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.

Lack of transitional forms - still the major problem with the evolutionary theory

Darwin struggled to understand the absence of intermediates and his questions remain fruitful

https://scientificinquirer.com/2018/06/07/humans-are-about-as-genetically-diverse-as-any-other-animal/

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

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

“The research is a new way to show that species are ‘islands in sequence space.’ Each species has its own narrow, very specific consensus sequence, just as our phone system has short, unique numeric codes to tell cities and countries apart.”
Adds Dr. Thaler: “If individuals are stars, then species are galaxies. They are compact clusters in the vastness of empty sequence space.” "

Professionals expose the problems with Darwin's theory:

D.S. WOODROFF, Univ. of CA, San Diego: "But fossil species remain unchanged throughout most of their history and the record fails to contain a single example of a significant transition."< Science>, Vol.208, 1980, p.716

David M. Raup, Curator of Geology, Field Museum of Natural History, Chicago: "Darwin... was embarrassed by the fossil record... we are now about 120-years after Darwin and the knowledge of the fossil record has been greatly expanded. We now have a quarter of a million fossil species but the situation hasn't changed much. The record of evolution is still surprisingly jerky and, ironically, ... some of the classic cases of Darwinian change in the fossil record, such as the evolution of the horse in North America, have had to be discarded or modified as a result of more detailed information." "Conflicts Between Darwin and Paleontology" Field Museum of Natural History Vol. 50, No. 1, (Jan, 1979), p. 25

ORDERS, CLASSES, & PHYLA , GEORGE GAYLORD SIMPSON, Harvard: "Gaps among known species are sporadic and often small. Gaps among known orders, classes, and phyla are systematic and almost always large.", , p. 149

ARBITRARY ARRANGEMENT , R.H. DOTT, U. of Wis. & R.L. BATTEN, Columbia U., A.M.N.H.: "We have arranged the groups in a traditional way with the 'simplest' forms first, and progressively more complex groups following. This particular arrangement is arbitrary and depends on what definition of 'complexity' you wish to choose. ...things are alike because they are related, and the less they look alike, the further removed they are from their common ancestor." , p.602

SEPARATE LIVING KINDS , STEPHEN JAY GOULD, Harvard: "Our modern phyla represent designs of great distinctness, yet our diverse world contains nothing in between sponges, corals, insects, snails, sea urchins, and fishes (to choose standard representatives of the most prominent phyla).", , p.15, Oct. 1990

FOSSILS INDICATE CREATION! E.J.H. CORNOR, Cambridge: "Much evidence can be adduced in favor of the Theory of Evolution from Biology, Biogeography, and Paleontology, but I still think that to the unprejudiced the fossil record of plants is in favor of special creation." , p.61

"TREES" NOT FROM FOSSILS , S. J. GOULD, Harvard: "The evolutionary trees that adorn our textbooks have data only at the tips and nodes of their branches; the rest is inference, however reasonable, not the evidence of the fossils.", ., V.86, p.13

STORY TIME , COLIN PATTERSON, Senior Paleontologist, British Museum of Nat. History: "You say I should at least 'show a photo of the fossil from which each type or organism was derived.' I will lay it on the line-there is not one such fossil for which one could make a watertight argument." "It is easy enough to make up stories of how one form gave rise to another. ... But such stories are not part of science, for there is no way of putting them to the test. ... I don't think we shall ever have any access to any form of tree which we can call factual."< HARPER'S>, Feb. 1984, p.56

Darwin's Enigma: Fossils and Other Problems, 4th edition, Master Books, Luther D. Sunderland: "Now, after over 120 years of the most extensive and painstaking geological exploration of every continent and ocean bottom, the picture is infinitely more vivid and complete than it was in 1859. Formations have been discovered containing hundreds of billions of fossils and our museums are filled with over 100-million fossils of 250,000 different species. The availability of this profusion of hard scientific data should permit objective investigators to determine if Darwin was on the right track. What is the picture which the fossils have given us? ... The gaps between major groups of organisms have been growing even wide and more undeniable. They can no longer be ignored or rationalized away with appeals to imperfection of the fossil record."  1988, p. 9

Random mutations never result in evolution

30 years ago: Mutation driven evolution - Today: Clever and complex mechanisms such as RNA editing

Modern science has revealed several incredible mechanisms behind cellular differentiation and organismal adaptation. One of the most sophisticated mechanisms by which the cell is able to increase the number of different proteins without the need to increase the number of genes (DNA) in the genome, is RNA editing. Together with alternative splicing, these two mechanisms make it possible for the cell to produce a huge number of different proteins without modifying the underlying DNA. But 20-30 years ago these mechanisms were not well understood in scientific research and this is why many people are indoctrinated with a pseudoscientific mantra: 'mutation driven evolution'. However, newest research has found out many complex mechanisms that require Intelligent Design. Let's have an example: Apolipoprotein B-100.

https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Biology_(Kimball)/06%3A_Gene_Expression/6.05%3A_RNA_Editing

 

Humans have a single locus encoding the APOB gene.

• It contains 29 exons (separated by 28 introns).
• The exons contain a total of 4564 codons.
• Codon 2153 is CAA, which is a codon for the amino acid glutamine (Gln).
• The gene is expressed in cells of both the liver and the intestine.
• In both locations, transcription produces a pre-messenger RNA that must be spliced to produce the mRNA to be translated into protein.
• In the Liver. Here the process occurs normally producing apolipoprotein B-100 — a protein containing 4,563 amino acids — that is essential for the transport of cholesterol and other lipids in the blood.
• In the Intestine
  • In the cells of the intestine, an additional step of pre-mRNA processing occurs: the chemical modification of the C nucleotide in Codon 2153 (CAA) into a U.
  • This RNA editing changes the codon from one encoding the amino acid glutamine (Gln) to a STOP codon (UAA)
  • The modification is catalyzed by the enzyme cytidine deaminase that
    • recognizes the sequence of the RNA at that one place in the molecule and
    • catalyzes the deamination of C thus forming U.
  • Translation of the mRNA stops at codon #2153 forming apolipoprotein B-48 — a protein containing 2152 amino acids — that aids in the absorption of dietary lipids from the contents of the intestine.

My comment: This clever modification was done by a cytidine deaminase that converts a C in the RNA to uracil (U). Another, even more sophisticated substitutional RNA editing mechanism is A-to-I RNA editing. This is a masquearading technique; a mechanism that converts adenosine residues to inosine residues (which masquerade as guanosine residues) in messenger RNA. The cell is also able to insert/delete/repair nucleotides in the RNA (mediated by guide RNAs). Both alternative splicing and RNA editing mechanisms are controlled by epigenetic mechanisms and factors. They help us understand that rich biodiversity is based on clever mechanisms, not random mutations and selection. We can observe change in created kinds which is not evolution. Don't get lost, my friends.

Speciation is not evolution - Epigenetic mechanisms behind organismal change

Speciation can occur rapidly and there's no need for a single change in DNA

https://news.mit.edu/2012/rna-splicing-species-difference-1220

Excerpts:"When genes were first discovered, the canonical view was that each gene encodes a unique protein. However, biologists later found that segments of genes can be combined in different ways, giving rise to many different proteins.
This phenomenon, known as alternative RNA splicing, often alters the outputs of signaling networks in different tissues and may contribute disproportionately to differences between species, according to a new study from MIT biologists.

After analyzing vast amounts of genetic data, the researchers found that the same genes are expressed in the same tissue types, such as liver or heart, across mammalian species. However, alternative splicing patterns — which determine the segments of those genes included or excluded — vary from species to species."

"Alternative RNA splicing (a discovery for which MIT Institute Professor Phillip Sharp shared the 1993 Nobel Prize in medicine or physiology), controls the composition of proteins encoded by a gene. In mammals, genes — made of DNA stored in the cell nucleus — consist of many short segments known as exons and introns. After the DNA is copied into an RNA transcript, all introns and frequently some exons are excised before the messenger RNA (mRNA) leaves the nucleus, carrying instructions to make a specific protein.

This process allows cells to create a much wider variety of proteins than would be possible if each gene encoded only one protein. Some proteins, including Dscam in fruit flies and neurexin in humans, have thousands of alternate forms. These variant proteins can have vastly different functions, Burge says."

"Because splicing patterns are more specific to each species, it appears that splicing may contribute preferentially to differences between those species, Burge says. “Splicing seems to be more malleable over shorter evolutionary timescales, and may contribute to making species different from one another and helping them adapt in various ways,” he says.

The new study is the first large-scale effort to look at the role of alternative splicing in evolution, says Brenton Graveley, a professor of genetics and developmental biology at the University of Connecticut Health Center. “It provides a lot of new insight into the potential role of alternative splicing in driving differences between species,” says Graveley, who was not involved in this study."

My comment: Alternative RNA splicing is regulated by epigenetic factors and mechanisms, such as DNA methylation profiles, histone epigenetic markers and non coding RNA molecules. Alternative splicing (AS) makes it possible to have alternate forms (The Bible: 'After its kind') from the same organism. This might happen in adaptational events. During and after the AS procedure, NO NEW information is generated, but pre-existing information is regulated, shuffled and re-used along the adaptational needs. Alternative splicing is a basic mechanism in both prokaryotes and eukaryotes. In humans, the AS works like a masterpiece; our cells can produce millions of different proteins just by reading ~19,000 strands of DNA. This kind of use of DNA also points out that DNA is just a passive data base. Evolution never happened. Don't get lost.

Keywords: alternative splicing speciation, alternative splicing phenotypic novelty