Evidence for germline non-genetic inheritance of human phenotypes and diseases

Phenotypes can be inherited in a DNA-independent manner

https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00929-y

Excerpt: "It is becoming increasingly apparent that certain phenotypes are inherited across generations independent of the information contained in the DNA sequence, by factors in germ cells that remain largely uncharacterized. As evidence for germline non-genetic inheritance of phenotypes and diseases continues to grow in model organisms, there are fewer reports of this phenomenon in humans, due to a variety of complications in evaluating this mechanism of inheritance in humans. This review summarizes the evidence for germline-based non-genetic inheritance in humans, as well as the significant challenges and important caveats that must be considered when evaluating this process in human populations. Most reports of this process evaluate the association of a lifetime exposure in ancestors with changes in DNA methylation or small RNA expression in germ cells, as well as the association between ancestral experiences and the inheritance of a phenotype in descendants, down to great-grandchildren in some cases. Collectively, these studies provide evidence that phenotypes can be inherited in a DNA-independent manner; the extent to which this process contributes to disease development, as well as the cellular and molecular regulation of this process, remain largely undefined.

The traditional Mendelian model of inheritance states that phenotypes are inherited based on the transmission of DNA sequences across generations, and diseases are inherited when these DNA sequences are abnormal. In model organisms, it is becoming increasingly apparent that phenotypes and disease risk can be inherited from sperm and oocytes in the absence of DNA mutations or variations. This non-genetic inheritance is based on the concept that non-DNA molecules in sperm and oocytes are inherited at fertilization and modify the phenotype of the offspring, sometimes across multiple generations. The central concept in this field is that an organism’s exposures (diet, stress, chemicals, etc.) affect the composition of germline non-DNA molecules, and in this manner, these exposures can affect phenotypes in descendants. Localization of this phenomenon to the germ cells is proven by the use of in vitro fertilization with surrogate “mothers” carrying the fetus who never experienced the exposure. While there are multiple examples of this phenomenon across a variety of model organisms, the role of this process in human inheritance is less well described, and the cellular and molecular mechanisms that drive the non-genetic inheritance of phenotypes across generations are similarly poorly characterized.This process is often referred to as “epigenetic inheritance.”

Epigenetics refers to the modification of a phenotype without a change to the DNA sequence itself, and epigenetic factors are specific molecules that affect gene expression without changing the DNA sequence; examples include DNA methylation and chromatin modifications. In sperm and oocytes, these epigenetic molecules can be inherited at fertilization and thereby affect fetal organ development by modifying patterns of gene expression. These germline epigenetic factors are potentially altered based on an individual’s experiences and exposures, and in this manner, epigenetic abnormalities in sperm and oocytes can have significant effects on a descendant’s risk of disease. The germline factors discussed here include DNA methylation and small RNAs. DNA methylation is the covalent addition of a methyl group to DNA, which often leads to gene silencing. Small RNAs are a diverse group of molecules that do not code for protein; rather they have diverse (and in some cases, poorly understood) functions including the modulation of gene expression. Small RNAs are not traditional epigenetic molecules because they mostly target RNA molecules rather than DNA, and are therefore more accurately described as post-transcriptional gene expression regulators. Examples of small RNAs include miRNA, piRNA, snoRNA, and tRNA-derived fragments. Histone modifications are another common epigenetic modification which is not discussed in this review because their role in germline-mediated inheritance is largely undescribed, due to the epigenetic reprogramming that characterizes germ cell development (see below). While epigenetic factors are important contributors to inherited phenotypes caused by ancestral exposures in model organisms, their role in human exposure-driven inheritance is undescribed; thus, we use the term “non-genetic inheritance” to describe this process in humans.
"

Coronavirus is not evolving

None of the 12,706 mutations in SARS-CoV-2 is beneficial - evolution is not happening

https://www.labmanager.com/news/sars-cov-2-mutations-dont-appear-to-increase-transmissibility-24495

Excerpt:"None of the mutations currently documented in the SARS-CoV-2 virus appear to increase its transmissibility in humans, according to a study led by University College London (UCL) researchers.

The analysis of virus genomes from over 46,000 people with COVID-19 from 99 countries was published Nov. 25 in Nature Communications.

First and corresponding author Dr. Lucy van Dorp (UCL Genetics Institute) said: "The number of SARS-CoV-2 genomes being generated for scientific research is staggering. We realized early on in the pandemic that we needed new approaches to analyze enormous amounts of data in close to real time to flag new mutations in the virus that could affect its transmission or symptom severity.

Fortunately, we found that none of these mutations are making COVID-19 spread more rapidly, but we need to remain vigilant and continue monitoring new mutations, particularly as vaccines get rolled out."

Coronaviruses like SARS-CoV-2 are a type of RNA virus, which can all develop mutations in three different ways: by mistake from copying errors during viral replication, through interactions with other viruses infecting the same cell (recombination or reassortment), or they can be induced by host RNA modification systems which are part of host immunity (e.g. a person's own immune system).

Most mutations are neutral, while others can be advantageous or detrimental to the virus. Both neutral and advantageous mutations can become more common as they get passed down to descendant viruses.
 

The research team from UCL, Cirad and the Université de la Réunion, and the University of Oxford, analyzed a global dataset of virus genomes from 46,723 people with COVID-19, collected up until the end of July 2020.

The researchers have so far identified 12,706 mutations in SARS-CoV-2, the virus causing COVID-19. For 398 of the mutations, there is strong evidence that they have occurred repeatedly and independently. Of those, the researchers honed in on 185 mutations which have occurred at least three times independently during the course of the pandemic.To test if the mutations increase transmission of the virus, the researchers modeled the virus's evolutionary tree, and analyzed whether a particular mutation was becoming increasingly common within a given branch of the evolutionary tree—that is, testing whether, after a mutation first develops in a virus, descendants of that virus outperform closely-related SARS-CoV-2 viruses without that particular mutation.

The researchers found no evidence that any of the common mutations are increasing the virus's transmissibility. Instead, they found most common mutations are neutral for the virus. This includes one mutation in the virus spike protein called D614G, which has been widely reported as being a common mutation that may make the virus more transmissible. The new evidence finds that this mutation is in fact not associated with significantly increasing transmission.

The researchers found that most of the common mutations appear to have been induced by the human immune system, rather than being the result of the virus adapting to its novel human host. This situation is in contrast with another analysis by the same team of what happened when SARS-CoV-2 later jumped from humans into farmed minks.

Van Dorp said: "When we analyzed virus genomes sourced from mink, we were amazed to see the same mutation appearing over and again in different mink farms, despite those same mutations having rarely been observed in humans before."

Lead author and professor Francois Balloux (UCL Genetics Institute) added: "We may well have missed this period of early adaptation of the virus in humans. We previously estimated SARS-CoV-2 jumped into humans in October or November 2019, but the first genomes we have date to the very end of December. By that time, viral mutations crucial for the transmissibility in humans may have emerged and become fixed, precluding us from studying them."

It is only to be expected that a virus will mutate and eventually diverge into different lineages as it becomes more common in human populations, but this does not necessarily imply that any lineages will emerge that are more transmissible or harmful.

Van Dorp said: "The virus seems well adapted to transmission among humans, and it may have already reached its fitness optimum in the human host by the time it was identified as a novel virus."

The researchers caution that the imminent introduction of vaccines is likely to exert new selective pressures on the virus to escape recognition by the human immune system. This may lead to the emergence of vaccine-escape mutants. The team stressed that the computational framework they developed should prove useful for the timely identification of possible vaccine-escape mutations.
Balloux concluded: "The news on the vaccine front looks great. The virus may well acquire vaccine-escape mutations in the future, but we're confident we'll be able to flag them up promptly, which would allow updating the vaccines in time if required.""

My comment: The Sars-Cov-2 virus carries an proofreading enzyme called exoribonuclease in its toolbox by which it is able to repair most of mutations during its transmissions between organisms. However, thousands of mutations have already been identified and none of them is beneficial for the virus. Even the famous D614G mutation seems not to be beneficial.

Interesting is that human immune system is modulating the Sars-Cov-2 genome. This same phenomenon seems occurring in mink farms in different locations; same mutations are appearing and this confirms the view that most of the mutations are not random changes but induced by immune systems. The coronavirus is slowly experiencing a critical amount of mutations and it will die down, maybe after several years though. There are other mechanisms by which it's is able to adapt to changing environments and probably escape vaccines. These are RNA epigenetic modifications. 

The Sars-Cov-2 RNA virus contains ~30,000 nucleotides and it has several overlapping (embedded genes or 'genes inside genes') genes. It's a single stranded RNA virus and human cells will not store its sequence in our genomes. 

Biology textbooks were wrong again

If transcription were not controlled, nothing would work - and life would be impossible

https://scitechdaily.com/biology-textbooks-wrong-new-research-reveals-the-secret-behind-a-key-cellular-process/

For the first time, researchers describe how Rho protein really stops gene expression.

Excerpt: "New research has identified and described a cellular process that, despite what textbooks say, has remained elusive to scientists until now — precisely how the copying of genetic material that, once started, is properly turned off.

The finding concerns a key process essential to life: the transcription phase of gene expression, which enables cells to live and do their jobs.

During transcription, an enzyme called RNA polymerase wraps itself around the double helix of DNA, using one strand to match nucleotides to make a copy of genetic material — resulting in a newly synthesized strand of RNA that breaks off when transcription is complete. That RNA enables production of proteins, which are essential to all life and perform most of the work inside cells.

Just as with any coherent message, RNA needs to start and stop in the right place to make sense. A bacterial protein called Rho was discovered more than 50 years ago because of its ability to stop, or terminate, transcription. In every textbook, Rho is used as a model terminator that, using its very strong motor force, binds to the RNA and pulls it out of RNA polymerase. But a closer look by these scientists showed that Rho wouldn’t be able to find the RNAs it needs to release using the textbook mechanism.

“We started studying Rho, and realized it cannot possibly work in ways people tell us it works,” said Irina Artsimovitch, co-lead author of the study and professor of microbiology at The Ohio State University.

The research, published online by the journal Science today, November 26, 2020, determined that instead of attaching to a specific piece of RNA near the end of transcription and helping it unwind from DNA, Rho actually “hitchhikes” on RNA polymerase for the duration of transcription. Rho cooperates with other proteins to eventually coax the enzyme through a series of structural changes that end with an inactive state enabling release of the RNA.

The team used sophisticated microscopes to reveal how Rho acts on a complete transcription complex composed of RNA polymerase and two accessory proteins that travel with it throughout transcription.

“This is the first structure of a termination complex in any system, and was supposed to be impossible to obtain because it falls apart too quickly,” Artsimovitch said.

“It answers a fundamental question — transcription is fundamental to life, but if it were not controlled, nothing would work. RNA polymerase by itself has to be completely neutral. It has to be able to make any RNA, including those that are damaged or could harm the cell. While traveling with RNA polymerase, Rho can tell if the synthesized RNA is worth making — and if not, Rho releases it.”

Artsimovitch has made many important discoveries about how RNA polymerase so successfully completes transcription. She didn’t set out to counter years of understanding about Rho’s role in termination until an undergraduate student in her lab identified surprising mutations in Rho while working on a genetics project.

Rho is known to silence the expression of virulence genes in bacteria, essentially keeping them dormant until they’re needed to cause infection. But these genes do not have any RNA sequences that Rho is known to preferentially bind. Because of that, Artsimovitch said, it has never made sense that Rho looks only for specific RNA sequences, without even knowing if they are still attached to RNA polymerase.

In fact, the scientific understanding of the Rho mechanism was established using simplified biochemical experiments that frequently left out RNA polymerase — in essence, defining how a process ends without factoring in the process itself.
 

In this work, the researchers used cryo-electron microscopy to capture images of RNA polymerase operating on a DNA template in Escherichia coli, their model system. This high-resolution visualization, combined with high-end computation, made accurate modeling of transcription termination possible.

“RNA polymerase moves along, matching hundreds of thousands of nucleotides in bacteria. The complex is extremely stable because it has to be — if the RNA is released, it is lost,” Artsimovitch said. “Yet Rho is able to make the complex fall apart in a matter of minutes, if not seconds. You can look at it, but you can’t get a stable complex to analyze.”

Using a clever method to trap complexes just before they fall apart enabled the scientists to visualize seven complexes that represent sequential steps in the termination pathway, starting from Rho’s engagement with RNA polymerase and ending with a completely inactive RNA polymerase. The team created models based on what they saw, and then made sure that these models were correct using genetic and biochemical methods.

Though the study was conducted in bacteria, Artsimovitch said this termination process is likely to occur in other forms of life.
“It appears to be common,” she said. “In general, cells use similar working mechanisms from a common ancestor. They all learned the same tricks as long as these tricks were useful.”"

Summary and conclusions:

• Rho actually “hitchhikes” on RNA polymerase for the duration of transcription. This means it monitors and controls the entire transcriptional procedure.
• If the Rho monitoring and controlling mechanism doesn't work, protein production will fail, the cell is not able to live and life is not possibe.
• How could the Rho mechanism then have been evolved??? It's clear that this mechanism has to exist fully working in order to the cell being able to live.
• Textbooks are wrong about evolution.

Flightless birds are hard evidence against evolution

Several birds have lost their ability to fly due to genetic mutations - Genetic erosion is a biological fact

https://www.sciencemag.org/news/2017/06/how-clumsy-galapagos-cormorant-lost-its-flight

Excerpt:"Fernandina, the westernmost island in the Galapagos archipelago, is a pristine spot. It is also a place regularly inundated by lava flows that set its waters boiling. Yet that hasn’t stopped one odd bird from calling Fernandina home: the world’s only flightless cormorant. Now, a new study proposes an explanation for how the stumpy-winged seabird lost its ability to fly—through more than a dozen genetic anomalies that it shares with humans suffering from a variety of rare skeletal disorders.

Since many developmental genes shoulder multiple roles, Kruglyak’s team reasoned that a genetic factor for flightlessness would not be found in a protein mutation, which could lead to a fatal outcome. Instead, they began searching for irregularities in the vast segments of DNA between genes called the noncoding regions, hoping to find clues about how the same genes might be regulated differently.

But that comparison yielded no results, so they turned back to the coding regions—the genes that produce proteins—to search for mutations that would change a protein’s ability to function normally. They discovered about a dozen mutated genes in the Galapagos cormorants known to trigger rare skeletal disorders in humans called ciliopathies, often characterized by misshapen skulls, short limbs, and small ribcages. Since Galapagos cormorants have short wings and an unusually small sternum, the researchers suspected this link was significant, they write today in Science.

Ciliopathies in humans arise from gene mutations affecting cilia—the microscopic hairlike extensions used to convey chemical messages between cells that control vertebrate development. When those signals go off-kilter, the body can grow in a visibly abnormal way. Sensenbrenner syndrome is one example, a rare condition reported in only a few dozen people characterized by an elongated skull, short limbs and fingers, a narrow chest, and respiratory problems. One of the genes linked to Sensenbrenner, called Ift122, was similarly mutated in the Galapagos cormorant. Another gene responsible for cilia production, Cux1, seemed to play a role in the cormorant’s stubby wings."

https://www.darwinthenandnow.com/archives/8666/galapagos-icon-of-evolution/

Excerpt: "Darwin, however, may have never seen the flightless Galapagos cormorants. During his five-year global expedition, while Darwin only mentions the cormorants (pictured) five-times in his Voyage of the Beagle, but during his thirty-five-day survey of the Galapagos Islands in 1835, the flightless cormorant is never mentioned."

My comment: It's very likely that Galápagos cormorants have lost their ability to fly just recently.

Known examples of flightless birds:

Emu

Ostrich

Rhea

Penguin

Cassowary

Kiwi

Kagu

Takahe

Weka

Steamer duck

Red junglefowl

Flightless cormorant

My comment: There is no evidence that assumed evolution could produce novel structures. How could a random chance develop an ability to fly? The theory of evolution has no scientific basis. Instead, we can observe rapid genetic degradation that can be called devolution. Most of these flightless birds are classified as critically endangered or vulnerable according to IUCN red list. 

Diamonds created in minutes at room temperature

Diamonds can actually form at room temperature, under the right pressure

https://www.advancedsciencenews.com/diamonds-created-in-minutes-at-room-temperature/

Excerpt: "Diamonds are highly coveted the world over, forming naturally in the Earth’s mantle under extreme temperature and pressure over billions of years. Now, a team of scientists from the Australian National University (ANU) and the Royal Melbourne Institute of Technology (RMIT) University have reported a means of making the gemstones at room temperature within a matter of minutes.

Beauty aside, diamonds are highly useful materials — especially within the realm of technology — due to their extreme hardness, high thermal conductivity, and quantum optical properties. To overcome the issues of their availability and cost, the first synthetic diamonds were produced in the early 1950s for industrial use.
While a faster means of obtaining the gems, these synthetic procedures still require high pressure and temperature to turn elemental carbon into crystalline diamond; this is because the energy required to overcome the high kinetic barrier between carbon’s material phases is extremely high.

In their current study recently published in Small, the team of researchers led by Professor Dougal G. McCulloch reported the formation of nanocrystalline diamond and lonsdaleite — a less common form of carbon with a hexagonal crystal structure — at room temperature using a pressure of 80 GPa. This is a substantial improvement seeing as most procedures require temperatures of roughly 1400 °C.

The “twist” comes from how the pressure was applied. Glassy carbon was used as the precursor material, and was compressed in diamond anvil cells at room temperature. “Glassy carbon is a non‐crystalline form of carbon, which, like graphite, is predominantly sp2 bonded, but unlike graphite, contains randomly stacked and oriented layers to form an opaque, isotropic material,” they said.

Using transmission electron microscopy (TEM), the researchers analyzed intact samples recovered from the cells, which they say allowed them to provide a more complete understanding of the nature and relationship between phases present in the recovered material. “This is akin to sampling a rock core instead of crushed powder samples, and [allowed] us to investigate the atomic level relationships between the arrangement of crystallographic phases present and the non‐uniform stress field present in the diamond anvil cell,” they wrote.

After compressing the glassy carbon and analyzing the samples, three distinct phases of carbon were observed: graphite, diamond, and lonsdaleite.

“Diamond and lonsdaleite are generally thought to form via different transformation pathways involving the sliding of graphene layers […] to achieve the appropriate stacking as the layers are compressed together,” said the authors. This displacement of atoms required to form their respective crystalline forms is generally achieved by heating the sample to minimize the kinetic barrier that exists between phases.

The presence of nanocrystalline diamond and lonsdaleite veins in their samples — miraculously obtained without heating — could only be explained by the presence of high pressure and shear strain, which results in a twisting and sliding force that helps in overcoming the phase change’s kinetic barriers.
“We anticipate that our observation of shear‐induced phase transformations in carbon has widespread implications in a range of fields including materials science, geology and planetary science, where this mechanism may lead to phase changes in other solids,” concluded the authors. This could also have implications in terms of where diamond is likely to be found, both on Earth and on other planets, as the conditions for its formation just became a little broader."

Reference: Dougal G. McCulloch, et al., Investigation of Room Temperature Formation of the Ultra‐Hard Nanocarbons Diamond and Lonsdaleite, Small (2020). DOI: 10.1002/smll.202004695

My comment: Seems that there is no need for millions of years in order to diamonds to form.

Back to the Galápagos Islands - To understand what Darwin didn't understand

Rapid adaptation of Darwin's Finches has nothing to do with evolution

https://www.forbes.com/sites/grrlscientist/2017/09/06/how-do-darwins-finches-respond-so-quickly-to-environmental-changes/?sh=4813f3885810

Excerpt: "Epigenetics may be how Darwin’s finches rapidly change their beak size and shape in response to sudden environmental changes, such as drought or human disturbance, in the absence of gene mutations.

How does a population adapt to sudden changes in the environment? According to the most widely accepted paradigm, random genetic changes (mutations) are the source of heritable changes in a plant or animal’s observable characteristics (phenotype). Phenotype, in turn, is the raw material that is acted upon by natural selection, and the most beneficial adaptations are passed on to successive generations. But there is a problem with this paradigm: adaptive genetic mutations are so infrequent that this scenario cannot adequately explain the speed at which adaptation can occur.

One well-known example of speedy adaptation is seen in “Darwin’s finches”; a group of approximately 15 bird species that live in the Galápagos Islands Archipelago, which are located on the equator in the Pacific Ocean. Ongoing field studies have documented rapid changes in these birds’ beak sizes and shapes in response to sudden environmental variations -- drought, or human disturbances, for example -- yet very few genetic changes have been found that accompany those physical differences between finch species, nor between populations (ref). What guides these important changes and the speed which they can occur in these iconic birds?

The process of adaptation is more subtle than originally thought

Scientists have recently become aware that adaptation is not solely dependent upon genetic mutations; it can also occur through “extra-genetic” mechanisms. At least some changes in gene function and expression patterns are independent of mutations in a gene’s DNA sequence, yet these changes may still be inherited (ref). These alterations are known as “epigenetic changes” (epi comes from the Greek, and translates as “over, outside of, around”) because these changes are in addition to changes in the DNA sequence itself. Epigenetic changes can activate or intensify, lessen or even completely silence, the activity of a particular gene without changing its DNA sequence.

Epigenetic changes can be triggered by environmental events. The changes that dominate alterations in gene expression and function are biochemical in nature, including: addition of a biochemical tag (methylation) to DNA; addition of a biochemical tag (methylation or acetylation) to the histone proteins around which DNA spools; or regulation of gene expression patterns by small RNA molecules.

Probably the most common epigenetic modification is DNA methylation, and just as genetic mutations can be heritable, DNA methylation patterns can be heritable, too. For example, previous work found that some epigenetic variations in five closely related species of Darwin’s finches accompany genes associated with beak size and shape, as well as a number of other important physical traits (ref). We also know that changes in DNA methylation patterns are more common than DNA mutations. Based on these clues, a team of researchers, led by evolutionary ecologist Sabrina McNew, a graduate student at the University of Utah, proposed that epigenetic mutations -- NOT genetic mutations -- may explain how Darwin’s finches rapidly adapt to new or highly variable environments, such as those created by urbanization.

“Darwin’s finches are known for being phenotypically very variable, yet [they are] genetically pretty similar,” Ms. McNew explained in email.

“We were interested in investigating epigenetic variation between urban and rural populations [of Darwin’s finches] because other exciting recent work suggests that epigenetic mechanisms, such as DNA methylation can be a source of heritable phenotypic variation.”

Are epigenetics the secret to Darwin’s finches’ speedy adaptation?

To test this hypothesis, Ms. McNew assembled a research team and they measured physical traits (morphology) of wild birds in the field, and examined both the genetics and the epigenetics of separate populations of two Darwin’s finch species living at El Garrapatero, a relatively rural, undisturbed locality. They compared these findings to those from urban finch populations living near Puerto Ayora (Academy Bay), the largest town in the Galápagos Islands.

The rural and urban study sites are separated by about 10km. Earlier long-term studies (2002–2012) established that the birds in these two finch populations stay put: only one bird (a female medium ground finch) out of 300 marked and recaptured individuals relocated between the two study sites in one decade.

“[T]he finches tend to be fairly sedentary and so we think that most of the birds we caught probably grew up at whichever site they were caught at and probably their parents lived there too,” Ms. McNew said in email.

Both sites are located on the southern and southeastern coast of Santa Cruz Island, and feature the same scrubby arid habitat. Despite the habitat similarities between the rural and urban sites, there is one big difference: urban-dwelling finches dine on a banquet of human foods that are new to them whereas their rural-living cousins do not (ref). And it is well-known that, historically, food is the main driver of beak size and shape in Darwin’s finches.

Ms. McNew and her team captured more than 1,000 individuals of two Darwin’s finch species, the medium ground finch, Geospiza fortis, and the small ground finch, G. fuliginosa. Age and sex were identified for each bird based on size and plumage characters, and the team measured a variety of physical characteristics, including: beak depth, width, and length; leg (tarsus) length; wing length (wing chord); and body mass. A small blood sample was collected from each finch, and a sperm sample was collected from each male. Prior to release, each bird was marked with an uniquely numbered leg-band so individuals could be tracked.

The morphological measurements revealed that medium ground finches from urban areas were larger than their rural-dwelling relatives.

“We were very surprised to see that there was morphological differences between sites for one species. These sites are fairly close to one another and urbanization, like I mentioned, only happened recently. So at least for G. fortis [medium ground finches], it seems like some environmental differences between our urban and rural sites (which are only 10km apart!) are leading to larger finches,” Ms. McNew said.

In contrast, there were no consistent differences between rural and urban populations of small ground finches. This is not surprising since previous work found that medium ground finches’ phenotypes are more variable than small ground finches’ on Santa Cruz Island, and thus, this discovery is consistent with previous findings that medium ground finches adapt more rapidly to local conditions than do small ground finches.

When genetic analyses were conducted later in the lab, the research team found few genetic mutations in the genes encoding these measured traits in rural and urban representatives of both species, and none of those mutations were consistent. Since recent work showed that changes in the copy number of genes is linked to rapid evolution in pepper moths (ref) and in primates (ref), Ms. McNew and her team looked to see whether differences in gene copy number may explain the measured differences between urban and rural populations of these two finch species. Once again, they uncovered no fixed differences in gene copy numbers between the urban and rural populations for either species.

“There’s been some evidence (*Please read my comments below the article*) that certain genetic markers underlie variation in beak size and shape, but overall Geospiza finches are very difficult to distinguish genetically,” Ms. McNew said. “Could there be another source of phenotypic variation?”

When the team looked at epigenetics, they found a significant number of differences between urban and rural finches of both species.

“In the finches that we studied, epigenetic alterations between the populations were dramatic, but minimal genetic changes where observed,” said the study’s senior author, biologist Michael Skinner, a professor at Washington State University. Professor Skinner’s lab conducted the genetic and epigenetic analyses for this study.

The team also found these epigenetic differences were species-specific: few were shared between medium and small ground finches, in spite of their close family ties. This suggests that medium and small ground finches are each responding rapidly and in their own unique ways to environmental changes at the urban site.

“We were very excited to see epigenetic variation between both species of finches and for both cell types we studied (sperm and blood),” Ms. McNew said. (Epigenetic changes in sperm probably are heritable, whereas those in blood probably are not.)

Many of these observed epigenetic changes were associated with genes involved in metabolism and in intercellular communications. Other epigenetic mutations were associated with genes related to beak size and shape. These changes make intuitive sense in view of the fact that the diet of urban finches is diverging away from that consumed by rural populations (ref).

“These species of finch have distinct diets which could explain the differences in methylation patterns as diet is known to influence epigenetics,” Professor Skinner said.

Did the researchers know what to expect from this study?

“Our group published a paper a couple years ago investigating epigenetic variation among species of Darwin’s finches [ref]. In that case we did find that methylation variation existed among species and increased the more distantly related they were,” Ms. McNew said. “But for populations, especially very close ones, we really didn’t know what to expect.”

Although the team discovered many epigenetic differences between urban and rural representatives for both species, they still don’t know for sure if these alterations somehow influence the observed differences between the urban and rural populations of medium ground finches.

“We’re trying to be cautious in our interpretation of what these methylation changes mean,” Ms. McNew said in email.

“In this study we found morphological changes in one species (G. fortis) but not the other (G. fuliginosa) and we found methylation differences in both species,” Ms. McNew pointed out. “We did some preliminary mapping of differentially methylated regions to see if they were associated with any particular genes, but they were largely scattered all through the genome. So while some [differentially methylated regions] were associated with genes associated with beak growth, more work is needed to really nail down the function of these changes.”

Recent research has shown that a wide variety of stressful environmental events can create epigenetic changes.

“Work by Mike Skinner and others has shown that environmental stressors (pollutants, diet, etc.) can change methylation patterns,” Ms. McNew explained in email. “This means that animals could potentially respond to changes in their environment through these DNA methylation changes and that this response could be more rapid than selection on standing genetic variation.”

“This is a novel mechanism which is not seriously considered in evolutionary biology at this time,” Professor Skinner added.

The field of epigenetics is just getting started, especially research into epigenetic variation in wild populations.

“We think it’s very interesting though that there is epigenetic variation on this small scale (i.e. between two geographically close populations), especially since we could not distinguish the populations genetically,” Ms. McNew said. She noted that this research is “a first step in understanding if epigenetic changes are involved in adaptation to changing environments.”

Unfortunately, Ms. McNew doesn’t have any immediate plans to follow up. But she did share some of her research ideas if the opportunity arises in the future to explore these findings further.

“Ideally I’d love to do the same study at another couple of sites so we can better understand if the methylation variation is accumulating randomly or linked to urbanization and study parents and offspring so we can learn more about the heritability of these patterns.”"

Summary and conclusions:

• Food is the main driver of beak size and shape in Darwin’s finches. In other words, diet type (seeds, insects, fruits, cactus etc.) drives the beak size and shape.
• Changes in beak morphology occur rapidly, just in a couple of generations.
• Genetically all finches are very similar but they might have very different phenotypes.
• No genetic mutations were associated with these rapid phenotypic changes. However, a few genetic mutations were observed.
• When the team looked at epigenetics, they found a significant number of differences between urban and rural finches of both species.
  

My comment: Epigenetic readers, writers and erasers make it possible for organisms to rapidly adapt to changing environment. This ecological adaptation is based on complex epigenetic mechanisms and factors. Epigenetic modifications have nothing to do with randomness and they never lead to any kind of evolution. Instead, epigenetic alterations result in subtle genetic erosion and loss of biological information.

*) Is there any evidence that certain genetic markers underlie variation in beak size and shape? No. There are claims that changes in ALX1 gene regulate the beak size and shape. Actually, the ALX1 is a transcription factor, protein that binds to methylated regions of the DNA to act as a transcriptional start site. Methylation profiles control the binding of ALX1 and also activity of transcription (enhancers).

How does a stem cell know what to become?

Mutant heart cells don't beat

https://www.colorado.edu/today/2020/07/07/how-does-stem-cell-know-what-become-study-shows-rna-plays-key-role

Excerpts: "Look deep inside our cells, and you’ll find that each has an identical genome –a complete set of genes that provides the instructions for our cells’ form and function.

But if each blueprint is identical, why does an eye cell look and act differently than a skin cell or brain cell? How does a stem cell – the raw material with which our organ and tissue cells are made – know what to become?

In a study published July 6 CU Boulder researchers come one step closer to answering that fundamental question, concluding that the molecular messenger RNA (ribonucleic acid) plays an indispensable role in cell differentiation, serving as a bridge between our genes and the so-called “epigenetic” machinery that turns them on and off.

When that bridge is missing or flawed, the researchers report in the journal Nature Genetics, a stem cell on the path to becoming a heart cell never learns how to beat.

The paper comes at a time when pharmaceutical companies are taking unprecedented interest in RNA. And, while the research is young, it could ultimately inform development of new RNA-targeted therapies, from cancer treatments to therapies for cardiac abnormalities.
“All genes are not expressed all the time in all cells. Instead, each tissue type has its own epigenetic program that determines which genes get turned on or off at any moment,” said co-senior author Thomas Cech, a Nobel laureate and distinguished professor of biochemistry. “We determined in great detail that RNA is a master regulator of this epigenetic silencing and that in the absence of RNA, this system cannot work. It is critical for life.”

Scientists have known for decades that while each cell has identical genes, cells in different organs and tissues express them differently. Epigenetics, or the machinery that switches genes on or off, makes this possible.

But just how that machinery works has remained unclear.

In 2006, John Rinn, now a professor of biochemistry at CU Boulder and co-senior-author on the new paper, proposed for the first time that RNA - the oft-overlooked sibling of DNA (deoxyribonucleic acid) – might be key.

In a landmark paper in Cell, Rinn showed that inside the nucleus, RNA attaches itself to a folded cluster of proteins called polycomb repressive complex (PRC2), which is believed to regulate gene expression. Numerous other studies have since found the same and added that different RNAs also bind to different protein complexes.

The hotly debated question: Does this actually matter in determining a cell’s fate?

No fewer than 502 papers have been published since. Some determined RNA is key in epigenetics; others dismissed its role as tangential at best.

So, in 2015, Yicheng Long, a biochemist and postdoctoral researcher in Cech’s lab, set out to ask the question again using the latest available tools. After a chance meeting in a breakroom at the BioFrontiers Institute where both their labs are housed, Long bumped into Taeyoung Hwang, a computational biologist in Rinn’s lab.

A unique partnership was born.

“We were able to use data science approaches and high-powered computing to understand molecular patterns and evaluate RNA’s role in a novel, quantitative way,” said Hwang, who along with Long is co-first-author on the new paper.

In the lab, the team then used a simple enzyme to remove all RNA in cells to understand whether the epigenetic machinery still found its way to DNA to silence genes. The answer was ‘no.’

For a third step, they used the gene-editing technology known as CRISPR to develop a line of stem cells destined to become human heart muscle cells but in which the protein complex, PRC2, was incapable of binding to RNA. In essence, the plane couldn’t connect with air-traffic control and lost its way, and the process fell apart.“RNA seemed to be playing the role of air traffic controller, guiding the plane – or protein complex – to the right spot on the DNA to land and silence genes,” said Long.

By day 7, the normal stem cells had begun to look and act like heart cells. But the mutant cells didn’t beat. Notably, when normal PRC2 was restored, they began to behave more normally.

“We can now say, unequivocally, that RNA is critical in this process of cell differentiation,” said Long.

Previous research has already shown that genetic mutations in humans that disrupt RNA’s ability to bind to these proteins boost risk of certain cancers and fetal heart abnormalities.
Ultimately, the researchers envision a day when RNA-targeted therapies could be used to address such problems.

“These findings will set a new scientific stage showing an inextricable link between epigeneticsand RNA biology,” said Rinn. “They could have broad implications for understanding, and addressing, human disease going forward.”"

Summary and conclusions:

• RNA molecules guide epigenetic machinery to silence or activate certain DNA strands that are needed for tissue specific cell differentiation.
• In the absence of RNA, this system cannot work. It's critical for life. Mutant cells don't beat.
• Mutations disrupt RNA's ability to bind to necessary proteins. Mutations destroy information and they never lead to any kind of evolution.
• Reading, silencing and activating DNA is controlled by epigenetic mechanisms and factors. DNA is passive information. It has no control over cellular mechanisms.

Mutant heart cells don't beat. How do evolutionists think that heart cells evolved by random mutations and selection?

Massive and extensive scientific research does not support the theory of evolution but creation

Each species has its own specific mitochondrial sequence and other members of the same species are identical or tightly similar

https://www.sciencecodex.com/far-special-humanitys-tiny-dna-differences-are-average-animal-kingdom-620943

Excerpts: "Researchers report important new insights into evolution following a study of mitochondrial DNA from about 5 million specimens covering about 100,000 animal species."

"In genetic diversity terms, Earth's 7.6 billion humans are anything but special in the animal kingdom. The tiny average genetic difference in mitochondrial sequences between any two individual people on the planet is about the same as the average genetic difference between a pair of the world's house sparrows, pigeons or robins. The typical difference within a species, including humans, is 0.1% or 1 in 1,000 of the "letters" that make up a DNA sequence.

Genetic variation - the average difference in mitochondria DNA between two individuals of the same species - does not increase with population size.

The mass of evidence supports the hypothesis that most species, be it a bird or a moth or a fish, like modern humans, arose recently and have not had time to develop a lot of genetic diversity. The 0.1% average genetic diversity within humanity today corresponds to the divergence of modern humans as a distinct species about 100,000 - 200,000 years ago - not very long in evolutionary terms. The same is likely true of over 90% of species on Earth today.
Genetically the world "is not a blurry place." Each species has its own specific mitochondrial sequence and other members of the same species are identical or tightly similar. The research shows that species are "islands in sequence space" with few intermediate "stepping stones" surviving the evolutionary process.

The new study, "Why should mitochondria define species?" (online at http://bit.ly/2LnPK1g) relies largely on the accumulation of more than 5 million mitochondrial barcodes from more than 100,000 animal species, assembled by scientists worldwide over the past 15 years in the open access GenBank database maintained by the US National Center for Biotechnology Information.

"Experts have interpreted low genetic variation among living humans as a result of our recent expansion from a small population in which a sequence from one mother became the ancestor for all modern human mitochondrial sequences," says Dr. Thaler.

"Our paper strengthens the argument that the low variation in the mitochondrial DNA of modern humans also explains the similar low variation found in over 90% of living animal species - we all likely originated by similar processes and most animal species are likely young."

"Is genetic diversity related to the size of the population?" asks Dr. Stoeckle. "The answer is no. The mitochondrial diversity within 7.6 billion humans or 500 million house sparrows or 100,000 sandpipers from around the world is about the same."

"Scholars have previously argued that 99% of all animal species that ever lived are now extinct. Our work suggests that most species of animals alive today are like humans, descendants of ancestors who emerged from small populations possibly with near-extinction events within the last few hundred thousand years."

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."

Summary and conclusions:

• The research is very extensive; scientists analyzed mitochondrial DNA from about 5 million specimens covering about 100,000 animal species.
• Species mean 'a group of species' = kind
• The typical difference within a species (kind) is 0.1% or 1 in 1,000 of the "letters" that make up a DNA sequence. This same pattern is true within humans too.
• Species (kinds) are "islands in sequence space" - Intermediates disappear.
• Darwin struggled to understand the absence of intermediates and his questions remain fruitful.
• Each species has its own specific mitochondrial sequence and other members of the same species (kind) are identical or tightly similar
• Most animals, like humans, come from a small population that has survived a major catastrophe.
• According to researchers, about 90% of world's organisms originated at the same time about 100,000 to 200,000 years ago.
  
  But please note that researchers have used theoretical mtDNA mutation clocks based on phylogenetic analyses. Observed mtDNA mutation rates are roughly twenty-fold higher than estimates derived from phylogenetic analyses. This leads to a conclusion that ~90% of world's organisms originated at the same time about 4500 - 10,000 years ago. This large and extensive study perfectly supports biblical creation and worldwide flood, organismal variation in kinds and mtDNA degradation. Just like DNA mutations, mtDNA mutations never result in any kind of evolution.

Shortest list ever: Evidence of organs/structures produced by evolution

Can evolution produce new organs or structures? Theorists have no scientific evidence.

https://creation.com/images/pdfs/tj/j19_2/j19_2_76-82.pdf

Excerpts: "Organs theorized to be developing but not yet useful (but which are hypothesized to become useful in later evolutionary development) are called ‘nascent organs’. Nascent organs must exist if Darwinian evolution is true, but Darwin expected them to be rare at any one time in history because they would supposedly soon be supplanted by more perfectly functional organs. A literature review shows that all extant human and animal organs are fully operative in healthy individuals. For this reason, almost all evolutionists have dropped the idea of nascent organs, and, instead, believe that all functional organs evolved from previously existing functional ones. However, functional organs require a minimum level of irreducible complexity, and therefore the need to originate as nascent organs. This is a problem for Darwinian evolution, since nascent organs do not appear to exist."

"Evolution is based on the idea that all organs developed from simpler ones; thus, once the original organ evolved, new and improved organs subsequently evolved from it. For an organ or structure to be selected by natural selection, it must first exist. The challenge Darwinists face is to find evidence of new organs evolving—such as a primitive protolung or heart. ‘Simpler’ hearts exist, but all are functional and designed to allow the specific organism to survive in its environment.1 A particular organ may be larger or more complex in one animal than in another, but that does not necessarily mean it is ‘more evolved’. The letter ‘T’, for example, is more complex than an ‘I’, but it is not better, only different; both letters are ‘perfect’ for the task for which they were designed (effective communication).

 

Organs theorized to be developing, but not yet useful (yet which are hypothesized to be useful in later evolutionary development) are called nascent organs. Darwin expected to find few nascent organs at any one time in the living world, arguing that they would soon be supplanted by their more perfect successors. He also expected them to be comparatively rare at any one time in history because they would be replaced by more functional organs that would persist for a long time if they conferred a clear survival advantage to the organism. Nevertheless, according to his theory, Darwin expected to find in the living world at least some organs in a ‘nascent condition, and progressing toward further development’. He also gave us some idea of what to look for, but noted that it often would be ‘difficult to distinguish between rudimentary (i.e. atrophied through disuse) and nascent organs’.

Nascent organs (and nascent carbohydrate, protein and lipid structures as well) not only were predicted by Darwinism, but many must have existed historically if evolutionism occurred—a logical expectation of evolution, since all organs and structures would have been at one time nascent. However, after a century and half of looking, researchers have not found evidence of a single nascent organ developing in any plant or animal because all known organs are currently functional. A 2005 search of the over 18 million journal articles in two scientific literature databases using the term ‘nascent organ’ revealed that not a single example of a nascent organ has been demonstrated or even postulated. Only five studies were located, all of which related to the normal development of embryos. This literature review, and the study of life in general, indicates that all extant human and animal organs are functional and fully developed in healthy animals. For this reason, almost all evolutionists have dropped the idea of nascent organs and, instead, believe that all functional organs evolved from previously existing functional organs, not nascent organs. A problem with this conclusion is explaining the source of completely new types of organs such as the liver or the special senses."

"A literature search has determined that no claimed examples of nascent organs or intermediate organs exist today. Consequently, it is widely recognized that Darwin’s theory of nascent organs has been disproved and replaced by a theory that postulates that all organs evolved from other simpler organs. This theory is also problematic in that organs must be of a certain complexity before they can function, a concept called ‘irreducible complexity’. Nascent organs are therefore still required in Darwinian theory but they do not appear to exist. (By Jerry Bergman) "

My comment: Why to maintain a theory that has no evidence?

Active epigenetic modifications are also passed from one generation to the next

Parents pass on much more than just genes to their offspring - This is how the 'survival of the fittest' works

https://www.sciencedaily.com/releases/2020/06/200604152046.htm

Excerpt: "Parents pass genes along to their offspring which equip them for their future life. In recent years, research has shown that the reality is much more complex and that parents endow much more than just genes. A new study reveals that active epigenetic modifications are also passed from one generation to the next.

We inherit genetic information from our parents encoded in the DNA sequence. However, even though all cells in the human body contain the same DNA, they "express" different genes to fulfill different functions. DNA is wrapped around histone proteins forming a single repeating unit called the nucleosome. Many nucleosomes join together to form the "chromatin" located in the nucleus of all cells.

Epigenetic modifications such as the addition of chemical groups to histones lead to changes in chromatin organization, which can trigger either gene activation ("expression") or gene silencing. Epigenetics thereby represents an additional layer of information that helps cells to determine which genes to activate. Despite their common genome, cells in our body therefore possess different "epigenomes." 

The parent's germ cells, the oocyte and the sperm, fuse to make a new organism during fertilization. It is thought that most epigenetic marks are erased between each generation. This epigenetic reset allows all genes to be read afresh for each new individual. Now, scientists from the laboratory of Asifa Akhtar discovered that one particular histone modification, the acetylation of histone H4 on the 16th lysine (H4K16ac in short) is intergenerationally maintained from the mother's oocyte to the young embryo.

"H4K16ac is an epigenetic modification that is typically associated with the activation of genes. However, we know that genes are not expressed in either the oocyte or in the first 3 hours of the embryo's life. This begs the question: what is H4K16ac doing at this early stage?" says Asifa Akhtar. To investigate the function of this histone mark in early fly development, the team performed a panel of genome-wide analyses. They found that numerous DNA regions were "marked" by H4K16ac during the early developmental stages before the onset of their gene activation.

The importance of H4K16ac for the offspring became apparent when the mother failed to transmit this mark to her children. The scientists designed experiments using genetic approaches and transgenic flies to remove the enzyme MOF from fly mothers. MOF is known to be responsible for the deposition of the H4K16ac modification.

Remarkably, when the scientists studied the offspring that were laid without the H4K16ac information, they found that genes marked by H4K16ac under normal conditions were now no longer appropriately expressed, and their chromatin organization was severely disrupted. The majority of embryos which failed to get the maternal H4K16ac instructions subsequently died from catastrophic developmental defects. "H4K16ac has an instructive function in the germline and is indispensable for embryonic development later on. It is almost like the mother leaves sticky notes with instructions on where to find the food or who to call in an emergency and so on, when the child is home alone for the first time," says Maria Samata, the first author of the study."

My comment: This discovery pinpoints the importance of epigenetic inheritance in all kinds of organisms. Because DNA is just passive information that doesn't determine organismal traits and characteristics, it's necessary for working inheritance to pass on epigenetic information to the offspring. Mechanisms for this trans- and intergenerational memory transfer are already partly understood and I've written about them in here, here, here and here. The so called 'survival of the fittest' is based on this epigenetic memory transfer and it never results in any kind of evolution. Don't be deceived, my friends.

After 100 years of human engineering, the best man-made electric motor doesn't beat bacterial motors

Bacterial flagellar motor operates at close to 100% efficiency

https://new.abb.com/news/detail/1789/ABB-motor-sets-world-record-in-energy-efficiency-saves-half-a-million-dollars

Excerpt: "Tests carried out on a 44 megawatt 6-pole synchronous ABB motor shortly before delivery showed an efficiency 0.25 percent greater than the 98.8 percent stipulated in the contract, resulting in the world record for electric motor efficiency. This efficiency improvement could save approximately $500,000 in electrical energy costs over the course of a 20-year lifetime for each motor."

                                                         Synchronous motor electrical design

https://www.tandfonline.com/doi/full/10.1080/23746149.2017.1289120

Excerpt: "This interaction is powered by the ion-motive force arising from the transit of ions (protons, in the case of the commonly studied Escherichia coli motor) across the cellular membrane. The BFM is remarkable in its ability to efficiently convert the free energy stored in this transmembrane electrochemical gradient into mechanical work: while man-made engines lose significant amounts of energy to heating, the BFM operates at close to 100% efficiency. Rotating at approximately 300 Hz (or 18000 rpm; compare to the upper limit of a typical car engine’s rotational speed of 6000 rpm), the E. coli motor can output a power of approximately 1.5 x 10^5 pN nm s-1 and propel the bacteria at a speed up to 100 um s-1 – that is, up to 100 body lengths per second! The BFM of other species have been shown to rotate several times faster."

                                                                     Bacterial motor electrical design

My comment: The bacterial flagellar motor is one of the most powerful and efficient machines in existence. MO-1 marine bacterium has seven this kind of super-efficient ion flow motors synchronized with a 24-gear planetary gearbox to produce maximum power and torque. Evolution or Design? Man-made motors, after a hundred years of development, still don't beat these design masterpieces. And what's more astonishing is that bacteria are able to reproduce and clone these mechanical nano motors.

How can different cells do so many different things even when they all have the same DNA?

Mechanisms behind cellular differentiation are the same as why organisms change in nature - Epigenetics

https://onlinelibrary.wiley.com/doi/10.1111/apa.15050

Excerpts: "All our cells contain more or less identical deoxyribonucleic acid (DNA). Yet they constitute organs each with specific tasks and roles in our body. The genome in every cell is the same, but the epigenome is different and this contributes to differences in protein expression."

"The epigenome refers to all epigenetic marks on the genome, in other words the overall epigenetic state or functional genome of the cell. Epigenetics, which literally means on top of genetics, is defined as the mechanisms of heritable, over cell divisions, specific cell functions or phenotypes that do not directly involve the primary DNA sequence. Epigenetic mechanisms enable the environment to interact with genes, switching them on and off, and this regulates the plasticity of the cell phenotype. This functional genome with DNA transcription and ribonucleic acid (RNA) translation is responsible for the protein expression in each cell and, ultimately, the phenotype."

                     During butterfly metamorphosis the DNA is the same in all four stages but epigenome is different.

"Epigenetics is a dynamic process in cell differentiation that was first described by Waddington in the 1950s. He depicted an epigenetic landscape and described epigenetics as the branch of biology that studies the causal interactions between genes and their products, which brings the phenotype into being. Epigenetic marks change, and make changes, as cells differentiate and this process can persist through mitosis and meiosis as cells divide."

"The modern definition of epigenetics refers to a modification that is not a mutation and that is initiated by a signal. It is inherited during mitosis, even in the absence of this signal, and that affects the regulation of gene transcription and ultimately protein translation. Mechanisms can be pre‐ or post‐translational, such as DNA methylation and histone modification, respectively. Epigenetic modifications change the accessibility of DNA for transcription to RNA in different ways. The most studied epigenetic mechanism is DNA methylation, as methylation is stable, DNA is easy to extract from cells and possible to store."

A few examples of epigenetic regulation and how it affects the phenotype:

A soldier or a worker ant? This is regulated by epigenetic mechanisms and factors. No mutations, no selection.

Diet of royal jelly during larval development generates queen bees. The DNA is the same as in workers.

Darwin's finches are different due to changes in diet types. Nothing to do with random mutations and evolution. This is ecological adaptation and epigenetic regulation.

The new study shows that epigenetic-based silencing of a large set of genes limits the eye development of cave-dwelling A. mexicanus fish. 

My comment: Ecological adaptation, organismal change, phenotypic change and variation are always based on epigenetic regulation of pre-existing biological information. Epigenetic modifications, however, often result in minor errors in underlying DNA. This makes genomes weaker mostly due to tendency of GC-content turning to AT-content. Consequences are observable; weakening immune systems, smaller organisms, extinction etc. Nothing is evolving on this planet. Don't get lost, my friends.