cd, W

Background metal ions

Na, K

Of these, only H was made in the early Universe. All the rest were made in massive stars, and most of these by nuclear fusion. That process reaches its limit at Fe and nearby, with the s-process and r-process continuing.

The origin of the elements isn't much of a problem for the origin of life, and not forming sufficient quantities of C, N, O, P, and S would also mean not forming sufficient raw materials for making Earthlike planets.
  • Water: H, O
  • Rocky material: O, Mg, Si
  • Iron cores: Fe, Ni
 
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