Are genetic mutations random in humans?
Israeli study says no

A study by the University of Haifa researchers claims not all genetic mutations of human genes are randomized, challenging neo-Darwinism.

By JERUSALEM POST STAFF Published: JANUARY 31, 2022 19:41

Updated: FEBRUARY 1, 2022 14:37

A DNA double helix is seen in an undated artist's illustration released by the National Human Genome Research Institute to Reuters on May 15, 2012. A group of 25 scientists June 2, 2016, proposed an ambitious project to create a synthetic human genome, or genetic blueprint, in an endeavor that is b
(photo credit: REUTERS/NATIONAL HUMAN GENOME RESEARCH INSTITUTE/HANDOUT)

Is the view by neo-Darwinists, that genetic mutations in human genes are inherently randomized, true? A study by a team of researchers from Israel and Ghana seemingly refutes this argument.

For the past century, an assumption central to Charles Darwin's evolutionary theory is that mutations are random and accidental and that natural selection favors such accidents. In an article published in the scientific peer-reviewed journal Genome Research, see www.Genome-Research-2022.com, researchers have found the first evidence of non-random mutations in human genes.

The Malaria proof

Using a new and innovative method, the researchers - led by the University of Haifa's Prof. Adi Livnat - have managed to prove that the rate of generation of the human hemoglobin S (HbS) mutation which protects one from malaria is higher in people from Africa in contrast to people from Europe. In other words, the mutation is not random but rather exists preferentially within the population of Africa where it is more needed.

Malaria is endemic in Africa, highly common around the entire continent; the more common development of a malaria-resistant mutation specific to the region where it is most needed cannot be explained by the traditional neo-Darwinist theories.

"We hypothesize that evolution is influenced by two sources of information: external information that is natural selection, and internal information that is accumulated in the genome through the generations and impacts the origination of mutations," explained Livnat.

While the theory of evolution is widely accepted in the scientific community, the small details have been put under a microscope for quite some time. For example, there are some impressively quick adaptations of wildlife to their changing surroundings and conditions that suggest that, if natural selection were fully true, the random accidents mentioned earlier were happening at an astonishingly fast pace.

Until now, the only response to this proposed problem was Lamarckism, which claims that the physical changes in organisms which occur during their lifetimes can be passed along genetically to offspring. Since this was not proven to work, the random mutation was maintained as the prominently held belief.

Livnat, alongside lab manager Dr. Daniel Melamed, managed to develop a new record-breakingly accurate method of detecting random mutations which they applied in their research to track the development of the HbS mutation. If random, the mutation should appear relatively equally throughout both Europe and Africa.

Refuting Darwinists' random mutation belief

"Contrary to the widely accepted expectations, the results supported the nonrandom pattern," the University of Haifa announced. "The HbS mutation originated de novo not only much faster than expected from random mutation but also much faster in the population (in sub-Saharan Africans as opposed to Europeans) and in the gene (in the beta-globin as opposed to the control delta-globin gene) where it is of adaptive significance."

These results effectively contradicted the commonly-held random mutation belief held by Darwinists.

“The results suggest that complex information that is accumulated in the genome through the generations impacts mutation, and therefore mutation-specific origination rates can respond in the long-term to specific environmental pressures,” said Prof. Livnat, whose study was funded by a grant given by the John Templeton Foundation. “Mutations may be generated nonrandomly in evolution after all, but not in the way previously conceived. We must study the internal information and how it affects mutation, as it opens the door to evolution being a far bigger process than previously conceived.”

The Livnat study advances Summa Metaphysica's Potentialism Theory

# Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research #
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Darwin was wrong! New study suggests for the first time that genetic mutations are NOT always random and may evolve to respond to environmental pressures

Researchers tracked the appearance of a malaria fighting mutation in genomes
They tracked these mutations throughout populations in Africa and in Europe
The team found the genetic mutation was much more prevalent within Africa
It also evolved much faster than would be expected in individuals and groups
They suggest this means it is a nonrandom mutation in response to environmental factors, in this case to fight of the malaria disease

By RYAN MORRISON FOR DAILYMAIL.COM

PUBLISHED: 16:01 EST, 1 February 2022 | UPDATED: 16:56 EST, 1 February 2022

Darwin's theory that genetic mutations are always random is wrong, suggests a new study which found evidence that mutations can be a response to environmental pressures.

For more than a century, scientists have held to Charles Darwin's theory that all genetic mutations are random and accidental, with the most beneficial traits being passed on through the generations of breeding.

Researchers from the University of Haifa in Israel say that isn't the case, finding that the generation of the human hemoglobin S (HbS) mutation is not random.

People with this mutation have an extra level of protection from malaria, and the team found those in Africa are much more likely to have it than those in Europe.

Study authors say the mutation is not random, as it exists preferentially in Africa, where the protection is more needed, 'something Darwinism can't explain'.

'We hypothesize that evolution is influenced by two sources of information: external information that is natural selection, and internal information that is accumulated in the genome through the generations and impacts the origination of mutations,' explained Professor Adi Livnat, study lead author.

Darwin's theory that genetic mutations are always random is wrong, a new study suggests, finding evidence of mutations in response to environmental pressures. Stock image

This new study, including experts from Ghana, is thought to be the first evidence of 'nonrandom mutations' in human genes.

The findings challenge a core assumption at the heart of Darwin's theory of evolution, showing that a long-term directional mutation response to environmental pressures is possible, and that mutations are not just random phenomena.

'For over a century, the leading theory of evolution has been based on random mutations,' said Professor Livnat.

'The results show that the HbS mutation is not generated at random but instead originates preferentially in the gene and in the population where it is of adaptive significance.'

For more than a century scientists have held to Charles Darwin's theory that all genetic mutations are random and accidental, with the most beneficial traits being passed on through the generations of breeding. Stock image

He suggests that evolution is in fact influenced by two sources of information.

These are external information that is natural selection, and internal information that is accumulated int he genome through the generations.

This second type develops through the generations, and impacts the origination of mutations, according to the researchers.

Darwin told us that life arose by evolution, but exactly how the evolution - at the most granular level - actually works, has been open to discussion and debate.

It has long been assumed it was based on a series of accidental changes to the genome, that through natural selection, saw the strongest mutations survive.

For example, under traditional theories, accidents that lead to larger brains are likely to be passed on, but accidents that cause earlier death, are not.

For example, these accidental mutations led to the hawk developing a sharp eye, to help in the search of prey, and the human cardiovascular system or walking upright.

The big problem with this theory was in the area of 'complexity', according to Professor Livnat, raising questions over whether the accumulation of small, random changes, can create the level of complexity we see in the world around us today.

While each random change might be beneficial, within the millennia timespan, can they interweave complex parts, such as brains, eyes or even wings?

To distinguish between random mutation and natural selection, and adding in the possibility of nonrandom mutations, Professor Livnat created a new method.

This allowed them to detect de novo mutations, which arrive 'out of the blue' in offspring without being inherited from either parent.

The method let them count de novo mutations for particular points of interest within the genome - something not previously possible in such fine detail.

Previous studies have only tested for an immediate mutational response to environmental pressures, and has been limited to measuring mutation rates as an average across a number of positions within the genome.

'Contrary to the widely accepted expectations, the results supported the nonrandom pattern,' the research team wrote.

Researchers from the University of Haifa in Israel say that isn't the case, finding that the generation of the human hemoglobin S (HbS) mutation, that protects against malaria, which is spread by female mosquitos, is not random

The HbS mutation originated de novo much faster than expected from random mutations, but also much faster in the population. They also evolved faster in the gene where it is of adaptive significance.

'The results suggest that complex information that is accumulated in the genome through the generations impacts mutation, and therefore mutation-specific origination rates can respond in the long-term to specific environmental pressures,' said Professor Livnat, speaking to JPost.

'Mutations may be generated nonrandomly in evolution after all, but not in the way previously conceived.

'We must study the internal information and how it affects mutation, as it opens the door to evolution being a far bigger process than previously conceived.'

He said the findings have the potential to change our fundamental understanding of evolution, and diseases that are caused by mutations - including cancer.

This is the second study since the start of the year to suggest nonrandom mutations could be possible, the first looked at a common roadside weed, rather than humans.

In that earlier study, experts from the University of California, Davis, discovered the plant, thale cress, could shield the most essential genes in its DNA from changes.

'The idea of random mutation has been around for over a hundred years in biology and is something you hear so often as a student that it is easy to take it for granted,' lead author Grey Monroe told LiveScience.

'Even as a practicing geneticist and evolutionary biologist, I had never seriously questioned the idea.'

He hasn't claimed their discovery discredits the theory of evolution, and both studies suggest randomness still plays a big role in mutations, however, it isn't the only mechanism at play in evolution.

'In genes coding for proteins essential for survival and reproduction, mutations are most likely to have harmful effects, potentially causing disease and even death,' Monroe said.

'Our results show that genes, and essential genes in particular, experience a lower mutation rate than non-gene regions. The result is that offspring have a lower chance of inheriting a harmful mutation.'

The findings have been published in the journal Genome Research.

+ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research +
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

New study on mutation origination fundamentally challenges neo-Darwinism

Reviewed by Emily Henderson, B.Sc.Jan 31 2022

A new study by a team of researchers from Israel and Ghana has brought the first evidence of nonrandom mutation in human genes, challenging a core assumption at the heart of evolutionary theory by showing a long-term directional mutational response to environmental pressure. Using a novel method, researchers led by Professor Adi Livnat from the University of Haifa showed that the rate of generation of the HbS mutation, which protects against malaria, is higher in people from Africa, where malaria is endemic, than in people from Europe, where it is not. "For over a century, the leading theory of evolution has been based on random mutations. The results show that the HbS mutation is not generated at random but instead originates preferentially in the gene and in the population where it is of adaptive significance," said Prof. Livnat.

Unlike other findings on mutation origination, this mutation-specific response to a specific environmental pressure cannot be explained by traditional theories. "We hypothesize that evolution is influenced by two sources of information: external information that is natural selection, and internal information that is accumulated in the genome through the generations and impacts the origination of mutations," said Livnat.

Ever since Darwin we have known that life arose by evolution. But how, exactly, does evolution – in all its grandeur, mystery and complexity – happen? For the past century scientists have assumed that mutations occur by accident to the genome and that natural selection, or the survival of the fittest, favors beneficial accidents. The accumulation of these presumed genetic accidents under natural selection over the millennia leads in turn to adaptations, from the hawk's sharp eye to the human cardiovascular system.

While widely held in the scientific community, this view has always left open fundamental questions, such as the problem of complexity. Can the sequential accumulation of small random changes, each beneficial on its own, lead within the timespan available to the evolution of such astonishingly complex and impressive adaptations as we see around us in nature, such as eyes, brains or wings, where complementary parts interweave into a complex whole? However, the only alternative at the fundamental level conceived of up until now consisted of variants of Lamarckism – the idea that organisms can somehow respond directly to their immediate environments with beneficial genetic change. Since Lamarckism has not worked in general, the notion of random mutation remained the prevailing view.

In order to distinguish between the random mutation and natural selection explanation and the possibility that nonrandom mutation is important, Prof. Livnat and his lab manager, Dr. Daniel Melamed, developed a new method for detecting de novo mutations – mutations that arise "out of the blue" in offspring without being inherited from either parent. In breaking a new accuracy record, their method allowed something not previously possible – counting of de novo mutations for particular points of interest in the genome.

They then applied their method to examine the de novo emergence of the human hemoglobin S (HbS) mutation, perhaps the most well known point mutation in biology and evolution. HbS provides protection against malaria for people with one copy but causes sickle-cell anemia in those with two. Malaria itself, a vector-borne blood disease, has arguably been the strongest selection pressure acting on humans in the last 10,000 years, often causing more than a million deaths per year in Africa in the recent past. HbS is also used as a central example of random mutation and natural selection in evolution: it has been long assumed to have arisen accidentally in an individual in sub-Saharan Africa and then spread inside Africa via natural selection until its malaria-protective benefits were balanced out by its sickle-cell anemia costs.

By examining the de novo origination of HbS, Livnat was able to disentangle for the first time whether the malaria-protective mutation arises randomly and spread in Africa only because of selection pressure or instead whether it could actually be originating de novo more frequently in sub-Saharan Africans – a group that has been subject to intense malarial selection pressure for many generations. If the mutation is random, then it should be equally likely to emerge in both geographical groups. However, if mutation is nonrandom, then perhaps it would actually emerge more frequently in Africans. "There are at least two possible reasons why such a question had not been asked before," explains Prof. Livnat. "First, it had been assumed that mutation is random. Second, even if one had wanted to ask such a question, it would not have been possible with previous methods."

Contrary to the widely accepted expectations, the results supported the nonrandom pattern. The HbS mutation originated de novo not only much faster than expected from random mutation, but also much faster in the population (in sub-Saharan Africans as opposed to Europeans) and in the gene (in the beta-globin as opposed to the control delta-globin gene) where it is of adaptive significance. These results upend the traditional example of random mutation and natural selection, turning it into an example of a nonrandom yet non-Lamarckian mutation.

Mutations defy traditional thinking. The results suggest that complex information that is accumulated in the genome through the generations impacts mutation, and therefore mutation-specific origination rates can respond in the long-term to specific environmental pressures."

Professor Adi Livnat, University of Haifa

Previous studies, motivated by Lamarckism, only tested for an immediate mutational response to environmental pressures. "Mutations may be generated nonrandomly in evolution after all, but not in the way previously conceived. We must study the internal information and how it affects mutation, as it opens the door to evolution being a far bigger process than previously conceived," Livnat concluded.

Until now, investigators have been limited by technology to measuring mutation rates as averages across many positions in the genome. Overcoming this barrier, the new method developed by Livnat and Melamed allowed the HbS mutation to be the first to have its mutation-specific origination rate measured, opening up new vistas for studies on mutation origination. These studies have the potential to affect not only our fundamental understanding of evolution, but also our understanding of diseases that are caused by mutations, namely genetic disease and cancer.

Source:
University of Haifa

Journal reference:
Melamed, D., et al. (2022) De novo mutation rates at the single-mutation resolution in a human HBB gene-region associated with adaptation and genetic disease. Genome Research. doi.org/10.1101/gr.276103.121.

< Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research <
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Study Uncovers First Evidence Of Long-Term Directionality In Origination Of Human Mutation, Fundamentally Challenging Neo-Darwinism

February 1, 2022 Eurasia Review 0 Comments

By Eurasia Review

“For over a century, the leading theory of evolution has been based on random mutations. The results show that the HbS mutation is not generated at random but instead originates preferentially in the gene and in the population where it is of adaptive significance,” said Prof. Livnat.

Unlike other findings on mutation origination, this mutation-specific response to a specific environmental pressure cannot be explained by traditional theories. “We hypothesize that evolution is influenced by two sources of information: external information that is natural selection, and internal information that is accumulated in the genome through the generations and impacts the origination of mutations,” said Livnat.

In order to distinguish between the random mutation and natural selection explanation and the possibility that nonrandom mutation is important, Prof. Livnat and his lab manager, Dr. Daniel Melamed, developed a new method for detecting de novo mutations – mutations that arise “out of the blue” in offspring without being inherited from either parent. In breaking a new accuracy record, their method allowed something not previously possible – counting of de novo mutations for particular points of interest in the genome.

By examining the de novo origination of HbS, Livnat was able to disentangle for the first time whether the malaria-protective mutation arises randomly and spread in Africa only because of selection pressure or instead whether it could actually be originating de novo more frequently in sub-Saharan Africans – a group that has been subject to intense malarial selection pressure for many generations. If the mutation is random, then it should be equally likely to emerge in both geographical groups. However, if mutation is nonrandom, then perhaps it would actually emerge more frequently in Africans. “There are at least two possible reasons why such a question had not been asked before,” explains Prof. Livnat. “First, it had been assumed that mutation is random. Second, even if one had wanted to ask such a question, it would not have been possible with previous methods.”

“Mutations defy traditional thinking. The results suggest that complex information that is accumulated in the genome through the generations impacts mutation, and therefore mutation-specific origination rates can respond in the long-term to specific environmental pressures,” said Prof. Livnat. Previous studies, motivated by Lamarckism, only tested for an immediate mutational response to environmental pressures. “Mutations may be generated nonrandomly in evolution after all, but not in the way previously conceived. We must study the internal information and how it affects mutation, as it opens the door to evolution being a far bigger process than previously conceived,” Livnat concluded.

> Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research >
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Biologists surprised to discover that some "random" mutations may not be so random

A study into malaria resistance in humans spurs a re-evaluation of the neo-Darwinist understanding of evolution

By Matthew Rozsa Published February 5, 2022 10:00AM (EST)

Evolution of Life on Earth illustration (Getty Images/Man_Half-tube)

A peculiar study into malaria resistance in humans, and where and how it occurs in the population, has unexpectedly spurred a re-evaluation of the neo-Darwinist understanding of evolution.

Neo-Darwinism refers to any branch of science which combines Charles Darwin's theory of evolution by natural selection with Gregor Mendel's discipline of genetics. The overwhelming majority of biologists and geneticists are neo-Darwinists, and one primary tenet of neo-Darwinism is the idea that the genetic mutations which cause living creatures to evolve occur randomly. For humans, this means that mutations from the entirely beneficial (opposable thumbs) and the undesirable (say, those which cause obstructive sleep apnea) can be attributed to chance rather than some kind of purposeful direction. The ones that get passed on permanently do so through natural selection — that is, because they just so happen to help their hosts, who then survive longer and have more opportunities to perpetuate the mutation via reproduction.

At least, that was the prevailing assumption. A new study led by researchers from Israel and Ghana and published in the journal Genome Research reveals that, in fact, at least one helpful genetic mutation was not random at all. They specifically studied the HbS mutation, which protects people against malaria, and found that it arose more frequently within a population where malaria is endemic (Africa) than within a population where it is not (Europe). This might cause some of neo-Darwinism's tenets to be revised.

"The results showed that the malaria resistant HbS mutation arises more frequently in the population and gene where it is of adaptive significance," Dr. Adi Livnat from the University of Haifi, the study's lead researcher and corresponding author, told Salon by email. "This shows empirically for the first time a directional response of mutation to a specific long-term environmental pressure. This sort of result cannot be explained by neo-Darwinism, which is limited to explaining minor, gross-level effects on average mutation rates, not responses of specific mutations to specific environmental pressures. Therefore, the implications are that here there is an empirical finding that neo-Darwinism really cannot explain, which challenges the notion of random mutation on a fundamental level."

Speaking to The Jerusalem Post, Livnat speculated that evolution could actually be shaped by a combination of "external information" through natural selection and "internal information" that is picked up in the human genome from generation to generation and leads to the creation of mutations.

"The research tells us many things, including the fact that the origination rate of the HbS mutation cannot be explained from the perspective of neo-Darwinism," Livnat told Salon.

Livnat and the team of scientists were able to learn something this monumental once they had developed new technology for detecting de novo mutations, meaning those which are not passed down to the child from either parent. With a higher resolution, the scientists were able to count individual novel mutations on specific areas of the genome where they might find something instructive. The human hemoglobin S mutation (HbS) was chosen as their subject of study; neo-Darwinism contends that it originated randomly in a sub-Saharan African individual and spread in that region through natural selection because (despite being associated with sickle-cell anemia) it conferred malaria-protecting benefits. Yet if that theory were accurate, the mutation would still be random and therefore appear in roughly equal numbers between a population that is not heavily exposed to malaria (Europe's) and one that is (Africa's).

This was not the case.

"The HbS mutation originated de novo not only much faster than expected from random mutation but also much faster in the population (in sub-Saharan Africans as opposed to Europeans) and in the gene (in the beta-globin as opposed to the control delta-globin gene) where it is of adaptive significance," the University of Haifa announced in a statement.

In addition, the study gives scientists strong reason to reconsider their current practice of measuring mutation rates as averages across a multitude of positions on the genome.

"We can definitively see that the picture of mutation origination that is obtained once we examine the resolution of specific mutations could not have been expected from traditional theories or previous empirical studies," Livnat explained. "This suggests that most of the signal of mutation rates is not in the averages of mutation rates across many positions but is rather mutation specific. This means that there is an enormous amount of research to be done on how mutations are generated, and that already at the first time mutation origination is observed at this high resolution, we obtain results that challenge the central neo-Darwinian assumption on a fundamental level."

* Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research *
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

ASC scientific discovery: new evidence of the origin of human mutation, Darwin's theory of human evolution may be overturned

2022-02-08 06:21 HKT

Evolution of Life on Earth illustration (Getty Images/Man_Half-tube)

A new study by a team of researchers from Israel and Ghana brings the first evidence of non-random mutations in human genes, challenging core assumptions at the heart of evolutionary theory by showing long-term directed mutational responses to environmental stress. Using a new method, researchers led by Professor Adi Livnat of the University of Haifa have shown that malaria-preventing HbS mutations are generated at higher rates in malaria-endemic Africans than in Europeans, where they are not.

Since Darwin, we have known that life arose by evolution. But how exactly does evolution - in all its grandeur, mystery and complexity - happen? For the past century, scientists have assumed that mutations in the genome occur by chance, and that natural selection, or survival of the fittest, favors beneficial surprises. Over millennia, the accumulation of these putative genetic surprises under natural selection has in turn led to adaptations, from the eagle's keen eyes to the human cardiovascular system.

While widely accepted in the scientific community, this view has always left some fundamental questions unanswered, such as the problem of complexity. Could the successive accumulation of small random changes, each beneficial to itself, lead to such complex and impressive adaptive evolution as we see in nature, such as eyes, brains or wings, within the available time span, Complementary parts intertwined into a complex whole? However, so far, the only alternatives at a fundamental level are variants of Lamarckism - organisms that can respond directly to their immediate environment in some way through beneficial genetic changes. Since Lamarckianism has not generally worked, the concept of random mutation remains the dominant view.

In order to distinguish random mutations from natural selection explanations and the possibility that non-random mutations are important, Professor Livnat and his laboratory manager Dr. Daniel Melamed have developed a new method for detecting de novo mutations - mutations that are "created by the blue" in the offspring color", rather than inheriting from either parent. In breaking a new accuracy record, their method achieved what was not possible before - counting de novo mutations at specific points of interest in the genome.

They then applied their method to examine the de novo emergence of the human hemoglobin S (HbS) mutation, probably the best-known point mutation in biology and evolution. HbS provides protection against malaria in people with only one copy, but causes sickle cell anemia in people with one copy. Malaria itself, a vector-borne blood disease, is arguably the most powerful selection pressure on humans over the past 10,000 years, often killing more than a million people annually in Africa recently. HbS has also been used as a central example of random mutation and natural selection in evolution: it has long been thought to have arisen by chance in individuals in sub-Saharan Africa and then spread within Africa through natural selection until its malaria protective benefits Get to balance the cost of its sickle cell anemia.

"There are at least two possible reasons why such a question has not been asked before," explains Professor Livnat. "First, the mutation is assumed to be random. Second, even if one wanted to ask such a question, it was not possible with previous methods."

Contrary to widely accepted expectations, the results support a non-random pattern. HbS mutation de novo was not only much faster than expected by random mutation, but also in population (in sub-Saharan Africans but not Europeans) and in genes (in β-globin but not in control deltas) much faster-globin gene) has adaptive significance. These results upend the traditional example of random mutation and natural selection, turning it into an example of non-random but non-Lamarckian mutation.

"Mutation goes against conventional thinking. The results show that the complex information accumulated in the genome over several generations influences mutation, so that mutation-specific origin rates can respond to specific environmental stressors in the long term," said Professor Livnat. Previous research, fueled by Lamarckianism, has only tested immediate mutational responses to environmental stress. "Mutations may, after all, arise non-randomly in evolution, but not in the way previously envisioned. We have to look at the internal information and how it affects mutation, because it opens the door to evolution, which is a much larger process than previously envisioned. ," Livnat concluded.

Until now, researchers have been limited to techniques that measure mutation rates as an average over many locations in the genome. Overcoming this hurdle, the new method developed by Livnat and Melamed makes HbS mutation the first to measure its mutation-specific origin rate, opening up new perspectives for mutation origin studies. These studies have the potential to impact not only our fundamental understanding of evolution, but also our understanding of diseases caused by mutations, namely genetic diseases and cancer.

ASC scientific research leads students to immerse themselves in the authentic scientific research courses, curriculum systems and academic advancement of American universities. According to students' academic level and ability, ASC research provides project forms of different degrees of difficulty to help students obtain advancements that meet the corresponding ability level. Improve opportunities.

UNIVERSITY OF WARWICK

On Birnbaum's Formula

from the desk of

Hugo van den Berg

University of Warwick
Department of Mathematics
Coventry, United Kingdom

Mar 28, 2013

"unparalleled and magisterial"

Physics, unlike metaphysics perhaps, is concerned only with description. However, not all descriptions are created equal; it is sometimes possible to capture large swathes of phenomena with a minimum of formal apparatus. Such superb descriptions are what scientists like to think of as “good theories” (all is, in the final analysis, still mere description, a point that is sometimes lost). The game naturally becomes this: to capture as much as possible with as little as possible.

In Birnbaum’s unparalleled and magisterial Summa Metaphysica, we find a pithy quote attributed to a Nobel prize winner [physicist Lederman] who expresses this dream as capturing the universe in a formula that one could print on a T-shirt. Birnbaum, in a staggering and audacious move, displays a formula below this quote.

The formula just stands there, glorious in its splendid isolation. It reads:

Q4P^∞

Are we to infer that this is the answer to the dream of the physicist recently quoted? The recondite renaissance man Birnbaum does not tell us, at least not directly, not on this page.

Perusal of Summa Metaphysica, two imposing tomes of recondite philosophical-mathematical-poetic musings, indicates that Birnbaum wants the reader to think of Q4P as a single symbol......

[ balance of essay upon request ]

Q4P^∞

Q4P ( Q4P ( Q4P (

Quest for Potential ( Quest for Potential ( Quest for Potential
ad infinitum.

/ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research /
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Human genetic mutation may not be random after all, study finds

Groundbreaking study by researchers in Israel and Ghana brings first evidence of nonrandom mutation in human genes.

Israel National News / 01.02.22 / 07:09

Using a novel method, researchers led by Professor Adi Livnat from the University of Haifa showed that the rate of generation of the HbS mutation, which protects against malaria, is higher in people from Africa, where malaria is endemic, than in people from Europe, where it is not. “For over a century, the leading theory of evolution has been based on random mutations. The results show that the HbS mutation is not generated at random but instead originates preferentially in the gene and in the population where it is of adaptive significance,” said Prof. Livnat. Unlike other findings on mutation origination, this mutation-specific response to a specific environmental pressure cannot be explained by traditional theories. “We hypothesize that evolution is influenced by two sources of information: external information that is natural selection, and internal information that is accumulated in the genome through the generations and impacts the origination of mutations,” said Livnat.

In order to distinguish between the random mutation and natural selection explanation and the possibility that nonrandom mutation is important, Prof. Livnat and his lab manager, Dr. Daniel Melamed, developed a new method for detecting de novo mutations – mutations that arise “out of the blue” in offspring without being inherited from either parent. In breaking a new accuracy record, their method allowed something not previously possible – counting of de novo mutations for particular points of interest in the genome.

They then applied their method to examine the de novo emergence of the human hemoglobin S (HbS) mutation, perhaps the most well known point mutation in biology and evolution. HbS provides protection against malaria for people with one copy but causes sickle-cell anemia in those with two. Malaria itself, a vector-borne blood disease, has arguably been the strongest selection pressure acting on humans in the last 10,000 years, often causing more than a million deaths per year in Africa in the recent past. HbS is also used as a central example of random mutation and natural selection in evolution: it has been long assumed to have arisen accidentally in an individual in sub-Saharan Africa and then spread inside Africa via natural selection until its malaria-protective benefits were balanced out by its sickle-cell anemia costs.

By examining the de novo origination of HbS, Livnat was able to disentangle for the first time whether the malaria-protective mutation arises randomly and spread in Africa only because of selection pressure or instead whether it could actually be originating de novo more frequently in sub-Saharan Africans – a group that has been subject to intense malarial selection pressure for many generations. If the mutation is random, then it should be equally likely to emerge in both geographical groups. However, if mutation is nonrandom, then perhaps it would actually emerge more frequently in Africans. “There are at least two possible reasons why such a question had not been asked before,” explains Prof. Livnat. “First, it had been assumed that mutation is random. Second, even if one had wanted to ask such a question, it would not have been possible with previous methods.”

Contrary to the widely accepted expectations, the results supported the nonrandom pattern. The HbS mutation originated de novo not only much faster than expected from random mutation, but also much faster in the population (in sub-Saharan Africans as opposed to Europeans) and in the gene (in the beta-globin as opposed to the control delta-globin gene) where it is of adaptive significance. These results upend the traditional example of random mutation and natural selection, turning it into an example of a nonrandom yet non-Lamarckian mutation.

The article was accepted in the scientific journal Genome Research and appears in an advance online form.

| Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research |
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

New research on mutation development fundamentally challenges neo-Darwinism

Published 1 month ago on February 1, 2022
By NewsDesk

A new study by a team of researchers from Israel and Ghana provides the first evidence of non-random mutations in human genes, and by showing a long-term directional mutation response to environmental pressure, the core of evolution. I challenged the assumption that Researchers led by Professor Adi Livnat of the University of Haifa have shown that malaria-preventing Africans have a higher incidence of malaria-preventing HbS mutations than Europeans, using a new method. I did. Where not. “For more than a century, the main theory of evolution has been based on random mutations. The result is that HbS mutations are not randomly generated, but instead genes and their adaptive importance. It shows that it occurs preferentially in a group. ” Professor Livnat.

Unlike other findings regarding the development of mutations, this mutation-specific response to specific environmental pressures cannot be explained by traditional theory. “We assume that evolution is influenced by two sources: natural selection external information and internal information that accumulates in the genome over generations and influences the development of mutations,” Livnat said. I am.

Since Darwin, we have known that life was caused by evolution. But to be precise, how does evolution occur in all of its grandeur, mystery, and complexity? For the past century, scientists have assumed that mutations are accidental occurrences in the genome, and that natural selection, or survival of the fittest, is beneficial for beneficial accidents. The accumulation of these presumed genetic accidents under thousands of years of natural selection leads to adaptation from the hawk’s sharp eyes to the human cardiovascular system.

While widely supported by the scientific community, this view always leaves behind unsolved fundamental issues, such as the issue of complexity. The continuous accumulation of small random changes, each beneficial in its own right, is astonishing as seen around us in nature such as the eyes, brain, wings, etc., where complementary parts are interwoven. Can you lead within the time available for the evolution of complex and striking adaptations? To the whole complicated? However, the only option at the basic level considered so far consisted of variants of lamarckism. The concept of random mutations remained a common view, as lamarckism is not generally functioning.

To explain random mutation and natural selection, and to distinguish the possibility that non-random mutations are important, Professor Livnat and his laboratory manager, Dr. Daniel Melamed, have developed a new method for detection. did. also Mutations – Mutations that occur “suddenly” in offspring without being inherited by either parent.In breaking the record for new precision, their method enabled something that wasn’t possible before – Count. also Mutations at specific points of interest in the genome.

Then they apply their method, also The emergence of human hemoglobin S (HbS) mutations, perhaps the most well-known point mutations in biology and evolution. HbS provides protection against malaria for people with one copy, but causes sickle cell anemia in people with two copies. Malaria itself, a vector-borne blood disease, is arguably the strongest selection pressure on humans in the last 10,000 years, often killing more than one million people annually in Africa these days. I have. HbS is also used as a central example of random mutation and natural selection in evolution. It has long been thought that it occurred accidentally in sub-Saharan African individuals and spread throughout Africa by natural selection until the malaria protection effect was balanced. Out due to the cost of its sickle cell anemia.

By investigating also For the first time, Livnat, the origin of HbS, was able to determine whether malaria-protective mutations occur randomly and spread to Africa only due to selection pressure, or are actually possible. Outgoing also More often in sub-Saharan Africans – a group that has been exposed to intense malaria selection pressure for generations. If the mutation is random, it should likely appear equally in both geographic groups. But if the mutation is not random, it will probably appear more often in Africans. “There are at least two possible reasons why such a question wasn’t asked before,” explains Professor Livnat. “First, the mutations were supposed to be random. Second, if you wanted to ask such a question, it wasn’t possible with the previous method.”

Contrary to widely accepted expectations, the results supported non-random patterns. HbS mutation occurred also Not only is it much faster than expected from random mutations, but also in populations (sub-Saharan Africans as opposed to Europeans) and genes (beta-globin as opposed to the control deltaglobin gene). Much faster adaptively important. These results overturn the traditional example of random mutation and natural selection and turn it into an example of non-random but non-Lamarck mutations.

Mutations go against traditional thinking. This result suggests that complex information accumulated in the genome throughout generations influences mutations, and therefore mutation-specific incidence may be able to respond to specific environmental pressures in the long term. there is. “

Professor Adi Livnat, University of Haifa

Previous studies motivated by Lamarckism have only been tested for immediate mutational responses to environmental pressure. “Mutations may not be randomly generated in evolution after all, but it’s not the way previously thought. We need to study inside information and how it affects mutations. there is. .

Until now, researchers have been limited by technology to measure mutation rates as an average over many locations in the genome. To overcome this barrier, a new method developed by Livnat and Melamed made it possible to first measure mutation-specific incidence of HbS mutations, opening up new perspectives in research on mutation development. .. These studies can affect not only a basic understanding of evolution, but also an understanding of mutation-induced diseases: genetic and cancer.

\ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research \
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

New study provides first evidence of non-random mutations in DNA

By Harry Baker published January 14, 2022

This goes against one of the key assumptions of the theory of evolution.

An artist's interpretation of a double-stranded helix of DNA. (Image credit: Shutterstock)

Genetic changes that crop up in an organism's DNA may not be completely random, new research suggests. That would upend one of the key assumptions of the theory of evolution.

Researchers studying the genetic mutations in a common roadside weed, thale cress (Arabidopsis thaliana), have discovered that the plant can shield the most "essential" genes in its DNA from the changes, while leaving other sections of its genome to build up more alterations.

"I was totally surprised by the non-random mutations we discovered," lead author Grey Monroe, a plant scientist at the University of California, Davis, told Live Science. "Ever since high-school biology, I have been told that mutations are random."

Random mutations are an important part of the theory of evolution by natural selection, in which mutations give rise to adaptations that are passed on to offspring and alter their chances of survival. Scientists have assumed that these mutations were random and that the first step in evolution by natural selection was, therefore, also random. But this may not be entirely true, the new study suggests.

"The idea of random mutation has been around for over a hundred years in biology and is something you hear so often as a student that it is easy to take it for granted," Monroe said. "Even as a practicing geneticist and evolutionary biologist, I had never seriously questioned the idea."

The new finding does not disprove or discredit the theory of evolution, and the researchers said randomness still plays a big role in mutations. But the study does show that these genetic alterations are more complex than scientists previously believed.

DNA errors

There are plenty of chances for genetic mutations and even errors to occur during the life of an organism.

"DNA is a fragile molecule; on average, the DNA in a single cell is damaged between 1,000 and 1 million times every day," Monroe said. "DNA also has to be copied each time a cell divides, which can introduce copying errors."

Luckily for humans and all other organisms, our cells can counteract a lot of this damage. "Our cells are working constantly to correct DNA and have evolved complex molecular machines, DNA repair proteins, to search for mistakes and make repairs," Monroe said.

However, DNA repair proteins are not a foolproof solution and cannot fix all mistakes. "If damage or copying errors are not repaired, they cause a mutation, a change in the DNA sequence," Monroe said.

There are two main types of mutations: somatic mutations, which cannot be passed on to offspring, and germline mutations, in which offspring can inherit the DNA error from a mutated gene in a parent. Germline mutations are what fuel evolution by natural selection and become more or less common in a population based on how they affect the carrier's ability to survive.

Not all mutations have the potential to alter an organism's chances of survival. Mutations cause major changes to an organism only when they occur in genes — sections of DNA that code for a particular protein. Most of the human genome is made of non-gene DNA, Monroe said.

Non-random pattern

In the new study, researchers decided to test the randomness of mutations by investigating whether mutations were happening evenly between gene and non-gene regions of DNA in the genomes of thale cress.

Thale cress is a "great model organism" for studying mutations because its genome has only around 120 million base pairs (for comparison, the human genome has 3 billion base pairs), which makes it easier to sequence the plant's DNA. It also has a very short life span, which means that mutations can rapidly accumulate across multiple generations, Monroe said.

Over three years, the researchers grew hundreds of plants in laboratory conditions for multiple generations. In total, the researchers sequenced 1,700 genomes and found more than 1 million mutations. But when they analyzed these mutations, they found that the parts of the genomes containing genes had much lower rates of mutation than non-gene regions.

Thale cress (Arabidopsis thaliana) is a "model organism" for studying genetic mutations because of its small genome and short lifespan. (Image credit: Pádraic Flood)

"We think it is likely that other organisms could also have non-random genetic mutations," Monroe said. "We have actually been following up with our study by investigating this question in other species and are finding results that suggest non-random mutation is not unique to Arabidopsis."

However, the researchers suspect that the level of non-randomness among different species may not be the same.

Protecting essential genes

The non-random pattern in mutations between gene and non-gene regions of DNA suggests that there is a defensive mechanism in place to prevent potentially disastrous mutations.

"In genes coding for proteins essential for survival and reproduction, mutations are most likely to have harmful effects, potentially causing disease and even death," Monroe said. "Our results show that genes, and essential genes in particular, experience a lower mutation rate than non-gene regions in Arabidopsis. The result is that offspring have a lower chance of inheriting a harmful mutation."

Researchers found that to protect themselves, essential genes send out special signals to DNA repair proteins. This signaling is not done by the DNA itself but by histones, specialized proteins DNA wraps around to make up chromosomes.

"Based on the result of our study, we found that gene regions, especially for the most biologically essential genes, are wrapped around histones with particular chemical marks," Monroe said. "We think these chemical marks are acting as molecular signals to promote DNA repair in these regions."

The idea of histones having unique chemical markers is not new, Monroe said. Previous studies into mutations in cancer patients have also found that these chemical markers can affect whether DNA repair proteins fix mutations properly, he added.

However, this is the first time these chemical markers have been shown to influence genome-wide mutation patterns and, as a result, evolution by natural selection.

Potential implications

The researchers hope their findings could eventually be used to make improvements in human medicine.

"Mutations affect human health in so many ways, being a cause of cancer, genetic disease and aging," Monroe said. Being able to protect certain regions of the genome from mutations could help prevent or treat these problems, he added.

However, more research into animal genomes is needed before researchers can tell if the same non-random mutations occur in humans. "Our discoveries were made in plants and do not give rise to new treatments," Monroe said, "but they change our fundamental understanding of mutation and inspire many new research directions."

~ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ~
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Scientists disprove one of Darwin's theories

By Natasha Kumar
Feb 4, 2022

Photo: wikipedia.org Charles Darwin

We are talking about the randomness of mutations, as the evolutionist argued. However, a new study has found contradictions in his claim.

Researchers at the University of Haifa in Israel argue that Darwin's theory is flawed in terms of the randomness of mutations. The Daily Mail writes about this.

Scientists have found evidence that the formation of the human hemoglobin S (HbS) mutation is not random. It is also noted that people with this mutation have an additional level of protection against malaria, since it is much higher in Africans than in Europeans.

«We assume that evolution is influenced by two sources of information : external information, which is natural selection, and internal information that accumulates in the genome over generations and affects the occurrence of mutations & # 187;, & # 8212; said the lead author of the study, Professor Adi Livnat.

According to the results of the study, the HbS mutation occurs predominantly in the gene and in the population where it has an adaptive value.

This gene is located on the chromosomes of the cell nucleus, and almost every cell in the human body has the same DNA. S (HbS) consists of four chemical bases: adenine (A), guanine (G), cytosine (C) and thymine (T). At the same time, human DNA consists of three billion bases, and more than 99 percent of them are the same in all people, and the order of their bases determines what information is available to support the body (similar to how the letters of the alphabet form sentences).

DNA bases join together and also attach to a sugar molecule and a phosphate molecule to form nucleotides, which are arranged in two long strands forming a helix called a double helix. It looks like a ladder, with the base pairs forming the rungs and the sugar and phosphate molecules forming the vertical sides.

However, a new form of DNA, called the i-motif, was recently discovered inside living human cells for the first time, more like a twisted «knot» DNA. Experts suggest that its function is for «reading» DNA sequences and converting them into useful substances.

According to traditional theories, accidents that lead to an increase in brain size are likely to be inherited, and accidents that lead to an earlier death &# 8212; no.

To distinguish random mutation from natural selection, as well as to add the possibility of non-random mutations, Professor Livnat created a new method that made it possible to detect de novo mutations that appear in the offspring «unexpectedly». They are also not inherited from either parent.

«Contrary to popular expectation, the results confirm a non-random pattern», — the researchers noted.

In addition, scientists argue that complex information accumulates in the genome over generations and affects mutations, and therefore the rate of occurrence of specific mutations may respond to specific environmental factors in the long term.< /p>

«After all, mutations can occur not by chance in the course of evolution, but not in the way it was previously thought», Professor Livnat said.

Recall that earlier British biologists proved that subspecies of animals do play a key role in their evolution, as Charles Darwin wrote about it.

## Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ##
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Study Reveals Indications of Environmental Sensing by Genetic Apparatus Driving Non-Random Mutation for Directional Adaptation

novo mutation evolution gene mutation human evolution mutation rate natural selection unified spacememory network william brown Feb 22, 2022

By: William Brown, Biophysicist at the Resonance Science Foundation

In our study The Unified Spacememory Network: from cosmogenesis to consciousness, we described how quantum information processing pathways in the molecular genetic system of the biological organism order permutations in a non-random fashion that result in natural directional adaptation and evolution. Information exchanges involving quantum mechanisms at the molecular level of the biological system with the environment and the entanglement nexus of the Spacememory morphogenic field give a kind of natural intelligence to the evolvability of organisms, allowing for meaningful adaptations to occur at an accelerated rate beyond what would be possible under purely random genetic mutations. As the evolutionary biologist Andreas Wagner states, “natural selection can preserve innovations, but it cannot create them… nature’s many innovations, some uncannily perfect, call for natural principles that accelerate life’s ability to innovate” [1].

Such directional gene adaptation had already been observed in experimentations with gene knockout-constructs with the bacteria species E. coli—in which, for example, a gene vital for the metabolism of the sugar lactose is knocked-out or made dysfunctional by introducing a small change in the nucleotide code, when placed in a lactose rich medium, bacteria are observed to “re-activate” the gene, regaining functionality by a purposeful base-change, in a timespan that is accelerated beyond what would occur if changes in the gene were occurring purely randomly [2].

Often a single nucleotide substitution, in this example changing an Adenine residue to a Guanine nucleotide— what is called a single nucleotide polymorphism (SNP)— results in an altered gene product, a protein with a novel functionality, or a dysfunctional protein in the case of disease pathology.

It is almost as if the organisms had some environmental sensing apparatus of the genetic machinery, enabling non-random directional mutation, and demonstrated that selective pressures where not the only factor in determining variational phenotype outcomes, recalling Andreas Wagner’s insight that natural selection is not the only force at play and there must be other natural principles involved that are accelerating the living systems ability to generate innovations via directional adaptations.

Now, in a study conducted through the University of Haifa in Israel and University of Ghana, a team of researchers have found an accelerated rate of an adenine to thymine nucleotide substitution in the human hemoglobin subunit beta (HBB) gene, what is referred to as the hemoglobin S mutation (HbS mutation), which results in substantial protection against severe malaria in heterozygotes (and sickle cell anemia in homozygotes) [3]. The researchers point out that malaria has been the strongest known agent of selection in humans in recent history, as it has been a leading cause of human morbidity and mortality— often causing more than a million deaths per year in the recent past, making this study especially salient for understanding natural selection at the molecular genetic level and possible intrinsic mechanisms of adaptive change.

A single nucleotide substitution results in a SNP, also called a single nucleotide variant (SNV), generating an allele, or variant genetic code. Individuals that have the same SNP from their mother and father are homozygous for that gene loci, whereas SNV sites that are different in the maternal and paternal allele are heterozygous.

The study compared origination rates of target mutations at target base positions in a 6-bp region spanning 3 codons in the HBB gene between genome samples from European and African populations, to assess if environmental pressure from increased rates of malaria infection in endemic regions has any outcome on the rate of de novo (occurring for the first time) mutation in the critical HbS subunit. The study found that the de novo HbS mutation was greatly accelerated—occurred with greater frequency—in the genome samples from African populations, where generation of the allele (gene variant) has much greater adaptive significance than in locales where malaria is not endemic.

"The results show that the HbS mutation is not generated at random but instead originates preferentially in the gene and in the population where it is of adaptive significance,” said Prof. Livnat [of the University of Haifa]. Unlike other findings on mutation origination, this mutation-specific response to a specific environmental pressure cannot be explained by traditional theories. “We hypothesize that evolution is influenced by two sources of information: external information that is natural selection, and internal information that is accumulated in the genome through the generations and impacts the origination of mutations,” said Livnat.

J. Shavit, “Groundbreaking study challenges evolutionary theory, says genetic mutations aren’t always random,” Brighter Side News, Feb. 01, 2022. (accessed Feb. 22, 2022).

The study is significant for molecular genetics in that it is one of the first to measure mutation rates at a specific base pair position within a single gene—because of technological limitations measurement of mutations rates had previously been limited to averages of the entire genome or across the entire stretch of a gene, limiting the resolution of variational rates to large sections of the genome and all but excluding point mutations or entire gene subunits.

Correspondence of HbS allele frequency and incidence of Malaria. The HbS adaptive mutation occurs with a much higher frequency in locations where malaria is endemic. While this allelic distribution would be expected from selective pressures of the environment (natural selection), the researchers in the latest study found that such high frequency occurrence is not only the result of selection pressure, but an internal mechanism of increased de novo mutation in the gene generating the allele variant.

The novel methodology developed by the researchers that enables identifying and counting ultra-rare genetic variants of choice in extremely narrow regions of interest, will allow similar such studies of de novo mutation rates in important gene adaptations that involve single nucleotide substitutions—many such variants that have been exemplars in the study of adaptation by random mutation and natural selection (the conventional model of evolution). As well, the high-resolution knowledge of mutation rates that this novel method enables will allow for detailed studies of recurrent genetic diseases and cancer, allowing for a better understanding of the genetic pathways of these afflictions, and possible mechanisms to mitigate their deleterious occurrence.

The research team states that they do not yet know what mechanisms could be at play to generate increased de novo mutations in this target site that confers adaptive benefits—it is almost as if the genomes of these populations are carrying some kind of memory of the environmental pressures present that enables accelerated adaptive response in target loci (gene sites)—but further high-resolution studies of single nucleotide polymorphism rates across these and other loci and organisms may uncover the molecular mechanisms that are involved.

For our research team here at the Resonance Science Foundation, the study is exciting as it is an empirical validation of the postulate we discussed in the Unified Spacememory Network of directional non-random adaptation and evolution, and whatever the genetic mechanisms that may be at play in generating the non-random response of the gene observed in the study, it may very well be possible that the quantum information pathways we have described are an integral component of the sensing and response apparatus.

References

[1] Wagner A. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. Penguin Group: NY, New York City, 2014.

[2] M. Pigliucci, G.B. Muller, Evolution the Extended Synthesis, pg. 33 – 44, Chance Variation Redux, 2010. The MIT Press, Cambridge, Massachusetts; London, England.

[3] D. Melamed et al., “De novo mutation rates at the single-mutation resolution in a human HBB gene-region associated with adaptation and genetic disease,” Downloaded from genome.cshlp.org on February 22, 2022 - Published by Cold Spring Harbor Laboratory Press.

++ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ++
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

DNA Mutations Are Not Random: New Research Radically Changes Our Understanding of Evolution

TOPICS: DNA Evolution Genetics Plant Science Popular UC Davis

By University of California - Davis January 22, 2022

Studying the genome of thale cress, a small flowering weed, led to a new understanding about DNA mutations. Credit: Pádraic Flood

Findings could lead to advances in plant breeding, human genetics.

A simple roadside weed may hold the key to understanding and predicting DNA mutation, according to new research from University of California, Davis, and the Max Planck Institute for Developmental Biology in Germany.

The findings, published in the journal Nature, radically change our understanding of evolution and could one day help researchers breed better crops or even help humans fight cancer.

Mutations occur when DNA is damaged and left unrepaired, creating a new variation. The scientists wanted to know if mutation was purely random or something deeper. What they found was unexpected.

“We always thought of mutation as basically random across the genome,” said Grey Monroe, an assistant professor in the UC Davis Department of Plant Sciences who is lead author on the paper. “It turns out that mutation is very non-random and it’s non-random in a way that benefits the plant. It’s a totally new way of thinking about mutation.”

Researchers spent three years sequencing the DNA of hundreds of Arabidopsis thaliana, or thale cress, a small, flowering weed considered the “lab rat among plants” because of its relatively small genome comprising around 120 million base pairs. Humans, by comparison, have roughly 3 billion base pairs.

“It’s a model organism for genetics,” Monroe said.

Lab-grown plants yield many variations

Work began at Max Planck Institute where researchers grew specimens in a protected lab environment, which allowed plants with defects that may not have survived in nature be able to survive in a controlled space.

Sequencing of those hundreds of Arabidopsis thaliana plants revealed more than 1 million mutations. Within those mutations a nonrandom pattern was revealed, counter to what was expected.

“At first glance, what we found seemed to contradict established theory that initial mutations are entirely random and that only natural selection determines which mutations are observed in organisms,” said Detlef Weigel, scientific director at Max Planck Institute and senior author on the study.

Instead of randomness they found patches of the genome with low mutation rates. In those patches, they were surprised to discover an over-representation of essential genes, such as those involved in cell growth and gene expression.

“These are the really important regions of the genome,” Monroe said. “The areas that are the most biologically important are the ones being protected from mutation.”

The areas are also sensitive to the harmful effects of new mutations. “DNA damage repair seems therefore to be particularly effective in these regions,” Weigel added.

Plant evolved to protect itself

The scientists found that the way DNA was wrapped around different types of proteins was a good predictor of whether a gene would mutate or not. “It means we can predict which genes are more likely to mutate than others and it gives us a good idea of what’s going on,” Weigel said.

The findings add a surprising twist to Charles Darwin’s theory of evolution by natural selection because it reveals that the plant has evolved to protect its genes from mutation to ensure survival.

“The plant has evolved a way to protect its most important places from mutation,” Weigel said. “This is exciting because we could even use these discoveries to think about how to protect human genes from mutation.”

Future uses

Knowing why some regions of the genome mutate more than others could help breeders who rely on genetic variation to develop better crops. Scientists could also use the information to better predict or develop new treatments for diseases like cancer that are caused by mutation.

“Our discoveries yield a more complete account of the forces driving patterns of natural variation; they should inspire new avenues of theoretical and practical research on the role of mutation in evolution,” the paper concludes.

For more on this discovery, see DNA Mutations Do Not Occur Randomly.

Reference: “Mutation bias reflects natural selection in Arabidopsis thaliana” by J. Grey Monroe, Thanvi Srikant, Pablo Carbonell-Bejerano, Claude Becker, Mariele Lensink, Moises Exposito-Alonso, Marie Klein, Julia Hildebrandt, Manuela Neumann, Daniel Kliebenstein, Mao-Lun Weng, Eric Imbert, Jon Ågren, Matthew T. Rutter, Charles B. Fenster and Detlef Weigel, 12 January 2022, Nature.
DOI: 10.1038/s41586-021-04269-6

Co-authors from UC Davis include Daniel Kliebenstein, Mariele Lensink, Marie Klein, from the Department of Plant Sciences. Researchers from the Carnegie Institution for Science, Stanford University, Westfield State University, University of Montpellier, Uppsala University, College of Charleston, and South Dakota State University contributed to the research.

Funding came from the Max Planck Society, the National Science Foundation and the German Research Foundation.

<< Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research <<
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Beating the odds in mutation’s game of chance

Discovery that plants protect their most essential genes transforms our view of evolution

January 12, 2022

Mutations of DNA do not occur as randomly as preciously assumed, according to new research from Max Planck Institute for Biology Tübingen in Germany and University of California Davis in the US. The findings have the potential to dramatically change our view of evolution. The insights have far-reaching implications, from better knowledge of crop domestication to predictions of the mutational landscape in cancers.

Photo: wikipedia.org Charles Darwin

Mutations, which occur when DNA is damaged and left unrepaired, are the major fuel of evolution. A central assumption of Darwin’s theory of evolution is that they arise randomly, and that only natural selection determines which genes change more quickly and which more slowly in the course of evolution. This core assumption has now been upended. “We always thought of mutations appearing solely by chance across the genome,” says Grey Monroe, an assistant professor in the UC Davis Department of Plant Sciences and first author of the paper. “It now turns out that the pattern of mutation is not only very non-random, but also that it’s non-random in a way that benefits the plant.” “This is a completely novel perspective on mutation and the way evolution works,” comments Detlef Weigel, scientific director at the Max Planck Institute for Biology and senior author of the study.

Protecting plants with harmful mutations

Researchers grew specimens of the widely distributed weed Arabidopsis thaliana in a sheltered lab environment, where all plants, including ones with harmful mutations, could reproduce. Such harmful mutations would normally be quickly removed by the selection pressures that prevail in nature and therefore disappear before they could be observed. By analyzing the genomes of hundreds of lab grown plants, the scientist could identify thousands of mutations as they arose.

Sophisticated statistical analyses revealed that these mutations were by no means randomly distributed in the genome, as the researchers had expected. Instead, they found stretches of the genome where mutations were rare, and others where mutations were much more common. In those regions with few mutations, genes needed in every cell and thus essential for the survival of every plant were greatly overrepresented. “These are regions of the genome most sensitive to harmful effects of new mutations,” Weigel says, “and DNA damage repair seems therefore to be particularly effective in these regions.” It is as if evolution were playing with loaded dice – it minimizes the risk of damaging the most vital genes.

A new perspective on classical evolutionary theory

The scientists found that the different types of proteins around which DNA is wrapped in the cell nucleus are highly correlated with the appearance of mutations. “It gives us a good idea of what’s going on, so that we can predict which genes are more likely to mutate than others,” Monroe says.

Weigel stressed how entirely unexpected the results were in the light of classical evolutionary theory: “It has long been known that during the course of evolution certain regions of the genome accumulate more mutations than other regions do. At first glance, what we found seemed to contradict accepted wisdom that this just reflects natural selection removing most mutations before they can actually be observed,” he explains. However, despite the uneven distribution of mutations in a typical genome, the important regions are not entirely devoid of them, and these regions can therefore also evolve, although at a slower pace than other parts of the genome.

Future uses in breeding and medical research

“The plant has evolved a way to protect its most important genes from mutation,” Monroe says. “This is exciting because we could even use these discoveries to think about how to protect human genes from mutation.” In the future, one might use them to predict which genes are best targets for breeding because they evolve fast, or which are most likely to cause disease in humans.

Most of the work was carried out at the Max Planck Institute for Biology (formerly the Max Planck Institute for Developmental Biology), and it is now being continued both there and at UC Davis. Researchers from the Carnegie Institution for Science, Stanford University, Westfield State University, University of Montpellier, Uppsala University, College of Charleston, and South Dakota State University also contributed to the work. Funding came from the Max Planck Society, with additional funding from the National Science Foundation and the German Research Foundation.

The Adi Livnat Gene Study

Are genetic mutations random in humans? Israeli study says no

A study by the University of Haifa researchers claims not all genetic mutations of human genes are randomized, challenging neo-Darwinism.

The Malaria proof

Refuting Darwinists' random mutation belief

The Livnat study advances Summa Metaphysica's Potentialism Theory

Fully Synchronous

# Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research # * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Darwin was wrong! New study suggests for the first time that genetic mutations are NOT always random and may evolve to respond to environmental pressures

+ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research + * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

New study on mutation origination fundamentally challenges neo-Darwinism

< Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research < * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Study Uncovers First Evidence Of Long-Term Directionality In Origination Of Human Mutation, Fundamentally Challenging Neo-Darwinism

> Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research > * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Biologists surprised to discover that some "random" mutations may not be so random

A study into malaria resistance in humans spurs a re-evaluation of the neo-Darwinist understanding of evolution

* Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research * * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

ASC scientific discovery: new evidence of the origin of human mutation, Darwin's theory of human evolution may be overturned

David Birnbaum Cracks the Cosmic Code

On Birnbaum's Formula

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/ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research / * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Human genetic mutation may not be random after all, study finds

Groundbreaking study by researchers in Israel and Ghana brings first evidence of nonrandom mutation in human genes.

| Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research | * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

New research on mutation development fundamentally challenges neo-Darwinism

\ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research \ * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

New study provides first evidence of non-random mutations in DNA

This goes against one of the key assumptions of the theory of evolution.

DNA errors

Non-random pattern

Protecting essential genes

Potential implications

~ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ~ * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Scientists disprove one of Darwin's theories

We are talking about the randomness of mutations, as the evolutionist argued. However, a new study has found contradictions in his claim.

## Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ## * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Study Reveals Indications of Environmental Sensing by Genetic Apparatus Driving Non-Random Mutation for Directional Adaptation

References

++ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ++ * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

DNA Mutations Are Not Random: New Research Radically Changes Our Understanding of Evolution

Findings could lead to advances in plant breeding, human genetics.

Lab-grown plants yield many variations

Plant evolved to protect itself

Future uses

<< Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research << * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Beating the odds in mutation’s game of chance

Protecting plants with harmful mutations

A new perspective on classical evolutionary theory

Future uses in breeding and medical research

>> Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research >> * non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence * * directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Are genetic mutations random in humans?
Israeli study says no

# Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research #
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

+ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research +
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

< Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research <
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

> Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research >
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

* Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research *
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

Q4P^∞

Q4P^∞

/ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research /
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

| Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research |
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

\ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research \
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

~ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ~
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

## Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ##
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

++ Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research ++
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

<< Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research <<
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *

>> Livnat Gene Study * University of Haifa, Israel * Ghana hemoglobin mutation research >>
* non-random gene, DNA mutations evolution * Malaria-fighting genetic mutation evidence *
* directional evolution evidence * fundamentally challenging random neo-Darwinism theory *