Looking for university/graduate-level texts on RNA

Although I was not a biology major in college, I took the biology introduction sequence, as well as organic chemistry and biochemistry.

I would like to learn more about RNA and ribozymes. What texts/textbooks are currently used? Perhaps it's best to begin with a genetics textbook.

The scope of the book should cover be at a undergraduate level or higher, and should cover the dynamics and purpose of ribozymes.

As suggested by others, you can start with some basics on molecular biology. Genes - Benjamin Lewin and Molecular Biology of the Gene - James Watson et al. are good books for the basics.

I haven't seen any book dedicated to RNA-biology and most of my understanding has come from reviews.

You can start by studying RNA secondary (and higher order) structures which is essential for understanding how riboswitches function. I would suggest that you first begin with the wikipedia article on this (it is not that great). The above-mentioned books would also cover the basics. You may then have a look at this review which is about thermodynamic and kinetic aspects of RNA-hairpins:

Structures, Kinetics, Thermodynamics, and Biological Functions of RNA Hairpins

For Riboswitches you can refer to these reviews, which are quite comprehensive:

  • Ribozymes, riboswitches and beyond: regulation of gene expression without proteins
  • Riboswitches: Emerging Themes in RNA Structure and function

This is another comprehensive review on ribozymes:

Ribozyme Structures and Mechanisms

PS: Some of these articles may not be freely available. You can mail the corresponding author (email address would be mentioned in the article) requesting for a reprint.

Looking for university/graduate-level texts on RNA - Biology

Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid (DNA) are nucleic acids. Along with lipids, proteins, and carbohydrates, nucleic acids constitute one of the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA, RNA is found in nature as a single strand folded onto itself, rather than a paired double strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information (using the nitrogenous bases of guanine, uracil, adenine, and cytosine, denoted by the letters G, U, A, and C) that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

Some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these active processes is protein synthesis, a universal function in which RNA molecules direct the synthesis of proteins on ribosomes. This process uses transfer RNA (tRNA) molecules to deliver amino acids to the ribosome, where ribosomal RNA (rRNA) then links amino acids together to form coded proteins.

Focus Area: Synthetic Biology

Synthetic biology uses methods and techniques from various disciplines such as molecular biology, organic chemistry and nanobiotechnology to design and construct new biological systems as well as to redesign and enhance existing ones. The applications range from the design of novel microbial strains for the production of biofuels and organic compounds to biosensors and biomedical applications all the way to creating artificial cells. In this focus area we have assembled our articles in this exciting area of research, some of which were published in the special issues Synthetic Cells and Gene Editing and Synthetic Biology.

Germ cell granules

Morphological descriptions of RNA granules originated with Metschnikoff (1865), who described dark staining granules at one pole within Miastor metraloas (fly) larvae. Subsequent studies showed that “polar granules” define sites of primordial germ cell differentiation in a variety of insect species (Ritter, 1890 Hegner, 1914). Analogous structures called germinal granules in Xenopus laevis, polar granules in Drosophila melanogaster, and P granules in Caenorhabditis elegans (here collectively referred to as germ cell granules [GCGs]) are RNP particles containing maternal mRNA that is required for germ cell specification (Schisa et al., 2001 Leatherman and Jongens, 2003). GCGs direct the timing of maternal mRNA translation to promote germ cell development in the early embryo and establish the germ line for the next generation. Germ cells contain other granules that may harbor translationally silenced mRNAs important for the development of other early embryonic tissues (Navarro and Blackwell, 2005). In addition to polyadenylated maternal transcripts (Schisa et al., 2001), GCGs contain proteins that regulate mRNA translation/decay, including the following: (1) multiple RNA-binding proteins, several of which are essential for both GCG structure and germ cell development (Fig. 1 Johnstone and Lasko, 2001) (2) CAR-1, an Sm protein related to Lsm proteins that regulate mRNA splicing, decapping, and decay (3) CGH-1, an RNA helicase that is related to Dhh1 and p54/Rck, enzymes involved in translational silencing and decapping (4) DCP1, a decapping enzyme and (5) orthologues of the translation initiation factors eIF4E and eIF5A. Thus, GCGs contain proteins involved in translation initiation, translation control, and mRNA decay, which is consistent with their proposed role in the regulation ofs maternal mRNA expression.

7.00x Introduction to Biology or similar (undergraduate biochemistry, molecular biology, and genetics), 7.28.1x and 7.28.2x Molecular Biology or similar (advanced understanding of the central dogma)

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About this course

In Part 3 of 7.28x, you’ll explore translation of mRNA to protein, a key part of the central dogma of biology. Do you know how RNA turnover or RNA splicing affects the outcome of translation? Although not official steps in the central dogma, the mechanisms of RNA processing strongly influence gene expression.

Are you ready to go beyond the “what" of scientific information presented in textbooks and explore how scientists deduce the details of these molecular models?

Take a behind-the-scenes look at modern molecular biology, from the classic experimental events that identified the proteins and elements involved in translation and RNA splicing to cutting-edge assays that apply the power of genome sequencing. Do you feel confident in your ability to design molecular biology experiments and interpret data from them? We've designed the assessments in this course to build your experimental design and data analysis skills.

Let’s explore the limits of our current knowledge about the translation machinery and mechanisms of RNA turnover and splicing. If you are up for the challenge, join us in 7.28.3x Molecular Biology: RNA Processing and Translation.

What you'll learn

  • How to compare and contrast translation in bacteria and eukaryotes
  • How to describe several mechanisms of RNA turnover and RNA splicing
  • How to analyze protein structures to infer functional information
  • How to design the best experiment to test a hypothesis
  • How to interpret data from translation and RNA processing experiments


Week 1: Translation I – Overview and Key Players
Week 2: Translation II – Elongation
Week 3: Translation III – Initiation and Termination
Week 4: Translation IV – Regulation of Translation
Week 5: RNA Splicing I – Mechanisms
Week 6: RNA Splicing II – Proofreading and Alternative Splicing
Week 7: RNA Turnover I – Assays and General Mechanisms
Week 8: RNA Turnover II – Specific Bacterial and Eukaryotic Mechanisms


ISMB/ECCB 2021 scientific program is poised to enlighten all. Click on the track areas to learn more about the science that will be presented July 25-30. Registered participants will be able to build personalized schedules within the virtual platform.

What is ISMB and Why Attend?

The ISMB/ECCB conference alliance has become synonymous with collaboration, fostering fresh dialogue, and providing inumerable learning opportunities. Moving the conference to a state of the art virtual interface will not change what attendees have come to expect from this conference. The virtual interface will only enhance the attendee experience and ensure that more of you can enjoy it.

Here is what to expect in the virtual environment:

  • Training workshops and tutorials
  • Student Council Symposium
  • Live and on-demand sessions to benefit attendees from all time zones
  • 500+ expected scientific talks
  • Live question and answer feature to engage with the speaker during sessions
  • Live chat feature to engage with other participants within your session room
  • Dedicated time for research presentation within the Research Exchange Forum (formerly Poster Hall)
  • Ability to serendipitously make new connections when utilizing the attendee profile and match maker features
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  • Exclusive access to the ISMB/ECCB 2021 on-demand repository of talks and poster presentations for viewing at your leisure after conference dates

Though we realize nothing replaces trying to run across a convention center between sessions, ISCB is making every effort to create a virtual experience that mirrors an in-person experience with less sore feet at the end of the day. Opportunities to present your research are still available.

Thank you for your continued support of ISCB and ECCB, and we look forward to “seeing” you in July for ISMB/ECCB 2021, the premier virtual event of the year!

Cell biology: The new cell anatomy

A menagerie of intriguing cell structures, some long-neglected and others newly discovered, is keeping biologists glued to their microscopes.

In 2008, Chalongrat Noree faced an unenviable task: manually surveying hundreds of yeast strains under a microscope. Each strain had a different protein tagged with a fluorescent label, and Noree, a graduate student at the University of California, San Diego, was looking for interesting structures in the cells.

But it wasn't long until Noree's labour yielded results: within a month, he began finding a wide variety of proteins assembling into clusters or long strands. “Imagine every week you found a new intracellular structure,” says Jim Wilhelm, a cell biologist and Noree's adviser. “If it were a slot machine, it would be paying off every other time you pulled the handle.”

These days, textbook diagrams of cell structures such as the nucleus, mitochondrion, ribosome and Golgi apparatus are beginning to seem out of date. New imaging techniques, genome data, interest from disciplines outside cell biology and a bit of serendipity are drawing attention to an intricate landscape of tubes, sacs, clumps, strands and capsules that may be involved in everything from intercellular communication to metabolic efficiency. Some could even be harnessed for use in drug delivery or in synthesis of industrial products, such as biofuels.

Some of these structures have been known for decades, whereas others have only recently come to light. Wilhelm's team, for instance, has found six kinds of filament that either had never been described, or had been largely passed over. “You figure, how many structures could have been missed in the cell?” says Wilhelm. “Apparently, a lot more than you would imagine.”

Lines of communication

One structure that is receiving fresh scrutiny is the membrane nanotube: a thin thread of membrane suspended between cells. In 2000, Amin Rustom, then a graduate student at Heidelberg University in Germany, was using a newly acquired dye to look at rat tumour cells under a fluorescence microscope. But he decided to skip some washing steps in the protocol. “He said, 'I saw something — I don't know what it is, but it looks interesting',” recalls his former adviser, Hans-Hermann Gerdes, a cell biologist now at the University of Bergen in Norway. The tubes that Rustom had noticed were so straight that Gerdes initially wondered if they were scratches on the dish.

The team concluded in a 2004 study 1 that the structures, which could span the distance of several cells, were channels that could transport small cellular organelles. That same year, Daniel Davis, a molecular immunologist at Imperial College London, and his colleagues proposed that immune cells might send signals to each other along such tubes 2 . At the time, Davis recalls, “There would always be people in the audience who would say, 'I saw those strands in the late 1970s or 80s'.” But earlier observers paid little heed to the tubes.

The 2004 reports prompted more studies, which have found nanotubes in many types of mammalian cell. Davis's team found that nanotubes could help certain white blood cells to kill cancer cells, either by acting as a tether that draws the cancer cell close or by providing a conduit for delivering lethal signals 3 . Nanotubes can also conduct electrical signals, which might enable cells to coordinate during migration or wound healing, according to a 2010 study by Gerdes and his colleagues 4 . HIV and prions — infectious, misfolded proteins — may even travel along the tubes 5,6 .

Some researchers are sceptical that nanotubes can form open channels. “It's not clear that there's a real continuous tunnel,” says Jennifer Lippincott-Schwartz, a cell biologist at the US National Institutes of Health in Bethesda, Maryland. And so far, nanotubes have been studied mainly in cell culture. Blocking nanotube formation in living organisms might give clues to their importance, says Davis. But such manipulations often disturb other crucial processes.

Productivity hotspots

Researchers have long puzzled over how some metabolic processes work so efficiently. If the proteins involved are not close together, intermediate molecules could get lost in the “bewildering mass of enzymes in the cell”, says Stephen Benkovic, a chemical biologist at Pennsylvania State University in University Park. Proteins often assemble to carry out a particular task — a large complex is required to copy DNA, for example — but Benkovic and others have wondered whether metabolic enzymes might cluster together in a multistep assembly line, passing sometimes-unstable molecules from one 'worker' to the next.

Benkovic's group found evidence that this clustering does occur in enzymes that produce a precursor of purine nucleotides, which are components of DNA and RNA. The team tagged each enzyme with a fluorescent label and observed them in living cells under the microscope. When a cell was deprived of purines, the enzymes grouped together in a cluster, which the team called the 'purinosome' 7 . Last year, the team reported that purinosomes are nestled in a mesh of protein fibres called microtubules, like berries in a bramble bush 8 . The molecules produced by purinosomes can be converted to the cellular fuel adenosine triphosphate, so Benkovic speculates that purinosomes may help power the transport of organelles and materials around the cell on microtubule tracks.

Edward Marcotte, a systems biologist at the University of Texas at Austin, advises caution in interpreting these results, however. He and his colleagues have seen enzyme clusters as well: in 2009, they reported that they had found 180 types of protein forming clumps in starved yeast cells 9 . But it is not clear whether the clumps serve a useful purpose — such as improving metabolic efficiency or acting as storage depots — or are a result of cellular failures brought on by starvation, says Marcotte.

Some researchers are taking a closer look at elegant bacterial protein containers called microcompartments. First seen about 50 years ago, these polyhedron-shaped protein capsules resemble the outer shell of a virus 10 . But unlike viruses, which package genetic material, microcompartments contain enzymes that carry out important reactions, such as converting carbon dioxide into a form of carbon that is usable by the cell. Scientists suspect that the shells make reactions more efficient, keep toxic intermediate products away from the rest of the cell and protect enzymes from molecules that could hinder their performance.

In 2005, protein crystallographers helped to reveal the capsules' finer details. Microcompartments “simply hadn't attracted the attention yet of structural biologists”, says Todd Yeates, a structural biologist himself at the University of California, Los Angeles. He and his colleagues found that some shell proteins assemble into six-sided tiles that come together to form the sides of a microcompartment 11 . Each tile has a hole in the centre that could allow molecules to pass through.

In addition to having an orderly structure, microcompartments can also line up in neat rows. Pamela Silver, a synthetic biologist at Harvard Medical School in Boston, Massachusetts, and her colleagues reported 12 last year that in cyanobacteria, certain microcompartments called carboxysomes “more or less stayed in a line down the centre of the cell”, says Silver. This tidy arrangement allows cells to allot carboxysomes evenly to daughter cells when dividing.

Biologists are now eager to exploit these capsules for industrial uses by loading them with different enzymes. For instance, Yeates and his team are planning to try engineering microcompartments to produce biofuel. Some researchers have managed to package fluorescent proteins or enzymes from other species into the shells, suggesting that it is possible to modify the capsules' contents.

Microcompartments still offer plenty of unexplored territory. Scientists aren't sure, for instance, exactly how enzymes are organized inside the capsules, says Cheryl Kerfeld, a structural biologist at Lawrence Berkeley National Laboratory in Berkeley, California. “We don't really know what it looks like in there.”

Other subcellular packages drawing attention are exosomes — tiny membrane-enclosed sacs that form inside the cell and are later spat out. These nanoscale vessels were discovered in the 1980s and then ignored for about a decade — considered a way of bagging up cellular rubbish. “People thought they were junk, basically,” says Jan Lötvall, a clinical allergist at the University of Gothenburg in Sweden.

Interest in exosomes picked up in 1996, when Graça Raposo, a cell biologist now at the Curie Institute and the National Centre for Scientific Research in Paris, and her colleagues scrutinized exosomes spat out by B cells, a type of white blood cell. Although the technology to examine them — electron microscopy — wasn't new, it wasn't very popular at the time because “it was just old-fashioned”, says Raposo. Using it and other techniques, the team reported that the humble vessels might do something useful: display scraps of pathogen protein on their surfaces, spurring immune cells to mount defences against an infection 13 . Scientists became even more intrigued when Lötvall's team reported in 2007 that exosomes could carry messenger RNA 14 , some of which could be picked up and translated in a recipient cell. This suggested that the shipments might allow cells to affect protein production in their neighbours. The study “really showed that exosomes were a vehicle of communicating important information between cells”, says Clotilde Théry, a cell biologist who is also at the Curie Institute.

Researchers are now trying to use exosomes to deliver drugs to specific parts of the body — with the hope that, because exosomes are 'natural', they might be less likely to be toxic or provoke an immune response than other vessels, such as artificial lipid sacs or protein shells. This year, Matthew Wood, a neuroscientist at the University of Oxford, UK, and his colleagues reported 15 an attempt in mice: the team loaded exosomes with artificial RNA intended to hinder production of a protein involved in Alzheimer's disease and tagged them with a molecule directing them to neurons and the blood–brain barrier. The exosomes successfully delivered their cargo and reduced production of the protein with no obvious ill effects, the team found. Other scientists are trying to fish exosomes out of body fluids and analyse their contents to diagnose cancer or deploy exosomes to provoke immune responses against tumours.

Finally, Wilhelm's group and others have found filaments that string together enzymes by the hundreds or thousands — enough, in some cases, to span nearly the entire cell. One of the filament-forming enzymes Wilhelm's team found was CTP synthase, which makes a building block for DNA and RNA 16 . Two other teams discovered the same filaments in fruitflies and bacteria at around the same time 17,18 . One researcher, Ji-Long Liu, a cell biologist at the Medical Research Council Functional Genomics Unit at the University of Oxford, named them cytoophidia (or 'cell serpents') because of their snake-like shapes in fly cells. Wilhelm suspects that researchers found the same filaments in the 1980s but never identified the protein.

These structures could allow the cell to turn enzymes on and off en masse, suggests Wilhelm. For instance, if the enzymes in a filament are inactive, the cell could activate all of them by dissolving the strand.

In some bacteria, enzyme filaments also seem to serve a structural purpose, somewhat like the actin filaments that are part of the cytoskeleton in more complex cells. When Zemer Gitai, a cell biologist at Princeton University in New Jersey, and his colleagues studied the structures in a comma-shaped bacterium called Caulobacter crescentus, they found that CTP-synthase filaments kept the cells' curvature in check. If there was too little of the enzyme, the cells curled up tightly if there was too much, they straightened out 18 .

It is not clear why curvature is important for the bacterium, says Gitai, but the findings suggest that the cells may have co-opted enzyme filaments to preserve cell shape. Researchers already suspect that actin is related to the enzyme hexokinase. It is possible that the cytoskeleton arose from filaments that originally formed to regulate the cell's metabolism, Gitai says.

Although the purpose and importance of some of these emerging structures is not yet clear, the research illustrates that the act of simply observing cells and their contents is alive and well. “A key aspect of doing great science is exploration,” says Davis. “I think that there's a tremendous amount that we learn just by watching.”


Biotechnology, Second Edition approaches modern biotechnology from a molecular basis, which has grown out of increasing biochemical understanding of genetics and physiology. Using straightforward, less-technical jargon, Clark and Pazdernik introduce each chapter with basic concepts that develop into more specific and detailed applications. This up-to-date text covers a wide realm of topics including forensics, bioethics, and nanobiotechnology using colorful illustrations and concise applications. In addition, the book integrates recent, relevant primary research articles for each chapter, which are presented on an accompanying website. The articles demonstrate key concepts or applications of the concepts presented in the chapter, which allows the reader to see how the foundational knowledge in this textbook bridges into primary research. This book helps readers understand what molecular biotechnology actually is as a scientific discipline, how research in this area is conducted, and how this technology may impact the future.

Biotechnology, Second Edition approaches modern biotechnology from a molecular basis, which has grown out of increasing biochemical understanding of genetics and physiology. Using straightforward, less-technical jargon, Clark and Pazdernik introduce each chapter with basic concepts that develop into more specific and detailed applications. This up-to-date text covers a wide realm of topics including forensics, bioethics, and nanobiotechnology using colorful illustrations and concise applications. In addition, the book integrates recent, relevant primary research articles for each chapter, which are presented on an accompanying website. The articles demonstrate key concepts or applications of the concepts presented in the chapter, which allows the reader to see how the foundational knowledge in this textbook bridges into primary research. This book helps readers understand what molecular biotechnology actually is as a scientific discipline, how research in this area is conducted, and how this technology may impact the future.

Label: Protein Synthesis

In the past, I have used Transcription Coloring to reinforce the concept of the central dogma, as it shows how DNA is converted to RNA which travels to the ribosomes where a protein is created from individual amino acids carried on transfer RNA.

This coloring worksheet does not work well for remote learners during the 2020 pandemic, so I created this drag-and-drop alternative where students can label the images. There are three slides on this activity, the first two show images of the process and the last slide asks students to answer text questions that describe various parts of the process. For example: “What is the role of tRNA in the process?”

Students can also practice with this worksheet on the Genetics of Sickle Cell Disease which goes into greater detail about the relationship between the proteins and functions of those proteins. A single switch in a base, can lead to the nonfunctional protein found in hemoglobin. There is also a labeling handout that is similar but is designed for students to do on paper, in class.

Author’s contributions

Reviewer 1: Jerzy Jurka, Genetics Information Institute

This is a straightforward paper exploring important implications of prion-mediated heredity for the Central Dogma.

I have only some minor comments:

It would be useful to quote the article Alain E. Bussard on the same subject [75], and to highlight the major new arguments introduced in the current article.

Author’s response: Bussard’s article appears to be something of a misnomer in that the author puts the Central Dogma in the title but does not really examine it with respect to the properites of prions. His article instead explores the Lamarckian features of the prion inheritance and certainly is of interest for its historical aspects.

I believe that the author should also comment on RNA editing in the “look-ahead” section e.g. [76].

Author’s response: This comment is appreciated, an interesting point is brought up here. Although as far as RNA editing or transcriptional errors are involved, the actual mutating entity is RNA rather than protein, the net effect on heredity is the same as with translation errors. Effectively, a version of the look-ahead effect indeed could be engendered by RNA editing, with stochastic editing creating variation that can be subsequently fixed in the genome through convergent genetic variation. I included a statement to that effect in the revised version of the manuscript. The same pertains to errors of transcription. Unfortunately, the report of extensive editing by Li et al.[76]has been compromised to such an extent[77–79]that it has become difficult to interpret these observations.

Finally, I recommend including the article by Sergey G. Inge-Vechtomov et al. [16], that includes a unique historical perspective on “non-inherent variability” dating back to Kirpichnikov.

Author’s response: I cited the article by Inge-Vechtomov et al. as a review but my reading again is that this is about protein-based heredity not violations of the Central Dogma.

Reviewer 2: Pierre Pontarotti, Universités de Provence et de la Méditerranée

In this review/outlook, the author studied the assumption that the information could be originated from protein to protein and from phenotypes to DNA. The author also highlighted that “violation of the central dogma” and the “epigenetics trans generational inheritance” are two different phenomena, even if sometime, they could be connected. Although this point seems to be obvious, this clarification is essential (I meet several scientists mixing the two concepts). In my opinion, I think that the main question asked by the author: “Does the central dogma still stand?” is opportune. Investigators really need to transgress scientific dogmas. But we will still need to propose robust approaches to test new hypotheses.

Reviewer 3: Juergen Brosius, University of Muenster

The author questions the Central Dogma of Molecular Biology, because structural modification of prion-like proteins might have a (more global) effect on the expression and even structure of gene products. The idea is based on data obtained with studies of yeast prion-like proteins, for example, the Sup35 protein that normally acts as a translation termination factor. However, when sequestered in amyloid, hence insoluble and inactive, its deficiency allows for readthrough of termination codons in messenger RNAs.

The author places such strategies of increasing evolvability into the category of quasi-Lamarckian evolution. Like most phenomena in biology, similarity to the Lamarckian mode of evolution lies somewhere on a continuum ranging from barely apparent to very strong. In my opinion, the possible elongation of polypeptides is at the very weak end of the continuum of Lamarckian mode of evolution, not too remote from random mutations of nucleotides, since this process is almost equally non-directed.

Author’s response: I am not going to strongly argue this point. Thea ‘quasi-Lamarckian’ mechanisms certainly belong to the continuum of evolutionary phenomena, from stochastic to deterministic ones[67]. The Lamarckian character of this readthrough is not the focus of the present article which is about information transfer from protein to genome the readthrough seems to capacitate such transfer.

In addition, most S. cerevisiae 3′-UTRs tend to be short, typically in the size range of 50 to 200 nucleotides, with a median length of 121 nt [80]. Should a C-terminal ORF extension truly be part of a ‘look ahead effect’ [50] for times of stress, might one not observe distal to the bona fide stop codons a slightly higher conservation of the first two positions in the respective codons?

Author’s response: This is a really, really interesting idea. Yes, in principle, one should expect some degree of purifying selection in the sequences downstream of stop codons. However, because readthrough is not frequent, the effect could be quite weak so that its detection would require sophisticated statistical analysis of large data sets. To the best of my knowledge, no one has shown that such conservation does not exist (a difficult task as well). This seems to be well worth investigating.

Furthermore, messenger RNAs transcribed from genes containing mutations that generate aberrant extended 3′ untranslated regions are degraded by nonsense mediated decay (NMD) [81–83]. Even if NMD was suppressed by an additional stress induced mechanism, the C-termini of proteins usually are the least conserved parts of a protein and often can be altered or extended without functional consequences [84]. Once more, the action of prions apparently do not have an effect on their own expression or C-terminal extension. Due to this undirected nature, I would place prion formation to the weak end of the continuum concerning quasi-Lamarckian mode of evolution. Something similar could be said about modification of nucleic acids, most prominently methylation of DNA in control regions of genes, as this process seems to be not specifically directed. However should the link between prenatal nutrient deprivation in humans and adiposity in later life - in conjunction with the findings that reduced methylation of the insulin like growth factor II gene (IGF2) is the underlying molecular mechanism for this effect – become substantiated, at least some of these epigenetic effects due to methylation changes could be placed closer to the opposite end of the continuum [85–87]. Animal studies will be essential to rigorously test these observations initially made in human populations. The case of the prokaryotic CRISPR-cas system of defense against mobile elements including plasmids and viruses is an interesting and much stronger case as covered by the author in a previous publication [67]. Nevertheless, a stochastic event and not the need for viral defense lead to integration and antisense transcription of part of the invader’s genome. The fortuitous beneficiary effect of, e.g., antiviral protection was of selective advantage and became fixed. As mentioned in the review of this Koonin/Wolf article, in my view, the examples that most closely resemble Lamarckism or quasi-Lamarckism stem from several ongoing transitions in our own lineage, namely vertical and horizontal transmission of memes [88, 89] and at the level of genes through our potential (not yet realized) to direct acquired knowledge about genotype/phenotype relationships into our own genome in a precise and specific manner via genetic engineering [90–92].

Author’s response: These comments are appreciated. I find memetics to be of much interest and promise. However, in my view, this field of enquiry is outside evolutionary biology sensu strictu.

The Central Dogma of Molecular Biology is, in my opinion, still untouched as there is no reverse translation. This would change if a mutation in a given protein including a translational readthrough beyond the stop codon directly would lead to a nucleotide change that converts said stop codon into one that encodes an amino acid. My own problem with the Central Dogma of Molecular Biology is different, more trivial, and based on the depiction of DNA and not RNA topping the hierarchy [93].

Author’s response: This is a key conceptual point that is addressed in the main text of the present article but is worth pondering again. True, to the best of our knowledge, there is no reverse translation but this is not what the Central Dogma is about. Quoting Crick[1]: ‘The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred back from protein to either protein or nucleic acid.’ So Crick was fully explicit in formulating the Central Dogma as a ‘law’ of information transfer in biological systems not as a statement about specific reaction paths. It is remarkable that, although evolution failed to find ways to reverse transcription, it has found means to circumvent this irreversibility through completely different mechanism, and so after all, to reverse the direction of the information flow. As for the “more trivial” aspect, it is certainly indisputable that the diversity of RNA roles in biology, in particular in shaping genomes via retrotransposition, was vastly under-appreciated 40 years ago (and might not be fully appreciated yet).

Watch the video: I Asked Bill Gates Whats The Next Crisis? (January 2022).