Genes Out of Thin Air, and Other Wonders

Human DNA comprises 98% non-coding DNA and only 2% coding DNA. But that is not the end of the story.

Noncoding DNA is defined as all of the DNA sequences within a genome that are not found within protein-coding exons, and so are never represented within the amino acid sequence of expressed proteins. By this definition, more than 98% of the human genomes is composed of ncDNA. __

But we will soon see that some “non-coding” DNA is magically transformed into coding DNA. And that can make a very big difference.

New Genes Emerge out of “Nowhere”

It looks as if humans — and other animals — are creating new genes out of “junk DNA.” These new genes are referred to as de novo genes, and may be one of the keys to “rapid evolution” of species and sub-species. To include these de novo genes in the above Venn diagram, you would need to create a new circle that originated inside the “junk DNA” circle, but then quickly moved outside the non-coding circles entirely, and into a circle labeled “coding DNA.”

Researchers are beginning to understand that de novo genes seem to make up a significant part of the genome, yet scientists have little idea of how many there are or what they do. What’s more, mutations in these genes can trigger catastrophic failures. “It seems like these novel genes are often the most important ones,” said Erich Bornberg-Bauer, a bioinformatician at the University of Münster in Germany.

… In 2006, Begun found some of the first evidence that genes could indeed pop into existence from noncoding DNA. He compared gene sequences from the standard laboratory fruit fly, Drosophila melanogaster, with other closely related fruit fly species. The different flies share the vast majority of their genomes. But Begun and collaborators found several genes that were present in only one or two species and not others, suggesting that these genes weren’t the progeny of existing ancestors. Begun proposed instead that random sequences of junk DNA in the fruit fly genome could mutate into functioning genes.

… Scientists have now catalogued a number of clear examples of de novo genes: A gene in yeast that determines whether it will reproduce sexually or asexually, a gene in flies and other two-winged insects that became essential for flight, and some genes found only in humans whose function remains tantalizingly unclear.

At the Society for Molecular Biology and Evolution conference last month, Albà and collaborators identified hundreds of putative de novo genes in humans and chimps — ten-fold more than previous studies — using powerful new techniques for analyzing RNA. Of the 600 human-specific genes that Albà’s team found, 80 percent are entirely new, having never been identified before.

Scientists also want to understand how de novo genes get incorporated into the complex network of reactions that drive the cell, a particularly puzzling problem. It’s as if a bicycle spontaneously grew a new part and rapidly incorporated it into its machinery, even though the bike was working fine without it. “The question is fascinating but completely unknown,” Begun said. ___ New Genes Magically Appear

These de novo genes tend to produce shorter protein sequences, more likely to be regulatory in nature than structural.

Will humans use these “de novo” genes to evolve into a new species with super-intelligence, super-strength, and much longer and healthier lifespans? It is a possibility, particularly if we can learn more about how gene networks and cell networks work together to determine lifespan and other cellular and tissue efficiencies.

… it’s not the the accumulation of damages that is responsible for aging, but rather the properties of the gene network itself. The good news is that even we are playing with a terrible hand at first, there is a chance we can still win by changing the features of our network and making it stable. For example, by optimizing misfolded protein response or DNA repair.

So what does this paper mean to all of us? It means that if we analyze transcriptome data theoretically would be able to understand how we can transform a normally aging organism into a negligibly aging one. ___ Hacking Gene Networks

Let’s take a look at the research paper that examines the gene networks that may make the difference between short lifespans and very long lifespans:

A growing number of animal species are recognized to exhibit what is called negligible senescence, i.e. they do not show measurable reductions with age in their reproductive ability or functional capacities1. Death rates in negligibly senescent animals do not increase with age as they do in senescent organisms [ed – such as humans].

In contrast, aging in most species studied leads to an exponential increase of mortality with age, commonly characterized by the Gompertz or Gompertz-Makeham laws12,13, which may be a direct consequence of underlying instability of key regulatory networks. Recent studies of gene expression levels in the naked mole rat and long-lived sea urchin14 showed that the number of their genes exhibiting expression changes with age is lower than in other animal species2,3,4,14,15,16. Therefore, the lifelong stability of the transcriptome may be a key determinant of longevity, and improving the maintenance of genome stability may be a sound strategy to defend against numerous age-related diseases…. We show that under a very generic set of assumptions there exist two distinctly different classes of aging dynamics, separated by a sharp transition depending on the genome size, regulatory-network connectivity, and the efficiency of repair systems. If the repair rates are sufficiently high or the connectivity of the gene network is sufficiently low, then the regulatory network is very stable and mortality is time-independent in a manner similar to that observed in negligibly senescent animals. Should the repair systems display inadequate efficiency, a dynamic instability emerges, with exponential accumulation of genome-regulation errors, functional declines and a rapid aging process accompanied by an exponential increase in mortality. The onset of instability depends on the gene-network properties only, irrespective of genotoxic stress levels, and as such can be viewed as being hard-wired in the genome of the species. The two regimes also show dramatically different dynamics of stress-resistance with age: stable genetic networks are more robust against noise, and the efficacy of stress defenses does not decline with age. In contrast, the ability of “normally aging” animals to cope with stresses deteriorates with age. Moreover, the lack of stability of the gene regulatory networks may prevent complete recovery of organisms experiencing strong stresses, as can be shown by careful investigation of life histories of animals, such as fruit flies, surviving traumatic damage early in life. __ Gene Network Stability Can Determine Stress Resistance and Aging

One of the secrets of longevity may well be the stability of gene networks. Finding feasible ways to increase gene network stability in humans — without causing other problems — is likely to prove difficult and time-consuming. It also seems promising, so it is worth looking into.

New tools for editing genes inside cells may offer the ability to cure diseases that were previously believed incurable — such as HIV.

In a study published by the Proceedings of the National Academy of Sciences, Dr Khalili and colleagues detail how they created molecular tools to delete the HIV-1 proviral DNA… When deployed, a combination of a DNA-snipping enzyme called a nuclease and a targeting strand of RNA called a guide RNA (gRNA) hunt down the viral genome and remove the HIV-1 DNA.

… From there, the cell’s gene repair machinery takes over, soldering the loose ends of the genome back together – resulting in virus-free cells.

Dr Khalili’s lab engineered a 20-nucleotide strand of gRNA to target the HIV-1 DNA and paired it with a DNA-sniping enzyme called Cas9 and used to edit the human genome.

‘We are working on a number of strategies so we can take the construct into preclinical studies,’ Dr Khalili said.

‘We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it.’ ____ Eliminating HIV From Every Cell Using Gene Snipping

It may work. Or, it may lead to other paths that will prove more doable. It is worth trying, just to become more proficient in the use of the gene editing tools.

Inhalable DNA particles for gene-therapy in lung tissue

Gene therapies capable of restoring youthful levels of GDF-11 and myostatin might be particularly useful in anti-aging regimens

Building arrays of thousands of custom organoids, using DNA-guided 3D printing Such arrays would comprise powerful research tools for developing much better and safer drugs and genetic therapies.

Cross Species Drag and Drop Gene Circuits: Powerful tool for synthetic biology

We are seeing the emergence of a brave new world of genetic science and technology. What was recently science fiction is now being worked out in laboratories (and garages) around the world. Try not to let the new developments bite you in the nethers.

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6 Responses to Genes Out of Thin Air, and Other Wonders

  1. bob sykes says:

    Biology, not physics, was the breakthrough science of the 20th Century, and it will continue to be the main source of scientific innovation in the 21st Century. God knows what marvels and horrors await.

    The phrase “junk DNA” is merely an indicator of our ignorance about what is going on in the genome. DNA is the most energetically expensive molecule to synthesize in the whole array of biomolecules. It is unreasonable that organisms should synthesize large amount of junk molecules, so the junk must actually have a use. Most of the regulatory parts of DNA were only recently discovered, Much more is about to be.

    One is reminded of the urban legend that we use only 10% of our brains. (The movie Lucy is based on this idiocy.) The brain, however, is the most energetically expensive organ in the body, consuming some 20% of our caloric intake. The fact is, we use all of our brains. Just like we use all of our DNA.

  2. Jim says:

    If we were using all of our DNA all the time then its evolution would be constrained by its existing functions. Some of the junk DNA is probably “scratch paper” on which evolution can doodle until either it comes up with something disastrous and is purged by natural selection or it comes up with something useful which then goes on to become standard.

    But it’s also true that probably a lot of the “junk DNA” does stuff that we don’t understand at present.

  3. infowarrior1 says:

    I am looking forward to the promises and with trepidation in regards to the risks.

  4. Matt Musson says:

    DNA is even more complex than we believed. Apparrently much more complex.

    Sorry Darwin. DNA is irreducibly complex.

  5. Pingback: Outside in - Involvements with reality » Blog Archive » Chaos Patch (#78)

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