2018/12/31

Without junk-DNA evolution will become a destructive process

Modern Science has discovered that 100% of our genome is useful and meaningful. The junk-DNA theory is dead.

Here's some examples of thoughts that tell us a lot about what evolution believers think about junk-DNA and mutational load.

https://blogs.scientificamerican.com/the-curious-wavefunction/three-reasons-to-like-junk-dna/

Excerpt: "The third reason for accepting the reality of junk DNA is to simply think about mutational load. Our genomes, as of other organisms, have undergone lots of mutations during evolution. What would be the consequences if 90% of our genome were really functional and had undergone mutations? How would we have survived and flourished with such a high mutation rate? On the other hand, it's much simpler to understand our survival if we assume that most mutations that happen in our genome happen in junk DNA."


https://bigthink.com/paul-ratner/75-of-the-human-genome-is-junk-dna-claims-new-research

Excerpt: "Dan Graur, professor of biology and biochemistry, calculated that about 10 to 15 percent of the genome is actually functional, with the upper limit of 25 percent.
 
His reasoning stems from looking at how mutations affect a population’s DNA. Graur’s mathematical model allowed him to calculate the “mutational load” - the total genetic load of a population that results from the accumulation of bad or deleterious mutations. At some point the load can become too much and the population would go extinct."


Excerpt: "The estimated mutation rate in protein-coding genes suggested that only up to ∼20% of the nucleotides in the human genome can be selectively maintained, as the mutational burden would be otherwise too large."


https://sandwalk.blogspot.com/2009/11/genetic-load-neutral-theory-and-junk.html

Excerpt: "Because a large percentage of gene mutations are neutral, and because most of our genome is junk, we can easily tolerate 130 mutations per individual per generation without going extinct."


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014423/

Excerpt: "Currently, the rate of mutation in humans is estimated to be anywhere from 70–150 mutations per generation. By this line of reasoning, we would estimate that, at most, only 1% of the nucleotides in the genome are essential for viability in a strict sequence-specific way. However, more recent computational models have demonstrated that genomes could sustain multiple slightly deleterious mutations per generation. Using statistical methods, it has been estimated that humans sustain 2.1–10 deleterious mutations per generation. These data would suggest that at most 10% of the human genome exhibits detectable organism-level function and conversely that at least 90% of the genome consists of junk DNA."


https://geneticliteracyproject.org/2018/03/09/are-humans-genetically-loaded-for-extinction/

Excerpt: "We’ve also more than tripled in size as a group during that time. And all these issues are important in determining if, on an evolutionary scale, we’re in deep doo-doo.

Minnesota biologist PZ Myers doesn’t think it’s so bad. He points out that the number of genes an organism has is also important for determining genetic load. Which makes sense: several hundred mutations in a genome of 100,000 are far less than the same number in a genome of 20,000. And, according to his calculations, our genome (of about 20,000) is at the upper end of genes we can possibly carry with us. “We can’t have significantly more, or the likelihood of genes breaking down with our current mutation rate would mean that most of our children would be born dead of lethal genetic errors, or the burden of a swarm of small deficits to their fitness,” he wrote."

So, what does modern science say about useless DNA?

https://www.researchgate.net/publication/269187480_Non-coding_RNAs_Biological_functions_and_applications?fbclid=IwAR2RYi1Zw99F_-87r8sj0Q3z1FqHJQ19dCBHZUwDbSx2jaV4GPsBLO4ThRY

Excerpt: "Analyses of the international human genome sequencing results in 2004 converged to a consensual number of ~20 000 protein-coding genes, spanning over <2% of the total genomic sequence. Therefore, the developmental and physiological complexity of human beings remains unaccounted if viewed only in terms of the number of protein-coding genes; the epigenetic influences involving chromatin remodelling and RNA interference and alternative precursor messenger RNA splicing of functional protein-coding transcripts as well as post-translational modifications of proteins increase the diversity and the functionality of the proteome and likely explain the increased complexity. In addition, there has been an explosion of research addressing possible functional roles for the other 98% of the human genome that does not encode proteins. In fact, >90% of the human genome is likely to be transcribed yielding a complex network of overlapping transcripts that include tens of thousands of long RNAs with little or no protein forming capacity; they are collectively called non-coding RNA. This review highlights the fundamental concepts of biological roles of non-coding RNA and their importance in regulation of cellular physiology under disease conditions like cancer."

My comment: So, it's obvious that without a living junk-DNA theory, evolution will become a destructive process. And this is exactly what we are observing to occur in the wild and in the human genome. Evolution has never happened. Any change in organisms has been due to epigenetic regulation of pre-existing biological information OR corruption of information.

2018/12/30

Collapse of the Junk-DNA theory will destroy the theory of evolution

Without genomic junk, mutational load will drive species into extinction

As we already know, there are only about 19'000 DNA sequences used for protein encoding in the human genome.  It is less than in one of the smallest multicellular organisms, C. Elegans (length ~1 mm). According to the most recent studies, different proteins in our body are up to six million. Are there areas in the DNA that control how the cell reads the sequences used for protein encoding?

The ENCODE project in 2008-2102 systematically mapped the entire human genome in terms of transcription, transcription factors, chromatin structure, and histone modifications. The project discovered that 80.4% of our genome is biochemically active and functional especially outside of the protein coding sequences.
 

Despite functionality for such a large share of DNA was found, leading evolutionary biologists did not agree to believe that this part would be beneficial. For example, PZ Myers in several of his writings belittles the results of the ENCODE project.

Later research has discovered how cells use the non-coding region for many different purposes:

1. Dr. John Stamatoyannopoulos from the University of Washington states that Encode revealed 40 million different switches (epigenetic switches) in our genome that control and regulate these genes (protein coding sequences). According to the researchers, the area found by ENCODE is a kind of operating system. It is therefore clearly both useful and functional, and in no case any junk or useless filling.

2. The ENCODE project didn't discover how the cell uses the so-called STRs (Short Tandem Repeat) sections. These are short repeating DNA sequences that appear more like typing errors or noise. However, researchers have found that STR sequences are very important regulatory elements in our genome and affect about 10-15% of human phenotypical differences (their methylation levels).

3. Transposable elements (LINEs, SINEs, ERVs and DNA transposons) have all been found to be very important and useful. They have several different tasks. By reading them, cells typically construct non-coding RNA molecules, such as lncRNA, microRNA, siRNA, and PiRNA molecules.

4. Heterochromatin is tightly packed DNA in the chromosome. It has only recently been discovered that cellular mechanisms recruit 'ambulances', i.e. two-legged myosin engine proteins, to transport damaged DNA sequences in heterochromatin to be repaired at the nuclear pore complex. So the cell is also trying to fix faulty DNA.

Conclusion: The cell is capable of modifying DNA in many ways, either by combining sequences or by repairing already damaged strands. DNA is a passive data resource for the cell that it uses to build functional RNA molecules. Due to the passive role of DNA, there is no unnecessary or filling DNA in the cell, but everything is useful. It is a data warehouse, a pool from which the cell searches for appropriate sequences for different purposes using highly sophisticated guiding and control mechanisms.

The mutation load is so high that the cell is not able to correct all the errors. Disruptions in the epigenetic mechanisms and impaired performance result in the cell being unable to re-organize the damaged DNA at the ends of the chromosomes in the telomeres. This is why chromosomes are combined and their total count decreases.

In our own lifetime, it’s estimated that 40,000 species become extinct every year.

2018/12/26

Game changing study gives new meaning for Junk-DNA

Cells send damaged ‘junk DNA’ to the emergency room for repair

https://dornsife.usc.edu/news/stories/2830/cells-send-damaged-junk-dna-to-the-emergency-room-for-repair/

Excerpt: "The cell has its own paramedic team and emergency room to aid and repair damaged DNA, a new USC Dornsife study reveals.

The findings are timely, as scientists are delving into the potential of genome editing with the DNA-cutting enzyme CRISPR-Cas9 to treat diseases or to advance scientific knowledge about humans, plants, animals and other organisms, said Irene Chiolo, Gabilan Assistant Professor of Biological Sciences.

Genome editing has arrived before scientists have thoroughly studied the significance and impact of DNA damage and repair on aging and disease, such as cancer. Chiolo’s work has been revealing more about those processes.

For the study published today in Nature, Chiolo and her team used fluorescent markers to track what happened when DNA was damaged in fruit fly cells and mouse cells. They saw how the cells launch an emergency response to repair broken DNA strands from a type of tightly-packed DNA called heterochromatin.

“Heterochromatin is also referred to as the ‘dark matter of the genome’ because so little is known about it,” said Chiolo. “But DNA damage in heterochromatin is likely a major driving force for cancer formation.”

Don’t call it junk


Repeated DNA sequences have had a bad nickname, “junk DNA,” for about 20 years. Scientists decoding the genome called it junk because they were initially focused on understanding the functions of individual genes.

Since then, studies have shown that repeated DNA sequences are in fact essential for many nuclear activities, but their defective repair is also linked to aging and disease.

“Heterochromatin is mostly composed of repeated DNA sequences,” Chiolo said. “The low gene content is part of the reason why these sequences are less characterized.”

In fact, mutations that compromise heterochromatin repair result in massive chromosome rearrangements affecting the entire genome.

First responders take a walk

The scientists found that after the DNA strands are broken, the cell prompts a series of threads — nuclear actin filaments — to assemble and create a temporary highway to the edge of the nucleus. Then come the paramedics — proteins known as myosins.

“Myosins are conveyed as a walking molecule because they have two legs,” Chiolo said. “One [leg] is attached and the other moves. It’s like a molecular machine that walks along the filaments.”
 

Come on boy, let's fix you!
The myosins pick up the injured DNA, walk along the filament road and then reach the emergency room, a pore at the boundary of the nucleus.
“We knew, based on our prior study, that there was an emergency room — the nuclear pore where the cell fixes its broken DNA strands. Now, we have discovered how the damaged DNA travels there,” Chiolo said. “What we think is happening here is that the damage triggers a defense mechanism that quickly builds the road, the actin filament, while also turning on an ambulance, the myosin.” "

My comment: What an incredible mechanism! There is no junk-DNA in the genome because DNA is just passive form of information and the cell has several sophisticated mechanisms for modifying and reorganizing the DNA. This study also confirms my previous claims that heterochromatin contains a lot of faulty DNA. That's why it's packaged into tight caps in the ends of chromosomes. These are called telomeres.

These findings point to an incredibly sophisticated and super intelligent mechanism and they tell us about designed and created cellular systems.

2018/12/25

How a broken gene accelerates genetic degradation

Human genome is rapidly degrading due to genetic errors - MTHFR gene mutation is a critical defect

https://mthfrgenesupport.com/2018/07/mthfr-gene-mutation-defined-for-your-health-what-is-mthfr/

Excerpt: "An MTHFR gene mutation can replace one amino acid for another within the MTHFR enzyme, leading to a change in function. The MTHFR gene mutation alters the chain of amino acids that make up the MTHFR enzyme changing its overall shape. It’s important to understand that an enzyme’s shape gives rise to its function. So for example, the MTHFR C677T means that at place 677 on chromosome 1, the Cytosine has been changed to a Thymine. This change causes the amino acid sequence to change that makes the MTHFR enzyme.The result is a dysfunctional enzyme (it’s slower) and less 5-methylfolate production.
 
Methylation cycle is a very complex biochemical pathway.

The overall shape of the MTHFR enzyme varies based on what MTHFR gene mutations are present. Each unique mutation has a different impact on how the MTHFR enzyme performs within the body. There are currently 34 different known MTHFR gene mutations. The two most researched mutations are C667T and A1298C, which are the mutations we focus on most.

Is There One Type Of MTHFR Gene Mutation?

Depending on the mutation you have the consequences are slightly different. Each mutation follows a similar trend towards less methylation within the body or less active folate production (5-MTHF). If a mutation is present, the enzyme can have a 20% to 70% loss of function.

Since everyone has two copies of each gene (one from each parent), loss of function depends on whether there are one or two copies of the MTHFR gene mutation present.

One copy of a gene = Heterozygous (C677T= ~40% loss, A1298C=~20% loss) (This means you have one copy from mom OR dad)

Two copies of a gene = Homozygous (C677T=~70% loss, A1298C=~40% loss) (This means you have one copy from both your mom AND dad)

One copy of both C667T and A129C = compound heterozygous = ~50% loss

(This means mom and dad each gave you one copy of C667T or A1298C)

In general, less methylation occurs in people who have two copies of an MTHFR gene mutation.

MTHFR Mutations = Less Methylation

Methylation is responsible for turning multiple processes within cells “on or off”.

Proper methylation (adding/removing methyl groups (CH3) from molecules) within the body ensures cells are doing their jobs.

Think of methylation as a master switch. Any biochemical product that ends in MT is a methyltransferase. Methyls act as a switch for methyltransferases, they make them stop and go. Methyltransferases have important biochemical roles in our bodies. For example:
The breaking down of toxic oestrogens through hormone production via COMT
The health of cellular membranes and energy through choline production via PEMT
For a more indepth understanding of the importance of methyltransferases click here (your methyltransferase article))

When methylation is not working or down regulated, the body is not able to produce correct responses to the environment, damaging the body. Certain process within cells will be turned on or off for too long, leading to an impaired ability to:

  • Get rid of toxins (detoxification)
  • Repair and rebuild DNA/RNA
  • Produce and process hormones
  • Build immune cells
  • Repair cell membranes
  • Turn the stress response on and off
  • Metabolize fat
  • Produce energy
  • Recycle and build neurotransmitters
When these vital cellular processes are not working correctly, adverse symptoms can arise such as: cardiovascular disease, impaired immunity, chronic inflammation, diabetes, anxiety, depression, chronic fatigue, cancer, fibromyalgia infertility and miscarriages. Problems with methylation will amplify the symptoms of existing autoimmune and psychiatric conditions. For a more in depth analysis about the symptoms of MTHFR mutations click here.
(mthfr symptoms / conditions article)

It is important to know if you have a mutation in the MTHFR gene. Approximately 50-65% of the population has an MTHFR gene mutation."


My comment: MTHFR mutation is a serious example of genetic degradation. This common genetic error accelerates genetic degradation because it affects the methylation cycle. It typically results in hypomethylation. Methylation stabilizes the genome and RNA molecules. Hypomethylation is strongly associated with aberrant methylation profiles that lead to problems with cellular differentiation programs, gene expression and DNA transcription. It's obvious that MTHFR mutations increase the risk for having more mutations. Some of them end up in germ line.

People living with MTHFR genetic defect need to take care of proper nutrition and healthy life style. In this way they can mimimize the risks the mutation causes.

There are 561'119 gene-disease-associations in human genome at population level but the number of random beneficial DNA mutations is close to zero. Evolution is not happening.

2018/12/15

Efforts to create artificial life show the impossibility of abiogenesis

Top scientists are not able to create artificial life from scratch - Living organisms needed as models

https://www.nature.com/articles/d41586-018-07289-x

Excerpt: "There were just eight ingredients: two proteins, three buffering agents, two types of fat molecule and some chemical energy. But that was enough to create a flotilla of bouncing, pulsating blobs — rudimentary cell-like structures with some of the machinery necessary to divide on their own.

To biophysicist Petra Schwille, the dancing creations in her lab represent an important step towards building a synthetic cell from the bottom up, something she has been working towards for the past ten years, most recently at the Max Planck Institute of Biochemistry in Martinsried, Germany.

“I have always been fascinated by this question, ‘What distinguishes life from non-living matter?’” she says. The challenge, according to Schwille, is to determine which components are needed to make a living system. In her perfect synthetic cell, she’d know every single factor that makes it tick.

Researchers have been trying to create artificial cells for more than 20 years — piecing together biomolecules in just the right context to approximate different aspects of life. Although there are many such aspects, they generally fall into three categories: compartmentalization, or the separation of biomolecules in space; metabolism, the biochemistry that sustains life; and informational control, the storage and management of cellular instructions.

The pace of work has been accelerating, thanks in part to recent advances in microfluidic technologies, which allow scientists to coordinate the movements of minuscule cellular components. Research groups have already determined ways of sculpting cell-like blobs into desired shapes; of creating rudimentary versions of cellular metabolism; and of transplanting hand-crafted genomes into living cells. But bringing all these elements together remains a challenge.
“It’s much easier to take things apart than put them back together.” Dan Fletcher tells us about the challenges of building a synthetic cell.


The field is, nevertheless, imbued with a new sense of optimism about the quest. In September 2017, researchers from 17 laboratories in the Netherlands formed the group Building a Synthetic Cell (BaSyC), which aims to construct a “cell-like, growing and dividing system” within ten years, according to biophysicist Marileen Dogterom, who directs BaSyC and a laboratory at Delft University of Technology. The project is powered by an €18.8-million (US$21.3-million) Dutch Gravitation grant.

In September, the US National Science Foundation (NSF) announced its first programme on synthetic cells, funded to the tune of $10 million. And several European investigators, including Schwille, have proposed building a synthetic cell as one of the European Commission’s Future and Emerging Technologies Flagship schemes, which receive funding of €1 billion.

Bottom-up synthetic biologists predict that the first fully artificial cells could spark to life in little more than a decade. “I’m pretty sure we’ll get there,” says Schwille.

All in the packaging

Research groups have made big strides recreating several aspects of cell-like life, especially in mimicking the membranes that surround cells and compartmentalize internal components. That’s because organizing molecules is key to getting them to work together at the right time and place. Although you can open up a billion bacteria and pour the contents into a test tube, for example, the biological processes would not continue for long. Some components need to be kept apart, and others brought together.
“To me, it’s about the sociology of molecules,” says Cees Dekker, a biophysicist also at Delft University of Technology.

For the most part, this means organizing biomolecules on or within lipid membranes. Schwille and her team are expert membrane-wranglers. Starting about a decade ago, the team started adding Min proteins, which direct a bacterial cell’s division machinery, to sheets of artificial membrane made of lipids. The Mins, the researchers found, would pop on and off the membranes and make them wave and swirl. But when they added the Mins to 3D spheres of lipids, the structures burst like soap bubbles, says Schwille. Her group and others have overcome this problem using microfluidic techniques to construct cell-sized membrane containers, or liposomes, that can tolerate multiple insertions of proteins — either into the membranes themselves or into the interior.
 
Schwille’s graduate student, Thomas Litschel, and his collaborators dissolved the Min proteins in water and released droplets of the mixture into a rapidly spinning test tube. Centrifugal force pulls the droplets through layers of dense lipids that encapsulate them along the way. They come out at the other end as liposomes measuring 10–20 micrometres across — about the size of an average plant or animal cell. These liposomes, known as giant unilamellar vesicles (GUVs), can be made in different ways, but in Litschel’s hands, the Min proteins caused the GUVs to pulsate, dance around and contract in the middle.

Schwille’s group wants to capitalize on its knowledge of these proteins, which can produce membrane patterns and self-organize. “We understand these molecules really well,” she says. “We’d like to see how far we can get with relatively simple elements like the Mins.” Perhaps, as Litschel’s work hints, the team could use the proteins to mould membranes for division or to gather components at one end of a synthetic cell. Just as some physicists might use duct tape and tinfoil to fine-tune their experiments, Schwille says she hopes that these handy biological molecules will give her the ability to tinker with cell-like structures: “I’m an experimentalist to the bone.”

Dekker’s team members have also filled liposomes with their favourite proteins using a microfluidic chip (see ‘The bubble machines’). On the chip, two channels containing lipid molecules converge on a water-filled channel and spit out cell-sized liposomes that can hold various biological molecules, either stuck through the membrane or free-floating inside the container.

His group has experimented with pressurizing, deforming and reshaping the liposomes to take on non-spherical shapes that mimic cells better. Microfluidic devices give researchers more control to move, sort and manipulate liposomes using micro-channels that operate almost like circuits. This year, the Dekker lab designed a chip that could mechanically split a liposome in two by pushing it up against a sharp point.

“This, of course, is not what we are after — we want to demonstrate division from the inside, but it still tells us interesting information,” says Dekker. Examples include the force it takes to divide a cell, and what types of physical manipulation the liposomes can tolerate. Along the same lines, his team has also played around with the shape of living Escherichia coli cells — making them wider or square by growing them in nanofabricated silicone chambers. In this way, team members can see how cell shape affects the division machinery, and assess how the Min proteins work in cells of different size and shape.

“We play with nanofabrication techniques and do things a normal cell biologist would never do,” he says. “But a strange biophysicist like me can do this.”

Adding energy to the system

Now that it’s possible to add components to the liposome bubbles without popping them, groups can plan how to make molecules work together. Almost anything life-like requires cellular energy, usually in the form of ATP. And although this can be added from the outside to feed a synthetic system, many biologists working on bottom-up approaches argue that a true synthetic cell should have its own power plant, something similar to an animal cell’s mitochondrion or a plant’s chloroplast, both of which make ATP.

Joachim Spatz’s group at the Max Planck Institute for Medical Research in Heidelberg, Germany, has built a rudimentary mitochondrion that can create ATP inside a vesicle.

To do this, his team took advantage of new microfluidic techniques. First, they stabilized GUVs by placing them inside water-in-oil droplets surrounded by a viscous shell of polymers. Then, as these droplet-stabilized GUVs flowed down a microchannel, the team injected big proteins into them, either inside the vesicle or embedded in the membrane’s surface (see ‘The assembly lines’).

They loaded these membranes with an enzyme called ATP synthase, which acts as a kind of molecular waterwheel, creating ATP energy from precursor molecules as protons flow through the membrane. By adding acid to boost protons outside the GUVs, the team drove ATP’s production on the inside.

ATP synthase - an energy-creating rotary motor
engine  in a living cell.
Spatz explains that researchers could cycle the GUVs around the microchannel again for another protein injection, to sequentially add components. For instance, the next step could be to add a component that will automatically set up the proton gradient for the system.

“That’s an important module, like you have in real life,” says Spatz.

Another Max Planck synthetic-biology group led by biochemist Tobias Erb has been chipping away at other approaches to constructing cellular metabolic pathways. He’s particularly interested in pathways that allow photosynthetic microbes to pull carbon dioxide from the environment and make sugars and other cellular building blocks.

Erb, a group leader at the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany, takes a blank-slate approach to synthesizing cellular metabolic pathways. “From an engineering point of view, we think about how to design,” he says, “and then we build it in the lab”.

His group sketched out a system design that could convert CO2 into malate, a key metabolite produced during photosynthesis. The team predicted that the pathway would be even more efficient than photosynthesis. Next, Erb and his team searched databases for enzymes that might perform each of the reactions. For a few, they needed to tweak existing enzymes into designer ones.

In the end, they found 17 enzymes from 9 different organisms, including E. coli, an archaeon, the plant Arabidopsis and humans. The reaction, perhaps unsurprisingly, was inefficient and slow.

“We put a team of enzymes together that did not play well together,” says Erb. After some further enzyme engineering, however, the team has a “version 5.4” that Erb says operates 20% more efficiently than photosynthesis.

Expanding this work, Erb’s group has begun constructing a crude version of a synthetic chloroplast. By grinding up spinach in a blender, and adding its photosynthesis machinery to their enzyme system in the test tube, the biologists can drive the production of ATP and the conversion of CO2 to malate — solely by shining ultraviolet light on it.

Although everything can work for a brief time in a test tube, says Erb, “at the end, we would like it compartmentalized, like a chloroplast”. He’s excited to collaborate with synthetic biologists such as Kate Adamala, who can build and control complex compartments.

Adamala’s group at the University of Minnesota in Minneapolis is working on ways to build programmable bioreactors, by introducing simple genetic circuits into liposomes and fusing them together to create more-complex bioreactors. She calls them “soap bubbles that make proteins”.

Her group builds these bioreactors using a spinning tube system similar to Schwille’s, but which produces smaller liposomes. The researchers add circles of DNA called plasmids that they have designed to perform a particular function, along with all the machinery needed to make proteins from DNA.

For instance, her group has made liposome bioreactors that can sense an antibiotic in their environment through membrane pores and can generate a bioluminescent signal in response.

By fusing simple bioreactors together sequentially, the team can construct more-complex genetic circuits. But the systems start to break down as they expand to include ten or so components. This is a major challenge for the field, Adamala says. In a real cell, proteins that might interfere with each other’s actions are kept apart by a variety of mechanisms. For much simpler synthetic cells, biologists must find other ways to impose that control. This could be through external gatekeeping, in which the experimenter decides which liposomes get mixed together and when. It might also be accomplished through chemical tags that regulate which liposomes can fuse together, or through a time-release system.

Informational injections

Another key to making a cell is getting the software right. Enabling a synthetic cell to follow scientists’ instructions and to replicate itself will require some way of storing and retrieving information. For living systems, this is done by genes — from hundreds for some microbes, to tens of thousands for humans.

How many genes a synthetic cell will need to run itself is a matter of healthy debate. Schwille and others would like to keep it in the neighbourhood of a few dozen. Others, such as Adamala, think that synthetic cells need 200–300 genes.

Some have chosen to start with something living. Synthetic biologist John Glass and his colleagues at the J. Craig Venter Institute (JCVI) in La Jolla, California, took one of the smallest-known microbial genomes on the planet, that of the bacterium Mycoplasma mycoides, and systematically disrupted its genes to identify the essential ones. Once they had that information, they chemically stitched together a minimal genome in the laboratory.

This synthesized genome contained 473 genes — about half of what was in the original organism — and it was transplanted into a related bacterial species, Mycoplasma capricolum. In 2016, the team showed that this minimal synthetic genome could ‘boot up’ a free-living, although slow-growing organism. Glass thinks that it will be hard to decrease that number much more: take any gene away, and it either kills the cells or slows their growth to near zero, he says.

He and his JCVI colleagues are compiling a list of ‘cellular tasks’ based on the latest version of their creation, JCVI-syn3.0a, which could act as a blueprint of a cell’s minimal to-do list. But for about 100 of these genes, they can’t identify what they do that makes them essential.

As a next step, and supported by an NSF grant of nearly $1 million, Glass and Adamala will attempt to install the JCVI-syn3.0a genome into a synthetic liposome containing the machinery needed to convert DNA into protein, to see whether it can survive. In that case, both the software and the hardware of the cell would be synthetic from the start.

If it could grow and divide, that would be a tremendous step. But many argue that to truly represent a living system, it would also have to evolve and adapt to its environment. This is the goal with the most unpredictable results and also the biggest challenges, says Schwille. “A thing that just makes itself all the time is not life — although I would be happy with that!” she says. “For a cell to be living, it needs to develop new functionality.”

Glass’s team at the JCVI has been doing adaptive laboratory evolution experiments with JCVI-syn3.0a, selecting for organisms that grow faster in a nutrient-rich broth. So far, after about 400 divisions, he and his team have obtained cells that grow about 15% faster than the original organism. And they have seen a handful of gene-sequence changes popping up. But there’s no evidence yet of the microbe developing new cellular functions or increasing its fitness by leaps and bounds.

Erb says that working out how to add evolution to synthetic cells is the only way to make them interesting. That little bit of messiness in biological systems is what allows them to improve their performance. “As engineers, we can’t build a perfect synthetic cell. We have to build a self-correcting system that becomes better as it goes,” he says.

Synthetic cells could lead to insights about how life might look on other planets. And synthetic bioreactors under a researcher’s complete control might offer new solutions to treating cancer, tackling antibiotic resistance or cleaning up toxic sites. Releasing such an organism into the human body or the environment would be risky, but a top-down engineered organism with unknown and unpredictable behaviours might be even riskier.

Dogterom says that synthetic living cells also bring other philosophical and ethical questions: “Will this be a life? Will it be autonomous? Will we control it?” These conversations should take place between scientists and the public, she says. As for concerns that synthetic cells will run amok, Dogterom is less worried. “I’m convinced our first synthetic cell will be a lousy mimic of what already exists.” And as the engineers of synthetic life, she and her colleagues can easily incorporate controls or a kill switch that renders the cells harmless.

She and other synthetic biologists will keep pushing ahead exploring the frontiers of life. “The timing is right,” says Dogterom. “We have the genomes, the parts list. The minimal cell needs only a few hundred genes to have something that looks sort of alive. Hundreds of parts is a tremendous challenge, but it’s not thousands — that’s very exciting.”

My comment: Abiogenesis has been proved to be impossible with these efforts to create artificial life. Only those 'eight ingredients' are so complex elements that it makes it impossible for life to just pop out somewhere by random chance. For example, the  probability to get a working protein using 20 amino acids is about 1:10^202. The number of atoms in the whole universe is about 10^87.

And the most serious problem: There is no 'trial and error' -mechanism in the non-living nature.

Abiogenesis is a nightmare for evolution believers, that's why they want to keep it separate from their theories. But the origin of life is still a mystery for them. Life arises only from LIFE. The theory of evolution is a belief system. There is no mechanism for evolution and there are no scientific evidence for evolution. Don't be deceived.

2018/12/07

A typical example of genetic degradation - Galapagos Giant Tortoises

The giant tortoises of Galapagos are endangered due to rapid loss of genetic diversity

https://www.researchgate.net/publication/8602585_Genetic_analysis_of_a_successful_repatriation_programme_Giant_Galpagos_tortoises

Excerpt: "As natural populations of endangered species dwindle to precarious levels, remaining members are sometimes brought into captivity, allowed to breed and their offspring returned to the natural habitat. One goal of such repatriation programmes is to retain as much of the genetic variation of the species as possible. A taxon of giant Galápagos tortoises on the island of Española has been the subject of a captive breeding-repatriation programme for 33 years. Core breeders, consisting of 12 females and three males, have produced more than 1200 offspring that have been released on Española where in situ reproduction has recently been observed. Using microsatellite DNA markers, we have determined the maternity and paternity of 132 repatriated offspring. Contributions of the breeders are highly skewed. This has led to a further loss of genetic variation that is detrimental to the long-term survival of the population. Modifications to the breeding programme could alleviate this problem."
 
My comment: These Darwin's favourite pets show us what is happening in the wild. Organisms are experiencing rapid loss of genetic diversity. Scientists know that the only way to rescue them is to breed them with their predecessors. This has to be done in captivity, because pheromones control mating behaviour and different species of tortoises will not mate in the wild. Genetic diversity can be rejuvenated only by using biological information existing in the same kind. But the total amount of biological information is still only decreasing in the species groups. And this same phenomenon can be observed all over nature. There is no mechanism for evolution. Don't be deceived.

2018/12/05

No random beneficial mutations but a huge number of genetic maladies - Genetic entropy

15,000 human genetic illnesses due to over half a million harmful mutations in human genome

https://www.scientificamerican.com/article/new-gene-editing-pencil-erases-disease-causing-errors/

Excerpt: "There are more than 50,000 known human genetic maladies that have, in most cases, few good treatments and no cure. Now researchers at the Broad Institute of Harvard and MIT have developed a new tool that would theoretically make it possible to correct the genetic errors behind about 15,000 of these illnesses—including sickle-cell disease, cystic fibrosis and several forms of congenital deafness and blindness.

Standard gene-editing tools, such as the well-known CRISPR–Cas9 system, function like scissors; they can cut an offending gene from a strand of DNA. This could be useful against diseases such as Huntington’s, which is caused by duplications of genetic material.

The new tool, called ABE (adenine base editors), is more like an editing pencil, according to lead researcher David Liu. It lets scientists precisely change individual pairs of bases—the “letters” that form the “sentences” of the vast human genome—and thus might help address diseases like sickle cell that can be treated with a single letter change. Liu emphasizes that one tool is not better than the other; rather they can be used to address different types of problems.

But before ABE can be tried in human patients, Liu says, doctors would need to determine when to intervene in the course of a genetic disease. They would also have to figure out how to best deliver the gene editor to the relevant cells—and to prove the approach is safe and effective enough to make a difference for the patient.

Genes are made up of DNA—two long, parallel strands of molecules called nucleotides that are linked by pairs of chemical bases. The base A (adenine) always pairs with T (thymine); and G (guanine) joins with C (cytosine). But when the genetic machinery makes mistakes and puts a pair in the wrong place, it sometimes leads to disease. The new tool targets genetic errors in which an A–T base pair should be a G–C.
 
Liu is a professor of chemistry at Harvard University and a vice chair of the faculty at the Broad Institute. Along with his students and postdoctoral researchers he had previously developed base editors that convert C–G base pairs into T–A pairs. (The order is important, so a G–C mistake is not the same as a C–G one.) Liu, who is also an investigator with the Howard Hughes Medical Institute, said Tuesday in a news conference that he and others have been working on additional tools, which could correct other types of “spelling mistakes” in DNA. This led them to ABE.

The new ABE technique uses an enzyme Liu and his colleagues developed. It rearranges the atoms in A so they form a base that resembles G in a DNA strand. The ABE system also nicks the mated DNA strand that contains the T. The cell’s repair mechanisms then turn on to fix the tear. In doing so, the cell replaces the T with a C, correcting the other half of the base pair. The net result is the troublesome A–T base pair is converted into a beneficial G–C pair.

Using ABE in a lab dish, Liu and his colleagues were able to precisely edit genes that cause a hereditary form of hemochromatosis—a disease that leads the body to store too much iron, causing pain, fatigue, weakness and, if untreated, liver and heart failure. They also used ABE to install a different genetic mutation that compensates for the DNA defect that causes sickle-cell disease.

The ABE gene-editing process is efficient, effectively editing the relevant spot in the genome an average of 53 percent of the time across 17 tested sites, Liu said. It caused undesired effects less than 0.1 percent of the time, he added. That success rate is comparable with what CRISPR can do when it is cutting genes.

Dirk Hockemeyer, an assistant professor at the University of California, Berkeley, who was not involved in the Broad research, said he is impressed in the work and the tool the team developed. But it is still a long way from helping patients. “In clinical applications the key question is always delivery, delivery, delivery: How do I get the editing agent to the position in the cell that I want to repair?” he says. But “if it cures a single disease, we should all be happy.”"

My comment: I just wrote an article about random beneficial mutations in human genome. Seems that they don't exist. You can read more about it here. However, there are over half a million harmful genetic mutations that have resulted in 15,000 genetic diseases. Human genome is rapidly degrading. Mutation rate is fast: 100-200 new germline mutations will be brought by every generation. This study revealed 1 million human genome sequence errors. However, genetically (DNA) all people are 99.9 % similar. The 0.1% difference is strongly related to hereditary diseases. Behind this scientific fact is the NHGRI (The National Human Genome Research Institute). Scientists try to repair 32,000 GC > AT mutations in human genome because any imaginary selection is not able to weed them out.

Evolution has no mechanism because there are no random beneficial mutations and genomes are degrading so rapidly. Don't get lost.

2018/12/04

Random beneficial DNA mutations? Forget them.

This article debunks the false claims about random beneficial mutations and evolution

Evolution believers claim that random mutations and selection lead to slow evolution. Random mutations are assumed to happen in DNA. Evolution believers often address us 5-10 examples of random beneficial mutations. Let's investigate those claims.

1. Lactose tolerance

This is the most popular argument used by evolution believers. They claim that a single SNP (single nucleotide polymorphism), a point mutation results in lactose persistence. This is a pseudoscientific claim. Modern science has discovered that lactose tolerance is regulated by epigenetic mechanisms, such as methylation levels of MCM6 and LCT genes. You can read more about this fascinating mechanism from here:

https://sciencerefutesevolution.blogspot.com/2018/09/lactose-tolerance-is-regulated-by.html

Excerpt: "Most importantly, however, cross-validation analysis revealed that methylation at the LCT promoter and enhancer was highly predictive of lactase enzymatic activity, and the persistence/non-persistence phenotype. The predictive power outperformed the hitherto existing genotype at rs4988235, which fails prediction for the C/T genotype."

2. High altitude adaptation of Tibetans

This is a common claim that one point mutation leads to a better adaptation to high altitudes within Tibetan people. But again modern science has revealed that epigenetic mechanisms are also behind this clever adaptation:

https://www.researchgate.net/publication/320378665_Epigenetic_signatures_of_high_altitude_adaptation_in_Tibetan_population

Excerpt: "Analysis of WGBS data was performed using various statistical/bioinformatics tools such as bedtools, Bioconductor and R package to find out methylation sites that are significantly different. We observed 6 differentially methylated regions in Tibetans, highland population, of which, 5 were hypo methylated and one was hypermethylated. The present study reveals differential hypo methylation of CYP2E1 and CRELD1 genes, previously reported to be involved in high altitude adaptation (Simonson et al., 2010; Dong et al., 2014), which would of greater interest. Besides this, we observed novel epigenetic differences in chromosome 7, 11 and 15."
 

3. Adaptations to diving in the Bajau

One of the newest claims about random beneficial mutations is the adaptation to diving in the Bajau people. Evolution believers again claim that one point mutation (PDE10A) causes a larger spleen which results in more efficient production of red blood cells. There is at least one pseudoscientific research made over this:

https://pag.confex.com/pag/xxvi/recordingredirect.cgi/oid/Recording3080/paper27788_1.pdf


That study didn't take into account epigenetic mechanisms, such as DNA methylation profiles, histone epigenetic markers or non coding RNA molecules. That study has found only one point mutation and based on that, it claims that adaptation to diving is caused by a genetic mutation. But as that synopsis summarizes, it's PROBABLY a genetic effect. Serious scientists already know that exercise will not change the sequence of the DNA. Methylation levels can be altered and this can result in DNA errors or markers. But the DNA sequence error is not the reason for a larger spleen or increased levels of T4 hormone.
https://www.researchgate.net/post/does_genetic_change_with_the_exercise

Excerpt: "No doubt that the genecis code (A,G,C,T) will not change in response to any intra- or extracellular stimuli (e.g., exercise). However, exercise might trigger epigenetic changes (DNA methylation, histone modifications, ncRNAs), which will modulate the accessibility to the genetic code. If such epigenetics changes are inheritable, then there is a possibility of ecxercise-mediated epigenetic changes that might result in the selection of fitter individuals. In the literatüre, there are examples of permanent changes in the epigenetic code that can be inherited."

Another possibility to consider is a potential for epitranscriptomics changes in the germ cells. If excersice might induce such inheritable changes, I can forsee a possibility for exercise-mediated epitranscriptomics changes in the germ cells that might change the fate of the fertilezed egg :)"



4. Apolipoprotein AI-Milano


Apo-AI is one of the High Density Lipoproteins, already known to be beneficial because they remove cholesterol from artery walls.


The variation of this gene is based on alternative splicing. It means the gene itself doesn't get changed but the transcript may be altered due to nutrient adaptive reasons by a very clever RNA-mediated mechanism.

5. Increased bone density

“Current research data suggest epigenetic modifications (DNA methylation and histone acetylation) and microRNAs (miRNAs) are responsive to acute aerobic and resistance exercise in brain, blood, skeletal and cardiac muscle.”


6. CCR5Δ32, the HIV-1 immunity protein

This is also based on alternative splicing. Most of the human protein production is based on the alternative splicing so the variation of this receptor is not a mutant, although many scientific articles say so.
http://www.jmolecularsignaling.com/articles/10.1186/1750-2187-7-13/

7. Sickle cell anemia

Scientists try to repair the broken gene causing this severe disease. 

https://medicalxpress.com/news/2018-12-sickle-cell-anemia-treatment-safely.html

Excerpt: "Because of the lack of detailed medical records, the best available estimates are that 50 to 90 percent of infants with SCA born in sub-Saharan Africa die before the age of 5, according to a 2017 paper published by Cincinnati Children's researchers that included Ware."


My comment: Epigenetic adaptation will not result in any kind of evolution because epigenetic mechanisms only regulate pre-existing biological information. Epigenetic modifications typically cause subtle DNA errors. That's why there are 561,119 harmful genetic defects in human genome at population level. The number of disease-causing germline mutations is also over 300,000. One in five 'healthy' adults may carry disease-related genetic mutations. Genetic entropy is a biological fact. The number of random beneficial mutations seems to be a ZERO. The theory of evolution is the most serious heresy of our time. Don't be deceived.

2018/12/02

Species are islands in sequence space. Intermediates disappear.

The biggest problems with Darwinian stories are emphasized as researchers discover the human race came forth from one couple

https://www.wnd.com/2018/11/animals-1st-appeared-alongside-1st-humans-expert-explains/

Excerpt: "A new scientific study that concludes the human race sprang from a single adult couple, as the Bible records, also aligns with the Bible’s account of animals appearing at the same time. WND reported over the weekend the sweeping survey of the genetic code by the Rockefeller University and the University of Basel, Switzerland.

“This conclusion is very surprising,” said David Thaler, a research associate from the University of Basel, who did the study with Mark Stoeckle. “And I fought against it as hard as I could.”

Nathaniel T. Jeanson, an expert in cell and developmental biology who works with Answers in Genesis, pointed out the research revealed “the vast majority of animal species arose contemporary with modern humans.”

Jeanson, who holds a Ph.D. from Harvard, contends the research, which focuses on mitochondrial DNA, conflicts with evolutionary theory, which posits animal forms preceded humans, because humans developed from animal forms.
 

In an online report, Jeanson explained that “DNA barcoding” is being used in the field of classification of life. In short, DNA barcoding uses a genetic marker in an organism’s DNA to identify it as belonging to a particular species

The new study, he said, found that “explaining the origin of the pattern of DNA barcodes would be in large part explaining the origin of species.

The researchers concluded there is “a single sequence” of genetics for humans.

“The simple hypothesis,” the researchers said, “is that the same explanation offered for the sequence variation found among modern humans applies equally to the modern populations of essentially all other animal species.”

“Namely that the extant population, no matter what its current size or similarity to fossils of any age, has expanded from mitochondrial uniformity within the past 200,000 years.”

Stoeckle and Thaler claim “the vast majority of species have originated contemporary with modern humans.”

Jeanson believes the Bible suggests a time span of 6,000 years, not 200,000.

“We now have two decades’ worth of direct measurements of the rate at which human mtDNA mutates, and it matches exactly the 6,000-year timescale and rejects the evolutionary timescale (see ‘Genetics Confirms the Recent, Supernatural Creation of Adam and Eve’ and references therein),” he wrote. “Thus, taking Stoeckle and Thaler’s results to their logical conclusion, we can revise their statement to ‘Modern human [mitochondrial DNA] originated from conditions that imposed a single sequence on these genetic elements’ about 6,000 years ago.”"

My comment: The position of evolution proponents is getting weak. Discoveries of modern science reveal the serious problems with a man-made story, Darwinian evolution. Scientists were surprised with the results of the mtDNA study. The following comments point out that they are struggling with their explanations:

“This conclusion is very surprising, and I fought against it as hard as I could,” Thaler told AFP.

Another intriguing insight from the study, says Mr. Ausubel, is that “ genetically, the world is not a blurry place. It is hard to find ‘intermediates’ - the evolutionary stepping stones between species. The intermediates disappear.”

Dr. Thaler notes: “Darwin struggled to understand the absence of intermediates and his questions remain fruitful.”

“The research is a new way to show that species are ‘islands in sequence space.’ Each species has its own narrow, very specific consensus sequence, just as our phone system has short, unique numeric codes to tell cities and countries apart.”

Adds Dr. Thaler: “ If individuals are stars, then species are galaxies. They are compact clusters in the vastness of empty sequence space.”


Variation of species is a very biblical phenomenon (after its kind). The clear absence of intermediates refutes the theory of evolution. Over 90% of animal species appeared about the same time as human beings. Species are islands in sequence space. What else do we need to have scientific support for Creation?