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Nowadays, senescence and degenerative diseases sound like stupid design. But back then, they were important mechanisms to enforce genetic changes, hence opening the chance for genetic improvement.Even though harmful mutations have higher chance to occur than the beneficial ones, the risk can be countered by higher reproduction rate. But that means many individuals must be sacrificed to accumulate genetic improvements, which is not an efficient strategy.
CRISPR-Cas9 has made waves in the biomedical world as a revolutionary gene editing tool, even garnering a 2020 Nobel Prize in chemistry. But it has its limitations.A research team from the University of Illinois at Urbana-Champaign (UIUC) showed that another gene editing technique called TALEN is up to five times more efficient than CRISPR-Cas9 in a highly compact form of DNA called heterochromatin, according to results published in Nature Communications.The findings point to TALEN as a better option for the engineering of some hard-to-edit genomic regions, which could be applicable to both research and therapies, the scientists argued. Genetic defects in heterochromatin can cause such diseases as sickle cell anemia, beta thalassemia and fragile X syndrome.
An anthropologist dives into the world of genetic engineering to explore whether gene-editing tools such as CRISPR fulfill the hope of redesigning our species for the better.
Strictly speaking, we are all mutants. At a molecular level, each of us is unique. Each of us starts life with 40–80 new mutations that were not found in our parents. From birth, each of us has around 20 inactive genes from loss-of-function mutations. During the course of a normal human life, we also accumulate mutations in our bodies, even in our brains. By the time we reach age 60, a single skin cell will contain between 4,000 and 40,000 mutations, according to a study in the Proceedings of the National Academy of Sciences. These genetic changes are the result of mistakes made each time our DNA is copied during cell division or when cells are damaged by radiation, ultraviolet rays, or toxic chemicals. Generally, mutations aren’t good or bad, just different.
The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.Alexander Rich first proposed the concept of the RNA world in 1962, and Walter Gilbert coined the term in 1986. Alternative chemical paths to life have been proposed, and RNA-based life may not have been the first life to exist. Even so, the evidence for an RNA world is strong enough that the hypothesis has gained wide acceptance. The concurrent formation of all four RNA building blocks further strengthened the hypothesis.Like DNA, RNA can store and replicate genetic information; like protein enzymes, RNA enzymes (ribozymes) can catalyze (start or accelerate) chemical reactions that are critical for life. One of the most critical components of cells, the ribosome, is composed primarily of RNA. Ribonucleotide moieties in many coenzymes, such as acetyl-CoA, NADH, FADH, and F420, may be surviving remnants of covalently bound coenzymes in an RNA world.Although RNA is fragile, some ancient RNAs may have evolved the ability to methylate other RNAs to protect them.If the RNA world existed, it was probably followed by an age characterized by the evolution of ribonucleoproteins (RNP world), which in turn ushered in the era of DNA and longer proteins. DNA has better stability and durability than RNA; this may explain why it became the predominant information storage molecule. Protein enzymes may have come to replace RNA-based ribozymes as biocatalysts because their greater abundance and diversity of monomers makes them more versatile. As some co-factors contain both nucleotide and amino-acid characteristics, it may be that amino acids, peptides and finally proteins initially were co-factors for ribozymes.
The cells that make up all living things, despite their endless variations, contain three fundamental elements. There are molecules that encode information and can be copied—DNA and its simpler relative, RNA. There are proteins—workhorse molecules that perform important tasks. And encapsulating them all, there’s a membrane made from fatty acids. Go back far enough in time, before animals and plants and even bacteria existed, and you’d find that the precursor of all life—what scientists call a “protocell”—likely had this same trinity of parts: RNA and proteins, in a membrane. As the physicist Freeman Dyson once said, “Life began with little bags of garbage.”The bags—the membranes—were crucial. Without something to corral the other molecules, they would all just float away, diffusing into the world and achieving nothing. By concentrating them, membranes transformed an inanimate world of disordered chemicals into one teeming with redwoods and redstarts, elephants and E. coli, humans and hagfish. Life, at its core, is about creating compartments. And that’s much easier and much harder than it might seem.
First, the easy bit. Early cell membranes were built from fatty acids—molecules that look like lollipops, with round heads and long tails. The heads enjoy the company of water; the tails despise it. So, when placed in water, fatty acids self-assemble into hollow spheres, with the water-hating tails pointing inward and the water-loving heads on the surface. These spheres can enclose RNA and proteins, making protocells. Fatty acids, then, can automatically create the compartments that were necessary for life to emerge. It almost seems too good to be true.And it is, for two reasons. Life first arose in salty oceans, and salt catastrophically destabilizes the fatty-acid spheres. Also, certain ions, including magnesium and iron, cause the spheres to collapse, which is problematic since RNA—another key component of early protocells—requires these ions. How, then, could life possibly have arisen, when the compartments it needs are destroyed by the conditions in which it first emerged, and by the very ingredients it needs to thrive?Caitlin Cornell and Sarah Keller have an answer to this paradox. They’ve shown that the spheres can withstand both salt and magnesium ions, as long as they’re in the presence of amino acids—the simple molecules that are the building blocks of proteins. The little suns that Cornell saw under her microscope were mixtures of amino acids and fatty acids, holding their spherical shape in the presence of salt.
Scientists studying how life arose from the primordial soup have been too eager to clean up the clutter.Four billion years ago, the prebiotic Earth was a messy place, a chaotic mélange of diverse starting materials. Even so, certain key molecules still somehow managed to emerge from that chemical mayhem — RNA, DNA and proteins among them. But in the quest to understand how that happened, according to Ramanarayanan Krishnamurthy, a chemist at the Scripps Research Institute in California, researchers have been so myopic in their focus on reactions that generate molecules relevant to the planet’s current inhabitants that they’ve overlooked other possibilities.“They are trying to impose biology today on prebiotic chemistry,” he said. “But trying to make the final product right from the raw material — it misleads us.”
The narrative that has tantalized origin-of-life researchers for decades is the RNA world scenario: Pure RNA arose within the original prebiotic broth of molecules; the RNA made copies of itself but also later evolved and invented DNA as a more stable partner in replication; peptides joined the dance somewhere along the way. This theory has mainly been bolstered by the discovery that RNA can act both as a genetic material and as a catalyst, meaning it could have performed those roles early in life’s history and handed the baton over to DNA and proteins later on.But the RNA world isn’t a perfect solution. Perhaps the biggest stumbling block is that there have been serious problems with getting pure RNA to replicate itself sustainably in the laboratory. As a first step toward making a copy of itself, a single strand of RNA can take up complementary nucleotide building blocks from its surroundings and stitch them together. But the paired RNA strands then tend to bind to each other so tightly that they don’t unwind without help, which prevents them from acting as either catalysts or templates for further RNA strands.
“It’s a real challenge,” Sutherland said. “It’s held the field back for a long time.”But perhaps starting with a jumble of compounds instead of pure RNA alone could fix that, Krishnamurthy thought, after a 2016 experiment involving just such a melting pot yielded unexpected results.
“I think the RNA world was like an aphrodisiac for many people,” Krishnamurthy said. “It was like a fairy-tale ending: RNA was made and everyone lived happily ever after.” But now it’s becoming clear that “in prebiotic chemistry, you [should be] happy to work with mixtures, and you don’t have to find chemistry that will make only one particular molecule, which is unrealistic.”
Scientists have used genome sequencing and editing to develop a rapid-fire way to domesticate plants, allowing the quick transformation of wild rice into a bountiful crop.The common form of domesticated rice (Oryza sativa) has two copies of its genome in most cells, but some of its wild relatives have four — a feature that has been associated with vigorous and hardy plants. To take advantage of such genomic richness, Jiayang Li at the Chinese Academy of Sciences in Beijing and his colleagues developed a way to make precise changes to the genome of a wild species of rice called Oryza alta. Such precision genome editing is a challenging task in many plants.
The best process is no process. It weighs nothing, costs nothing, can't go wrong. So, as obvious as that sounds, the best part is no part. Elon Musk
Life with purposeBiologists balk at any talk of ‘goals’ or ‘intentions’ – but a bold new research agenda has put agency back on the table
One of biology’s most enduring dilemmas is how it dances around the issue at the core of such a description: agency, the ability of living entities to alter their environment (and themselves) with purpose to suit an agenda. Typically, discussions of goals and purposes in biology get respectably neutered with scare quotes: cells and bacteria aren’t really ‘trying’ to do anything, just as organisms don’t evolve ‘in order to’ achieve anything (such as running faster to improve their chances of survival). In the end, it’s all meant to boil down to genes and molecules, chemistry and physics – events unfolding with no aim or design, but that trick our narrative-obsessed minds into perceiving these things.Yet, on the contrary, we now have growing reasons to suspect that agency is a genuine natural phenomenon. Biology could stop being so coy about it if only we had a proper theory of how it arises. Unfortunately, no such thing currently exists, but there’s increasing optimism that a theory of agency can be found – and, moreover, that it’s not necessarily unique to living organisms. A grasp of just what it is that enables an entity to act as an autonomous agent, altering its behaviour and environment to achieve certain ends, should help reconcile biology to the troublesome notions of purpose and function.
But if we break down agency into its constituents, we can see how it might arise even in the absence of a mind that ‘thinks’, at least in the traditional sense. Agency stems from two ingredients: first, an ability to produce different responses to identical (or equivalent) stimuli, and second, to select between them in a goal-directed way. Neither of these capacities is unique to humans, nor to brains in general.
At the very least, the latest research suggests that it’s wrong to regard agency as just a curious byproduct of blind evolutionary forces. Nor should we believe that it’s an illusion produced by our tendency to project human attributes onto the world. Rather, agency appears to be an occasional, remarkable property of matter, and one we should feel comfortable invoking when offering causal explanations of what we’re observing.
Cogito ergo sum is the only naturally occuring connection between subjective and objective reality. The "ought world" only tells half story of subjective reality. The other half is its opposite, which is the "ought not world". Somehow Hume's guillotine left this part untouched.So the more complete map to describe those worlds would consist of a city part on the left side representing "ought not world" or something that conscious agents want to avoid, middle part of the city representing objective reality, city part on the right side representing "ought world", or something that is preferred by conscious agents. Those city parts are separated by two rivers, which represent natural separations between subjective and objective realities.
Argumentations over ought and ought not worlds are always done from surviving conscious agents' point of view. Failure to get the correct conclusion means waiting for extinction.