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Root of the Tree: The Significance, Evolution, and Origins of the Ribosome.

The paper having the title of this post is here: Root of the Tree: The Significance, Evolution, and Origins of the Ribosome (Jessica C. Bowman, Anton S. Petrov, Moran Frenkel-Pinter, Petar I. Penev, and Loren Dean Williams, Chem. Rev. 2020, 120, 11, 4848–4878)

I go through a number of scientific papers in the course of a day, but seldom am I inspired to read any in their entirety. I just go to the "good parts" and most often leave unimportant details out. (I'm the same with books; but recently, in the age of Covid and the cloture of libraries, I find myself reading some books cover to cover.) I almost never read a journal issue cover to cover, but I may find myself inspired to read one now. The current issue of Chemical Reviews is devoted largely to Scientific Reviews of the origin of life, a subject that has fascinated me ever since my high school biology teacher described the Miller Urey experiment. I didn't know doodley squat about chirality then, but nevertheless, the interest in the prebiotic origins - and for that matter the abiotic origin of chirality - have fascinated me during my long life. What better time is there to muse on the origins of life as one's own life winds down. I hope I find and have the time to read this issue in its entirety.

This particular paper is really striking, inasmuch as it touches on the key structure at the interface of the two main classes of molecules that have been the subject of speculation as the originating molecules, peptides/proteins/amino acids and nucleic acids: The ribosome.

This is a very long paper, and I can only excerpt a tiny portion, but if one finds a way to these papers, and one is interested in this mysterious topic, "why and how life?," one may find some fascinating discussion.

All cells contain ribosomes, the cellular structures that translate DNA/RNA into the proteins that basically run life's machinery. (Thomas Cech and others found that RNA can also catalyze molecular transitions.)

The partnership between RNA and protein dominates biology. The durability of this ancient partnership is documented in the universal tree of life (TOL), which is the lineage of the translation system. Woese and Fo1,2) sketched out a universal TOL revealing the blueprint of the common origins and biochemical interrelatedness of all living systems. This TOL contains three primary branches, which are the bacterial, archaeal, and eukaryotic superkingdoms of life. More recent determinations of the TOL, using concatenated sequences of ribosomal proteins (rProteins), increased the resolution and accuracy of the tree.(3,4) TOLs now incorporate reconstructed genomes of unculturable organisms from a variety of environments.(5,6) In the most recent TOLs, eukarya branches from within archaea.(6,7) The last universal common ancestor of life (LUCA) lies at the first branch point of the TOL. Extant biology is the crown. The origin of life occurred within the root of the TOL. As a system to organize and frame vast amounts of information, the TOL is on par with the Periodic Table.

The ribosome, made from RNA and protein, is responsible for synthesizing all protein in living systems. The ribosome is composed of a small ribosomal subunit (SSU) that decodes mRNA and a large ribosomal subunit (LSU) that catalyzes peptidyl transfer. To make a protein, the ribosome initiates, interprets an mRNA codon (decodes), transfers an amino acid from a tRNA to a nascent peptide, translocates, repeats the last three of these steps over and over again, and ultimately terminates synthesis at an mRNA stop codon.(8−12) In Bacteria, new peptide bonds are formed at a rate of ∼20 amino acid additions per second. The functional core of the SSU is the decoding center (DCC) and the functional core of the LSU is the peptidyl transferase center (PTC). The distribution of ribosomal functions within rRNA secondary structures is shown in Figure 1. Aminoacyl-tRNA synthetases (aaRSs) enforce the genetic code by joining amino acids to their cognate tRNAs...

...2.1. Universality of the Ribosome

Genes encoding the translation machinery dominate the universal gene set of life (UGSL),(13−15) which is the set of protein-encoding genes that are shared as orthologues throughout the TOL and are found in essentially every living system. Koonin’s version of the UGSL contains around 65 genes.(14) Fifty-three of these are directly involved in translation, including 34 genes for rProteins (Figure 2) and genes for aaRSs and translation factors. The Pace(13) and Doolittle(15) versions of the UGSL are very similar to that of Koonin. The USGL is larger and even more translation-centric if it is expanded to include nontranslated genes such as those encoding rRNAs and tRNAs. A few constituents of the USGL are involved in transcription and even fewer in replication. There are no genes for metabolism, membrane biosynthesis or proton pumps in the UGSL.

The universality of translation across living systems extends beyond sequence homology to three-dimensional structures. Ribosomal and other translational components are universal in three-dimensions for all living systems (Figures 3, 4, and 5).(17−20) The extreme structural conservation of the DCC and the PTC(21−23) is illustrated in Figure 3. All ribosomes, from large bacterial to even larger archaeal ribosomes to gigantic mammalian ribosomes, are built upon the same basal structure, which we call the universal common core. The universal common core has a mass of nearly 2 million Daltons.(18,19)...

The point of the review is the understanding that this structure, the ribosome, is rather universal and is thus an essential point to consider in the origins of life.

Now I'll share some "science porn" with the captions...

The caption:
Figure 1. Functional regions of rRNA. (a) Information mapped onto the E. coli SSU rRNA secondary structure. CPK indicates the central pseudoknot; FPK is the functional pseudoknot. (b) Information mapped onto the E. coli LSU rRNA secondary structure. A plurality of LSU rRNA is assigned to the exit tunnel (cyan), indicating that it performs a principal function of the LSU. The second shell of the exit tunnel provides buttressing for the first shell of the exit tunnel. Regions of multiple function, for example, rRNA that contributes to both the A-site and the PTC, are striped with two colors. Strand termini and select helices are indicated. Domains are indicated on the SSU rRNA. Domains are not indicated on the LSU rRNA where they have no physical significance. Interactions with ribosomal proteins are not included.

The caption:
Figure 2. The Tree of Life mapped with universal and superkingdom-specific ribosomal proteins. The line width of the TOL is weighted by the total number of rProteins in a given superkingdom. Universal rProteins are listed in white text in the black region at the bottom. Bacteria-specific rProteins are in the blue region on the right, and Archaea-specific rProteins are in the lime-green region in the center. Eukarya-specific rProteins are in the red region on the left. All Archaea-specific rProteins are found in Eukarya, and thus, no rProteins are unique to Archaea. This rProtein nomenclature is consistent with the TOL; rProteins in Eukarya that are of archaeal ancestry are labeled as archaeal. This rProtein naming scheme, by incorporating evolutionary relationships into rProtein names, is intended to facilitate understanding of the evolution of the translation system. Adapted with permission from ref (16), where a dictionary of various rProtein naming schemes can be found.

The caption:
Figure 4. The universal common core of rRNA mapped onto the secondary and three-dimensional structures of rRNAs of a bacterium and an archaeon. The SSU (left) contains the 16S rRNA and the LSU (right) contains the 23S and 5S rRNAs. Red (SSU) and blue (LSU) indicate common core rRNA. Black or gray indicate rRNA that is not part of the common core and is variable in structure or absent from some species. (a) The rRNA of the bacterium E. coli. (b) The rRNA of the archaeon P. furiosus. Some sites of insertion of microexpansion segments are indicated by dashed lines in the archaeon secondary structure. Each three-dimensional structure is viewed from the solvent exposed surface of the assembled ribosome, with the subunit interface directed into the page. E. coli, PDB 4V9D, and P. furiosus, PDB 4V6U. Adapted with permission from ref (19).

The caption:
Figure 5. The universal common core mapped onto the secondary and three-dimensional structures of rRNAs of the eukaryote S. cerevisiae. The SSU (left) contains the 18S rRNA, and the LSU (right) contains the 26S, 5.8S, and 5S rRNAs. Red (SSU) and blue (LSU) indicate common core rRNA, as in the previous figure. Some sites of insertion of expansion segments are indicated by dashed lines. S. cerevisiae: PDB 4V88. Adapted with permission from ref (19).

And where bugs like us fit in to this key:

The caption:
Figure 11. Secondary structures of ES7 mapped onto the canonical eukaryotic TOL. Colors indicate the extent of conservation of ES7 rRNA. Blue is Helix 25, part of the universal common core. Green rRNA is universal to all eukaryotes except those with reduced genomes. Yellow is universal to metazoans. Red is tentacle rRNA. Tentacles reach extreme lengths in birds and mammals.

And how all this life might have arisen from simplicity:

The caption:
Figure 17. The coevolution of LSU rRNA, SSU rRNA, tRNA, and proteins. Six phases of the accretion model lead to the LUCA ribosome. In phase 1, RNAs form stem-loops and minihelices that begin to accrete. In phase 2, the PTC is formed and catalyzes condensation in the absence of coding. The SSU may have a single-stranded RNA binding function. In phase 3, the subunits gain mass. At the end of phase 3, the interface is acquired and the subunits associate, mediated by the expansion of tRNA from a minihelix to the modern L-shape. LSU and SSU evolution is independent and uncorrelated during phases 1–3. In phase 4, evolution of the subunits is correlated. The ribosome is a noncoding diffusive ribozyme in which proto-mRNA and the SSU act as positioning cofactors. In phase 5, the ribosome expands to an energy-driven, translocating, decoding machine. In phase 6, the ribosome matures, marking completion of the common core with a proteinized surface (the proteins are omitted for clarity). The colors of the rRNA and rProtein phases are the same as in Figures 13c,d, and 15. mRNA is shown in light green. The A-site tRNA is magenta, the P-site tRNA is cyan, and the E-site tRNA is dark green. Adapted with permission from ref (114).

A little beauty on a beautiful day.

I wish you a pleasant, safe, and healthy afternoon.

Vaccines that use human fetal cells draw fire

In case, at this late date, you had any doubt that the right wing is far more interested in fertilized eggs than it is in living breathing humans, adults and children, there's this news item from this week's issue of Science: Vaccines that use human fetal cells draw fire. (Meredith Wadman, Science, June 12, 2020, Vol. 368, Issue 6496, pp. 1170-1171) It appears to be open sourced.

Some excerpts:

Senior Catholic leaders in the United States and Canada, along with other antiabortion groups, are raising ethical objections to promising COVID-19 vaccine candidates that are manufactured using cells derived from human fetuses electively aborted decades ago. They have not sought to block government funding for the vaccines, which include two candidate vaccines that the Trump administration plans to support with an investment of up to $1.7 billion, as well as a third candidate made by a Chinese company in collaboration with Canada's National Research Council (NRC). But they are urging funders and policymakers to ensure that companies develop other vaccines that do not rely on human fetal cell lines and, in the United States, asking the government to “incentivize” firms to make only vaccines that don't rely on fetal cells...

...Now, research groups around the world are working to develop more than 130 candidate vaccines against COVID-19, according to the World Health Organization. At least six of those candidates use one of two human fetal cell lines: HEK-293, a kidney cell line widely used in research and industry that comes from a fetus aborted in about 1972; and PER. C6, a proprietary cell line owned by Janssen, a subsidiary of Johnson & Johnson, developed from retinal cells from an 18-week-old fetus aborted in 1985. Both cell lines were developed in the lab of molecular biologist Alex van der Eb at Leiden University.

Two of the six vaccines have entered human trials (see table, below). Five are made by using human fetal cells as “factories” to make adenoviruses that carry genes from SARS-CoV-2, the virus that causes COVID-19...

It's OK, though, to put babies in cages after they're born. There has been no announcement as to whether it will prove "ethical" to use cell lines from babies in cages after they die. Probably, the same people carrying on about the fetal cells from 1972 couldn't care less about those babies, because they were already born, and lost protection from the self declared "ethics" mavens, the minute they took air into their lungs.

Coronavirus rips through Dutch mink farms, triggering culls

I found this news item in the scientific journal Science, a publication of the AAAS. I didn't need to log in to my subscription to read it, so it's open sourced. It's here: Coronavirus rips through Dutch mink farms, triggering culls (M Enserink, Science, Vol. 368, Issue 6496, pp. 1169)

Some excerpts:

In a sad sideshow to the COVID-19 pandemic, authorities in the Netherlands began to gas tens of thousands of mink on 6 June, most of them pups born only weeks ago. SARS-CoV-2 has attacked farms that raise the animals for fur, and the Dutch government worries infected mink could become a viral reservoir that could cause new outbreaks in humans.

The mink outbreaks are “spillover” from the human pandemic—a zoonosis in reverse that has offered scientists in the Netherlands a unique chance to study how the virus jumps between species and burns through large animal populations.

But they're also a public health problem. Genetic and epidemiological sleuthing has shown that at least two farm workers have caught the virus from mink—the only patients anywhere known to have become infected by animals. SARS-CoV-2 can infect other animals, including cats, dogs, tigers, hamsters, ferrets, and macaques, but there are no known cases of transmission from these species back into the human population. (The virus originally spread to humans from an as-yet-unidentified animal species.)...

...That mink are susceptible wasn't a surprise, because they are closely related to ferrets, says Wim van der Poel of Wageningen University & Research, which has an animal health laboratory here. (Both mink and ferrets can also contract human influenza viruses.) Like humans, infected mink can show no symptoms, or develop severe problems, including pneumonia...

...The Dutch outbreaks are giving scientists a chance to study how the virus adapts as it spreads through a large, dense population. In some other animal viruses, such conditions trigger an evolution toward a more virulent form, because the virus isn't penalized if it kills a host animal quickly as long as it can easily jump to the next one....

The virus has yet to infect mink farms in that offshore oil and gas drilling hellhole, Denmark.

It appears that the Dutch have given mink farmers a few more years before requiring them to shut down on animal cruelty grounds.

Be safe, be well.

Spectacularly Ethical Young People.

I've been reading about the Theranos scandal, which should have been obviously fraudulent for anyone who knew anything about clinical chemistry. These young people knew something about clinical chemistry and acted:

When I see people like this - one of them George Schultz's grandson - I feel better for the future:

The Death of a Street Performer, Margaret Holloway, the 'Shakespeare Lady' of New Haven

This NY Times article moved me, because many years ago I lost a very wonderful housemate, a very talented singer, and when lucid, a great friend, to mental illness, when, in a schizophrenic episode, he jumped off a bridge named for his uncle.

It's good to remember than the victims of Covid are not just numbers, but people

Margaret Holloway, the ‘Shakespeare Lady’ of New Haven, Dies at 68

A once-promising director and actor who struggled with mental illness and drug addiction, she performed for years on the city’s streets. She died of Covid-19.

This obituary is part of a series about people who have died in the coronavirus pandemic. Read about others here.

On the streets of New Haven, Conn., Margaret Holloway was known as the “Shakespeare Lady,” a tall, striking woman in ragged clothing who recited dramatic monologues for spare change.

Her stage, often, was outside Willoughby’s coffee shop, a hangout for Yale students and professionals. Her repertoire included “The Tempest,” “Macbeth” and the Greek alphabet, which she acted out letter by letter.

Many regarded Ms. Holloway as an eccentric local fixture; in the view of some business owners, however, she was an aggressive panhandler and public nuisance. But for those who knew her personal history, her life had tragic dimensions not unlike the material she performed.

Ms. Holloway was a 1980 graduate of the Yale School of Drama and a once-promising director, playwright and actor. In the early 1970s she was a drama major at Bennington College in Vermont...

...Ms. Holloway’s career was cut short by mental illness and drug addiction soon after she left Yale. But she never stopped seeking understanding, human connection and, above all, artistic expression.

Correlation of Prevalence of Corona Virus in Sewage with Disease Prevalence in the Netherlands.

The paper to which I'll refer in this post is this one: Presence of SARS-Coronavirus-2 RNA in Sewage and Correlation with Reported COVID-19 Prevalence in the Early Stage of the Epidemic in The Netherlands. (Gertjan Medema, Leo Heijnen, Goffe Elsinga, Ronald Italiaander, and Anke Brouwer, Environ. Sci. Tech Letters, ASAP June 2020.) It is available as an "as soon as possible" publication and has just been published on line. Like most Covid related scientific papers, this one, provided by the American Chemical Society, of which I am a proud member, is open sourced.

A note: It is well known that some active diseases, for example, polio, can be carried by sewage effluent. My late mother-in-law, one of the last polio victims in the United States, before wide use of the vaccine, contracted the disease after a trip a beach. This paper does not make the claim that this is a mode of transmission, but is rather intended to use an indirect method, the presence of viral RNA in sewage as an estimate of the prevalence of the disease.

From the opening text:

In December 2019, an outbreak of coronavirus respiratory disease (called COVID-19) was detected in Wuhan, China. The outbreak was caused by a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak is now widespread, and WHO declared a pandemic on March 11, 2020, when the disease was reported in 114 countries.(1) The primary mode of transmission of SARS-Cov-2 is via respiratory droplets that people produce when they cough, sneeze, or exhale, and the virus may also be spread via fomites.(2) SARS-CoV-2 is 82% similar to the SARS coronavirus that caused an outbreak in 2003. Then, 16%–73% of patients with SARS were reported to have diarrhea in addition to respiratory symptoms,(3) and transmission of SARS through water droplets from faeces via air ventilation systems in Amoy Gardens in Hong Kong was reported.(4) Diarrhea is also reported in a significant proportion of the COVID-19 cases, and recent reports show that SARS-CoV-2 has been detected in stool samples of COVID-19 cases.(5−9) The shedding of SARS-CoV-2 was studied in a cluster of nine cases and was present at 107 RNA copies/stool swab of a gram faeces one week after symptom onset and decreased to 103 RNA copies/swab three weeks after symptom onset.(10) These authors could not detect infectious SARS-CoV-2 in stool samples with high RNA concentrations. Another study(11) reported that in two out of four stool samples with high SARS-CoV-2 RNA concentrations, infective SARS-CoV-2 was detected with cultures combined with electron microscopy. Although it is unlikely that wastewater will become an important transmission pathway for coronaviruses like SARS-CoV-2,(12) increasing circulation of the virus in the population will increase the virus load into the sewer systems of our cities.

A graphic from the paper:

The caption:

Figure 1. Cumulative prevalence of reported COVID-19 cases in the cities that are served by the WWTP from February 27–March 29, 2020.

The full text of the paper, which is again, available, is useful for anyone who is interested in the technology for tracking this sort of thing. Details of the procedure may be found by clicking on the "Supporting Information" link in the paper.

The interesting paper's conclusion:

The testing policy in The Netherlands focused on people with a travel history to Hubei or Italy, people with severe symptoms, and healthcare workers. A study among healthcare workers in The Netherlands indicated that SARS-CoV-2 was already circulating undetected in the community a week prior to February 27, when the first COVID-19 case was reported, suggesting that there is a high prevalence of mild COVID-19 in the community.(25) Recent serological surveys in The Netherlands and elsewhere show that the percentage of people that have been infected with COVID-19 is much higher than reported through clinical surveillance and is in the range of 1%–14%.(26) While absolute estimates of COVID-19 prevalence based on SARS-CoV-2 RNA concentrations in sewage are complex, our data suggest that surveillance of relative changes in SARS-CoV-2 RNA concentrations at the inlet of WWTP over time can serve as a sensitive tool for early warning for increasing virus circulation in the population.

Be safe and healthy.

Chicago Tribune: Joe Biden Isn't Behaving Presidentially.


As an astute observer of present-day presidential politics, I’m baffled by the way presumptive Democratic presidential nominee Joe Biden is behaving.

The most immediate example, of course, is that he spent time Monday traveling to Texas to meet in person with the family of George Floyd. He was the black man killed by a white Minneapolis police officer, setting off nationwide protests over police brutality and racism.

What kind of modern-day leader shows empathy during a time of national crisis? If Biden had an ounce of presidential timber he would have been in a secure location, surrounded by armed guards and newly erected fencing, tweeting about his own “GREATNESS” and calling his political opponents “Crazy!”

Even worse, Biden has yet to tweet the words “LAW & ORDER” accompanied by no specific context or policy proposals. Donald Trump, our current president and the model for cutting-edge presidential behavior, has tweeted those words a dozen times in the past week. That, former Vice President Biden, is a thing we Americans have come to recognize as “leadership.” Maybe try it some time.

Indeed, while Biden spent time meeting privately Monday with Floyd’s family before the 46-year-old man’s funeral in Texas, he failed to label Americans exercising their right to protest as “thugs” or “terrorists.” He didn’t attempt to paint people appalled by systemic racism as part of a shadowy group known as antifa, which isn’t actually an organized group but sounds scary and is probably coming to destroy your family farm or rage-stomp your begonias...

The full text is pretty good I think...

Randy Rainbow's Latest: The Bunker Boy.

I don't know if it's been posted already, but Randy Rainbow's the Bunker Boy is one of the best of the best:

So for those of you who watch it, what are they covering over at Fox News...a tulip show, perhaps?

Never mind. I really don't want to know.

Has anyone heard from Trump's pet puppy, Lindsay Graham, who likes the word "lynching" on this topic

I would suppose that he has no objection to crushing a man's larynx; as opposed to the awful, terrible lynching the House put forth against the orange maniac.
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