Posts Tagged ‘proteins’
abiogenesis – some amateur explorations
woteva
One of the greatest mysteries and challenges we face, as living beings – if we’re interested – is how living beings came to be. And we’re the only form of living beings, that we know of, asking this question. Hans Castorp, the central character of Thomas Mann’s The Magic Mountain, pondered the matter in his loggia while taking the cure in an alpine sanatorium. He even went further than the What is life question, asking What is matter? Why is there something rather than nothing?
It was a novel that changed my life. From that reading experience I turned, quite abruptly, to science. I bought Scientific American every month, until I switched to New Scientist, and started reading books by Richard Dawkins, Peter Atkins et al. Of course I’ve never undertaken any formal studies in science, and I’ve always preferred the informal to the formal, and not being subject to authorities telling me what to learn or know. That’s why Hans Castorp, reading and musing in his loggia, so appealed to me.
So what do we know on this subject? When did life begin on Earth, and how? It could have been close to 4 billion years ago, only half a billion years(!) after our planet was fully formed. We don’t have solid evidence, though. The earliest accepted evidence goes back 3.5 billion years, of ‘bacteria-like organisms’. That sounds pretty complex already, and presumably the ‘ingredients’, the intracellular material that sustained and motivated these beings, were around long before. Complexifying chains of molecules, formed out of the ‘primordial soup’, to use an unhelpful term. We think RNA and DNA of course, or at least nucleic acid chains. But what are nucleic acids, and what are the parts thereof? Other essential components include proteins and lipids, with the latter being essential to create more or less permeable boundaries between the organic and the inorganic (or proto-organic?). Lipid molecules, as the Arvin Ash video referenced below tells us, consist of a hydrophilic body, of sorts, and a hydrophobic tail. These molecules tend to come together to form spheres, with the outer, bulkier, hydrophilic ends joining together to protect or insulate the hydrophobic tails from the watery outer environment.
So there’s always a ‘what came before’ question. Where did these lipid molecules spring from, not to mention the other bits and bobs of life? Well, on lipids, I’m relying, for now, on the same video. Carbon monoxide (CO), hydrogen and minerals found in the Earth’s crust can combine to form lipids. All of these components can be found in the hydrothermal vents so recently found in the Pacific depths. But lipid structures break down in the presence of salt or magnesium ions, and these ions are essential for cellular and RNA development. Big problem, as the primeval oceans are believed to be more salty than those of today – though apparently we’re far from being certain about this. In any case, a 2019 paper from the University of Washington showed that lipid spheres remained intact in the presence of amino acids, the building blocks of protein molecules. To quote from the video,
The enclosing of amino acids within cell walls allows them to concentrate within those walls and interact with each other to form proteins, which are part of the ‘trinity’, one of the essential components of life.
So lipid cell walls and proteins, both of course non-living, require each other to survive in salty or iron-rich water. But what about the nucleic acids, DNA and RNA? These are the self-replicating molecules, the genetic material, or precursor genetic material. Today we know that RNA is created from DNA to build proteins according to DNA’s code, but the fact that RNA is the simpler of the two genetic materials suggests to most analysts that it came first. So there’s a hypothesis called the ‘RNA world’, which is generally well accepted by those in the field, but unfortunately we’ve made little progress in working out how RNA came to be formed.
RNA is made up of three chemical components – ribose (a sugar), the nucleobases, and phosphate. A ribose-base-phosphate unit links with other such units to form RNA polymer. But it’s not well understood how these links were formed, and they haven’t been successfully replicated in human experiments. The ribose-base link has proved particularly problematic. As Arvin Ash describes it, ‘this is because cells in your body require complex enzymes to bring RNA building blocks together before they combine to form polymers’. He describes one study, however, which found that today’s RNA could have formed on the surface of clays ‘which act like a catalyst to bring RNA bases together’. A later study showed that the building blocks of RNA could have polymerised in the early Earth, using organic molecules from meteorites and interplanetary dust in shallow ponds, where wet/dry cycles would have been conducive to such polymerisation. They considered that these polymers were probably present on Earth shortly after its formation.
So Ash describes a trinity – RNA, lipids and proteins. What about the proteins? We can go back to the Miller-Urey experiments of the 1950s, which showed that amino acids, the essential components of proteins, as well as other organic compounds, could be produced under particular atmospheric conditions, which they were able to replicate in the laboratory.
So, all these precursors might be explained, but they still need to combine for life as we know it, however basic. This is the big question that still needs to be answered. We haven’t discovered any precise mechanism, but oodles of time, and incremental steps are probably required, and there is surely a possibility of this in the first billions of our planet’s existence, wherein trillions of molecular interactions may have taken place. It’s something of a numbers game, something that many earlier theorists, and today’s creationists, have not taken sufficient account of. It’s also probable that the earliest life forms, those sparks, were so basic that they were quickly improved upon and rendered obsolete by – evolution. But that’s another story…
Needless to say, this piece was more or less wholly reliant on Arvin Ash’s excellent video, which I highly recommend.
References
Why is the Ocean So Salty?
introducing myself to abiogenesis, sort of
Yes, watch out for the creationists and their ultra ultra ultra male god…
So, more sciencey stuff by a non-scientist, this time on how life came about from non-life, and where exactly the boundary lies. I seem to recall, years ago, that Craig Venter, something of a maverick biochemist, or whatever, was competing with the ‘official’, i.e government-funded, program, to map the human genome, and it might’ve come out as a tie, but don’t quote me. And then Venter and Co went on to work on abiogenesis, and then I lost touch…
I was reminded of all this when I watched a video featuring a Christian fundamentalist and biochemist, James Tour (I keep thinking James Tool) and his fight with mainstream biochemists on the difficulty/impossibility of life coming from non-life, because, of course, God – or as Americans like to call him, Guard, because, as we know, Guard blesses America, and safeguards Him (because, as we know America is as fundamentally male as Guard) on an ongoing basis.
In googling Mr Tour, the first thing I came up with was ‘Is James Tour religious?’ The answer, of course, is another question – Do bears shit in the woods?
But let’s not get too lazy by mocking US silliness ad nauseam. In the video, Tour is shown violently lashing out at claims that there is any possible chemical pathway for something living – that’s to say self-sustaining – to have come from something purely chemical, no matter how complex. And yet, in spite of Tour’s noisy, over-the-top attacks on the whole abiogenesis program, presumably because it was ‘playing Guard’, in the end, when talking to a sympathetic and doubtless Christian interviewer, he admitted that we might one day work out the process that sparked life, in spite of its ‘infinite’ (or near-infinite) complexity, because, after all, Guard is infinite (or near-infinite?)….
I suspect he might regret that admission.
So, after all that, how are we going on the abiogenesis front? First, a little history. Spontaneous generation was once considered very much a thing, in the days before microscopes and such, and this is unsurprising, as I myself have seen maggots ‘suddenly’ infesting something rotting in a cupboard in my lazy house-sharing youth. Such situations caused considerable debate in earlier centuries, until better technologies and experiments, in particular the work of Louis Pasteur, finally disproved the concept. But this, of course, left a gap – if there was no spontaneous generation of life, and evolution by natural selection had nothing to say on the subject, then – maybe Guard? Or Guard of the Gap?
But enough of Guard, we already have complex collections of molecules, such as viruses, which seem to bridge the gap between life and non-life through their ability to replicate rapidly under particular conditions – but not independently. According to the RationalWiki on the subject:
Abiogenesis is not a single step event, but a process. Biological life has the properties or capabilities of organization, metabolism, homeostasis, growth, reproduction, response, and evolution.
So, it’s generally considered likely that abiogenesis cannot be sheeted home to one semi-miraculous event – more likely there were various combinatorial chemical developments that more or less succeeded in maintaining the above-mentioned properties. At some stage in this process, a stable life-form emerged that combined these ingredients effectively. This life-form has been dubbed the last universal common ancestor (LUCA).
Three elements appear to be essential – carbon, and hydrogen and oxygen in the form of water. The compounds focussed on by biochemists studying the subject are lipids, which can form membranes, carbohydrates, which can provide energy, amino acids, and nucleic acids (DNA and RNA) for reproduction.
I’m fairly clueless, so I’ll start with amino acids. Wikipedia tells me they’re essential for ‘protein metabolism’, but apparently not all amino acids are involved in this process – far from it. Of the more than 500 amino acids that we know to exist, there are only 22 that are ‘incorporated into proteins’ and into the genetic code of all life. They’re called proteinogenic amino acids, or α-amino acids (alpha amino acids).
But what exactly is an amino acid? Obviously it’s an acid, which we tend to think is something negative that breaks down and destroys stuff. But then amino makes me think of animation, in a scrambled sort of way. I mean, life? They are described as organic molecules, or organic compounds after all. Why? Apparently, for many biochemists an organic compound is one containing carbon. The proteinogenic amino acids are the ‘raw material’ assembled by our ribosomes (by the ribosomes of all living cells?) into the multitudinous peptides and proteins that do so much mysterious work throughout our bodies. I’m getting most of this from Wikipedia, a fantastic resource that just keeps getting fantasticker. It’s article on abiogenesis is itself virtually book-length, and the links take you to dozens of other useful and lengthy articles.
So how did amino acids come into being? Before ribosomes, the amino acid-making machines in our cells, came into being, that is. Well, first we needed the elemental ingredients, and they existed billions of years ago, at the Earth’s formation, and even before the Sun had coalesced into the star we know today. In a PubMed article abstract, ‘The origin of the biologically coded amino acids’ (that’s to say the proteinogenic ones), the problem/solution is put this way:
The types of amino acids produced depend on the conditions which prevailed at the time of synthesis, which remain controversial. The selection of the biological set is likely due to chemical and early biological evolution acting on the environmentally available compounds based on their chemical properties. Once life arose, selection would have proceeded based on the functional utility of amino acids coupled with their accessibility by primitive metabolism and their compatibility with other biochemical processes.
So, before there was biological evolution there was chemical evolution, which also may have been a matter of fits and starts. For example, some have speculated that carbonaceous meteorites raining down on the early Earth may have provided a spark, or a boost. These speculations are forward-looking from the non-living, in a sense, while another approach is backward-looking from known candidates for LUCA. Here’s how Wikipedia puts it:
It appears there are 60 proteins common to all life and 355 prokaryotic genes that trace to LUCA; their functions imply that the LUCA was anaerobic with the Wood–Ljungdahl pathway, deriving energy by chemiosmosis, and maintaining its hereditary material with DNA, the genetic code, and ribosomes. Although the LUCA lived over 4 billion years ago (4 Gya), researchers believe it was far from the first form of life. Earlier cells might have had a leaky membrane and been powered by a naturally occurring proton gradient near a deep-sea white smoker hydrothermal vent.
I won’t pretend I understand all that, but prokaryotes are unicellular organisms, and anaerobic respiration utilises ‘electron transport chains’ other than – and less efficient than – oxygen. The Wood-Ljungdahl pathway is, inter alia, a proposed mechanism – still controversial – for the anaerobic prokaryotic life found at deep sea alkaline hydrothermal vents, in the late 1970s.
The key problem, it seems to me, is that of effective replication, way back in the day. DNA and RNA are both very complex molecules, and so they didn’t just spring into existence. The Wikipedia article articulates the problem in a sentence that’s easy to simply overlook:
Prebiotic synthesis creates a range of simple organic compounds, which are assembled into polymers such as proteins and RNA.
We’re still quite a way from understanding that ‘assembly’ stage, though we’ve managed a bit of prebiotic synthesis, but there’s no reason to assume that we can’t work it all out. Now if we could find simple, perhaps differently-organised life or proto-life on other planets or moons…
That’s astrobiology, apparently. And Wikipedia can explain it all better than me, so excuse my laziness.
The 2015 NASA strategy on the origin of life aimed to solve the puzzle by identifying interactions, intermediary structures and functions, energy sources, and environmental factors that contributed to the diversity, selection, and replication of evolvable macromolecular systems, and mapping the chemical landscape of potential primordial informational polymers. The advent of polymers that could replicate, store genetic information, and exhibit properties subject to selection was, it suggested, most likely a critical step in the emergence of prebiotic chemical evolution. Those polymers derived, in turn, from simple organic compounds such as nucleobases, amino acids, and sugars that could have been formed by reactions in the environment. A successful theory of the origin of life must explain how all these chemicals came into being.
Hoping to write about this more in the future, exploring any new developments, if any.
References
https://rationalwiki.org/wiki/Abiogenesis
https://en.wikipedia.org/wiki/Abiogenesis
Interferons – they’re there to help
some human interferon looks something like this, according to someone
When I first heard of interferon (singular), I thought it was a drug, some sort of miracle drug being touted as a cure-all. I had no idea. Recently I’ve heard that it, or they, are part of our innate immune system, which is different from our adaptive immune system, though what the differences are I have no idea. Again. So, it’s learning time.
Wikipedia vastly increases my knowledge with its first sentence on interferons (duh, I wonder why people don’t use it more):
Interferons … are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.
Host cells are the cells of larger organisms (such as ourselves) that ‘host’, willingly or not, viruses and other bugs, or organelles, whatever. Signalling proteins are explained, somewhat, in the second quoted sentence.
Anyway, interferons belong to the larger class of proteins known as cytokines, which I’ve heard of in relation to the ‘cytokine storm’, a reaction or over-reaction to viruses such as SARS-Cov2, but they do more than just signal, they interfere, as the name suggests. In fact they have multiple functions, such as ‘upregulating antigen presentation’. An antigen, as I almost recall, is a molecular structure, part of a pathogen that can be bound by an antigen-specific antibody. Antigen presentation is – well it’s too complex to explain here, though I feel I need to arm myself with as much immunological knowledge as possible against the misinformation out there.
So IFNs, as they’re known, come in 3 types, alpha, beta and gamma, based on the receptors through which they signal. They form part of the innate immune system, generally speaking, but there are in fact complex interactions between the innate and adaptive immune systems which immunologists are still trying to work out. I should point out here that my first understanding of interferon was no doubt based on a breakthrough in the eighties when interferons were created in the lab to treat certain types of cancer, and later in the treatment of hepatitis, multiple sclerosis and other conditions, though many of these interferon medications have been superseded by newer treatments with fewer side-effects.
My question arose through watching a Medcram video – update 128 – ‘innate immunity, interferon and Covid-19 in children’. I’ve used these updates in the past to reduce my general ignorance of immunology, virology and the like, but I’ve not watched any for a while. So, having just perused the Wikipedia article on IFNs and finding it way too complex for my small brain, I’ll base the rest of this piece on Dr Seheult’s Medcram presentation.
So, the innate and adaptive immune systems are presented pictorially. The innate system starts with a myeloid progenitor cell. These cells are described in ScienceDirect as ‘the precursors of red blood cells, platelets, granulocytes…’ and a bunch of other cells. In the Medcram pictorial, arrows from the myeloid progenitor cell lead to five other cell types – mast cells, basophils, neutrophils, monocytes and eosinophils. Arrows from the monocytes then lead to macrophages and dendritic cells. What do these have to with IFNs? I’m trying to find out.
Mast cells are types of granulocyte, and they contain granules ‘rich in histamine [which induces inflammation] and heparin [which prevents blood clotting]’. They play an important protective role in the immune and neuroimmune systems.
Basophils are also granulocytes, and a type of white blood cell (leukocyte). They’re the rarest and largest type of granulocyte, and are an inflammatory agent.
A neutrophil is ‘a type of immune cell that is one of the first cell types to travel to the site of an infection. Neutrophils help fight infection by ingesting microorganisms and releasing enzymes that kill the microorganisms. A neutrophil is a type of white blood cell, a type of granulocyte, and a type of phagocyte’ (National Cancer Institute – USA).
Eusinophils ‘are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates’ (Wikipedia).
A monocyte is ‘a type of immune cell that is made in the bone marrow and travels through the blood to tissues in the body where it becomes a macrophage or a dendritic cell. Macrophages surround and kill microorganisms, ingest foreign material, remove dead cells, and boost immune responses. During inflammation, dendritic cells boost immune responses by showing antigens on their surface to other cells of the immune system. A monocyte is a type of white blood cell and a type of phagocyte’ (National Cancer Institute).
Now to return to the Medcram video, which tells me that the innate immune system includes macrophages and killer T cells (which are also part of the adaptive immune system). These combine to phagocytise, or ingest, viral or pathogenic material. This innate immune system is generally very strong in childhood and gets weaker with age. Interferon is a product of this innate system. Dr Seheult cites a recent article from Nature Biotechnology with the revealing title ‘Pre-activated antiviral innate immunity in the upper airways controls early SARS-Cov2 infection in children’. I’m fascinated with the idea of ‘pre-activated’ immunity here. As far as I know vaccines pre-activate immunity to viruses or pathogens by presenting the immune system with a part of that pathogen, or a protein unique to it. But with children, how is their immune system pre-activated? In any case, the article explains that ‘children displayed higher basal expression of relevant pattern recognition receptors [involving interferons] in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-Cov2 infection than in adults’. This finding highlights the importance of interferons and of perhaps trying to maintain their prevalence in older subjects. The article described children presenting in emergency with severe Covid19 as having an impaired IFN response, though the molecular mechanisms for this, and for the protective effects on those children with mild or no symptoms, were unknown.
So the article explains that higher levels of genes coding for RIG-1, MDA5 and LGP2 in the epithelial cells of the upper airways were found in children, but not in adults. RIG-1 is a pattern recognition receptor (PRR) of the innate immune system, responsible for type 1 interferon responses. MDA5 and LGP2 are members of the same family of PRRs. The key being more innate immune cells in that region in children, exhibiting strong antiviral action against SARS-Cov2. This is apparently what is meant by ‘pre-activated’, because these primed cells were already in the upper airways (i.e the nose) of children. However, there appears to be a narrow window of opportunity before viral reproduction, which is especially intense with SARS-Cov2, shuts down this innate immune response. The paradox, it seems here, is that SARS-Cov2’s proteins can effectively shut down interferon production, but at the same time the virus is highly sensitive to interferon. Anyway, it seems that if we can step up IFN production, assisting the body’s innate immune system, this may enable us to resist the virus (along with vaccination, effective mask wearing and physical distancing of course). One way to do this is by raising the core temperature of the body (inducing hyperthermia). At a core temp of 39 degrees celsius, the amount of IFN released from lymphocytes after mitogen stimulation (i.e inducing mitosis) increases ten-fold from just a degree or so below, at least in vitro. This may sound crazy, but the benefits of induced fever have been proven in various treatments for various infections, including viral infections, in the past, along with other ways of boosting the immune system (vitamin D, zinc and selenium) mentioned previously by Dr Seheult and other experts.
Science science science science science science. Don’t use social media to find out about SARS-Covid19 and its treatment. Never never never never. There are dozens of reputable scientific sites that will inform you, in the USA and in every other country – at least the WEIRD ones. Knowledge is power. Get informed.
References
https://en.wikipedia.org/wiki/Interferon
https://www.webmd.com/drug-medication/interferons-guide#1
Innate Immunity, Interferon, and COVID 19 in Children: Update 128 (video)
https://www.sciencedirect.com/topics/immunology-and-microbiology/myeloid-progenitor-cell
https://en.wikipedia.org/wiki/Mast_cell
https://www.healthline.com/health/basophils
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neutrophil
https://en.wikipedia.org/wiki/Eosinophil
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/monocyte
https://en.wikipedia.org/wiki/RIG-I
https://en.wikipedia.org/wiki/MDA5
https://en.wikipedia.org/wiki/Mitogen