https://www.sciencedaily.com/releases/2023/01/230124101607.htm

"The cells of humans and all other higher organisms use a complex system of checkpoints and "licensing" proteins to ensure that they replicate their genomes precisely once before dividing. In preparation for cell division, the licensing proteins attach to specific regions in the DNA, designating them as replication origins. When the DNA synthesis phase of the cell cycle begins, replication begins only at those licensed sites, and only initiates, or "fires" once, according to the current model.

"That model was missing a crucial point, though. "The same factor that is allowing for this licensing to happen is only degraded after these replication origins have fired," said senior author Dr. Tobias Meyer, the Joseph Hinsey Professor in Cell and Developmental Biology at Weill Cornell Medicine. "In principle, the cell could load these licensing machines onto DNA that's already replicated, so, instead of two copies, you're getting three or four copies of that segment of the DNA, and these cells would be expected to lose genome integrity and die or become cancerous."

***

"The work revealed that a well-known licensing factor, CDT1, not only licenses a segment of DNA to become a replication origin, but also acts as a brake for DNA replication, preventing an essential replication enzyme called CMG helicase from functioning. To start synthesizing DNA, the cell's enzymes must first break down CDT1. "Previously proposed mechanisms for coordinating this transition from the licensing phase of the cell cycle to the firing phase of the cell cycle have depended on inhibiting licensing factors," said Ratnayeke, adding that "the mechanism that we identified here is actually the opposite … the licensing factor CDT1 itself is preventing the progression of DNA synthesis."

"To confirm their results, the scientists collaborated with colleagues at the Medical Research Council in Cambridge, UK, who found that the inhibitory mechanism can be recapitulated in a simplified system that reproduces the entire DNA synthesis process with purified components in a test tube. "That allowed us to reconstitute all the components for DNA synthesis, and to prove that CMG helicase is directly inhibited by CDT1," said Dr. Meyer, who is also a professor of biochemistry and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine."

Comment: another obviously deigned system requiring specific giant enzymes in place.

https://www.the-scientist.com/news-opinion/mammalian-oocytes-store-mrna-in-newly-found-...

"During the final stages of oocyte growth, these germ cells become transcriptionally inactive while preparing to resume meiosis and jumpstart their maturation into eggs. At this austere time, oocytes can only use maternal messenger RNAs (mRNAs) they have previously stored to get through their maturation process and early embryonic development if fertilized. Oocytes from the worm Caenorhabditis elegans store mRNA in P granules, those of fruit flies do so in polar granules, and aquatic frogs and zebrafish rely on a structure called the Balbiani body—all of which are membraneless organelles. But for mammals, the storage site has been terra incognita so far.

***

"A study published online today (October 20) in Science sheds light on the enigma, showing that these oocytes accumulate mRNA in a membraneless compartment that is associated with mitochondria. The study’s authors report that they observed this newly discovered structure in various mammalian species, including mice and humans.

***

"To answer it, he and his colleagues first used various staining techniques to establish that both RNA-binding proteins and mRNA are colocalized with mitochondria in mouse, pig, cow, and human oocytes. These molecules cluster around mitochondria throughout the cytoplasm, forming a structure the team named the mitochondria-associated ribonucleoprotein domain (MARDO). They observed that MARDO becomes more prominent as oocytes grow larger, and that its formation is dependent on the parallel increase in mitochondrial membrane potential.

"Cheng and his colleagues further showed that the RNA-binding protein ZAR1, which had been previously associated with oocyte maturation and mRNA regulation, plays an essential role in both MARDO assembly and dissolution in mouse oocytes. In the team’s experiments, ZAR1 promoted MARDO coalescence and its association with mitochondria. Once the oocyte transforms into a fertilized egg and the embryo starts to grow, transcription is restored and maternal mRNAs are no longer needed to drive embryonic development. During this transition, the team found that ZAR1 is degraded by the proteosome, and with that, MARDO is dissolved."

Comment: the mRNAs contain the information to control preparations for fusion with the male sperm.

https://www.sciencedaily.com/releases/2022/10/221021145842.htm

"Butterfly wing patterns have a basic plan to them, which is manipulated by non-coding regulatory DNA to create the diversity of wings seen in different species, according to new research.

"The study, "Deep cis-regulatory homology of the butterfly wing pattern ground plan," published as the cover story in the Oct. 21 issue of Science, explains how DNA that sits between genes -- called 'junk' DNA or non-coding regulatory DNA -- accommodates a basic plan conserved over tens to hundreds of millions of years while at the same time allowing wing patterns to evolve extremely quickly.

"The research supports the idea that an ancient color pattern ground plan is already encoded in the genome and that non-coding regulatory DNA works like switches to turn up some patterns and turn down others.

***

"/We see that there's a very conserved group of switches [non-coding DNA] that are working in different positions and are activated and driving the gene," Mazo-Vargas said.

***

"This study focused on the effect of non-coding DNA on the WntA gene. Specifically, the researchers ran experiments on 46 of these non-coding elements in five species of nymphalid butterflies, which is the largest family of butterflies.

***

"The researchers found that across four of the species -- Junonia coenia (buckeye), Vanessa cardui (painted lady), Heliconius himera and Agraulis vanillae (gulf fritillary) -- each of these non-coding elements had similar functions with respect to the WntA gene, proving they were ancient and conserved, likely originating in a distant common ancestor.

"They also found that D. plexippus (monarch) used different regulatory elements from the other four species to control its WntA gene, perhaps because it lost some of its genetic information over its history and had to reinvent its own regulatory system to develop its unique color patterns.

"'We have progressively come to understand that most evolution occurs because of mutations in these non-coding regions," Reed said."

Comment: repeating the same successful plan over and over makes perfect sense. Reed's comment is right on point. To make a new species genes must be re-regulated to produce a new form.

https://wis-wander.weizmann.ac.il/chemistry/calling-through-dna-wire

"Proteins can communicate through DNA, conducting a long-distance dialogue that serves as a kind of genetic “switch,” according to Weizmann Institute of Science researchers. They found that the binding of proteins to one site of a DNA molecule can physically affect another binding site at a distant location, and that this “peer effect” activates certain genes. This effect had previously been observed in artificial systems, but the Weizmann study is the first to show it takes place in the DNA of living organisms.

"A team headed by Dr. Hagen Hofmann of the Chemical and Structural Biology Department made this discovery while studying a peculiar phenomenon in the soil bacteria Bacillus subtilis. A small minority of these bacteria demonstrate a unique skill: an ability to enrich their genomes by taking up bacterial gene segments scattered in the soil around them. This ability depends on a protein called ComK, a transcription factor, which binds to the DNA to activate the genes that make the scavenging possible. However, it was unknown how exactly this activation works.

***

"They found that when two ComK molecules bind to one of the sites, it sets off a signal that facilitates the binding of two additional ComK molecules at the second site. The signal can travel between the sites because physical changes triggered by the original proteins’ binding create tension that is transmitted along the DNA, something like twisting a rope from one end. Once all four molecules are bound to the DNA, a threshold is passed, switching on the bacterium’s gene scavenging ability.

“'We were surprised to discover that DNA, in addition to containing the genetic code, acts like a communication cable, transmitting information over a relatively long distance from one protein binding site to another,” Rosenblum says.

"By manipulating the bacterial DNA and monitoring the effects of these manipulations, the scientists clarified the details of the long-distance communication within the DNA. They found that for communication – or cooperation – between two sites to occur, these sites must be located at a particular distance from one another, and they must face the same direction on the DNA helix. Any deviation from these two conditions – for example, increasing the distance – weakened the communication. The sequence of genetic letters running between the two sites was found to have little effect on this communication, whereas a break in the DNA interrupted it completely, providing further evidence that this communication occurs through a physical connection.

“'Long-distance communication within a DNA molecule is a new type of regulatory mechanism – one that opens up previously unavailable methods for designing the genetic circuits of the future,” Hofmann says."

Comment: More magic in DNA, an amazing molecule with all sorts of hidden designed functions. Not by chance mutations

https://www.newscientist.com/article/2294549-female-african-elephants-evolved-to-lose-t...

"Female elephants in Mozambique rapidly evolved to become tuskless as a result of intense ivory poaching during the country’s civil war, even though one of the mutations involved kills male offspring.

"During the war, from 1977 to 1992, both sides hunted elephants for ivory, and the elephant population of Gorongosa National Park plummeted. Now an analysis of historical video footage and contemporary sightings by Shane Campbell-Staton at Princeton University and his colleagues has shown that the proportion of tuskless females rose from 19 to 51 per cent during the conflict, and a statistical analysis indicated this was extremely unlikely to have occurred in the absence of a selective pressure. The proportion of tuskless elephants has been declining since the war ended.

"This loss of tusks due to ivory hunting or poaching has happened in many other places too. For instance, in Sri Lanka less than 5 per cent of male Asian elephants still have tusks.

"Oddly, though, all male African elephants have retained their tusks despite the pressure of hunting. This appears to be the result of a genetic quirk.

"The team hasn’t yet found the precise genetic changes that cause tusklessness in females, but it appears two mutations are involved. One is probably in a gene on the X chromosome called AMELX, which plays a part in tooth formation.

"It appears this mutation also affects other, crucial genes nearby. Females have two copies of the X chromosome, so if one copy isn’t mutated, the genes it carries will still function normally and the elephant will still be healthy. But males have only one X chromosome, so this mutation is lethal to any males that inherit it.

"Much the same genetic condition can occur in people, says Campbell-Staton. Women with it lack upper lateral incisors – the equivalent of tusks – and male fetuses that inherit the mutation are usually lost in the third trimester."

Comment: Cutting off rat tails by August Weismann supposedly killed Lamarck's theory, so why is the same sort of event working now?

https://www.science.org/doi/full/10.1126/science.abj6856?af=R

"Abstract
IscB proteins are putative nucleases encoded in a distinct family of IS200/IS605 transposons and are likely ancestors of the RNA-guided endonuclease Cas9, but the functions of IscB and its interactions with any RNA remain uncharacterized. Using evolutionary analysis, RNA sequencing, and biochemical experiments, we reconstructed the evolution of CRISPR-Cas9 systems from IS200/IS605 transposons. We found that IscB uses a single noncoding RNA for RNA-guided cleavage of double-stranded DNA and can be harnessed for genome editing in human cells. We also demonstrate the RNA-guided nuclease activity of TnpB, another IS200/IS605 transposon-encoded protein and the likely ancestor of Cas12 endonucleases. This work reveals a widespread class of transposon-encoded RNA-guided nucleases, which we name OMEGA (obligate mobile element–guided activity), with strong potential for developing as biotechnologies.

***

"Discussion
Naturally programmable biological systems offer an efficient solution for diverse organisms to achieve scalable complexity via modularity of their components. RNA-guided defense and regulatory systems, which are widespread in prokaryotes and eukaryotes, are a prominent case in point, and have served as the basis of numerous biotechnology applications thanks to the ease with which they can be engineered and reprogrammed.

Here, through the exploration of Cas9 evolution, we discovered the programmable RNA-guided mechanism of three highly abundant but previously uncharacterized transposon-encoded nucleases: IscB, IsrB, and TnpB, which we collectively refer to as OMEGA (obligate mobile element–guided activity) because the mobile element localization and movement likely determines the identity of their guides. Although the biological functions of OMEGA systems remain unknown, several hypotheses are compatible with the available evidence, including roles in facilitating TnpA-catalyzed, RNA-guided transposition, or acting as a toxin, with the transposon acting as the antitoxin, securing maintenance of IS200/IS605 insertions."

Comment: This highly complex mechanism is not fully understood as yet. But it is obviously irreducibly complex and was designed at the initiation of DNA coding. Chance cannot produce this.

https://www.quantamagazine.org/scientists-catch-jumping-genes-rewiring-genomes-20210512/

"For more than a decade, Feschotte has pointed to transposons as the ultimate innovators in eukaryotic genomes. Transposons are genetic elements that can copy themselves and insert those copies throughout the genome using a splicing enzyme they make. Feschotte may have finally found the smoking gun he has been looking for: As he and his colleagues recently reported in Science, these jumping genes have fused with other genes nearly 100 times in tetrapods over the past 300 million years, and many of the resulting genetic mashups are likely to encode transcription factors.

"David Adelson, chair of bioinformatics and computational genetics at the University of Adelaide in Australia, who was not involved with the study, said, “This study provides a good mechanistic understanding of how these new genes can form, and it squarely implicates the transposon activity itself as the cause.”

"Scientists have long known that transposons can fuse with established genes because they have seen the unique genetic signatures of transposons in a handful of them, but the precise mechanism behind these unlikely fusion events has largely been unknown. By analyzing genes with transposon signatures from nearly 600 tetrapods, the researchers found 106 distinct genes that may have fused with a transposon. The human genome carries 44 genes likely to have been born this way.

"The structure of genes in eukaryotes is complicated, because their blueprints for making proteins are broken up by introns. These noncoding sequences are transcribed, but they get snipped out of the messenger RNA transcripts before translation into protein occurs. But according to Feschotte’s new study, a transposon can occasionally hop into an intron and change what gets translated. In some of these cases, the protein made by the fusion gene is a mashup of the original product and the transposon’s splicing enzyme (transposase).

***

"Cosby described the 106 fusion genes described in the study as the “tiniest tip of the iceberg.” Adelson agreed and explained why: Events that randomly create fusion genes for functional, non-harmful proteins rely on a series of coincidences and must be exceedingly rare; for the fusion genes to spread throughout a population and withstand the test of time, nature must also positively select for them in some way. For the researchers to have found the examples described in the study so readily, transposons must surely cause fusion events much more often, he said.

***

"Transposons comprise a hefty chunk of eukaryotic DNA, yet organisms take extreme measures to carefully regulate their activity and prevent the havoc caused by problems such as genomic instability and harmful mutations. These dangers made Adelson wonder if fusion genes sometimes endanger orderly gene regulation. “Not only are you perturbing one thing, but you’re perturbing this whole cascade of things,” he said. “How is it that you can change expression of all these things and not have a three-headed bat?” Cosby, however, thinks it’s unlikely that a fusion gene leading to harmful morphogenic changes would readily propagate through a population.

"Damon Lisch, a plant geneticist at Purdue University who studies transposable elements and was not involved with the study, said he hopes this study pushes back against a widespread but misguided notion that transposons are “junk DNA.” Transposable elements generate tremendous amounts of diversity and have been implicated in the evolution of the placenta and the adaptive immune system, he explained. “These are not junk — they’re living little creatures in your genome that are under very active selection over long periods of time, and what that means is that they evolve new functions to stay in your genome,” he said.

"Though this study highlights the mechanism underlying transposase fusion genes, the vast majority of new genetic material is thought to form through genetic duplication, in which genes are accidentally copied and the extras diverge through mutation. But a large quantity of genetic material does not mean that new protein functions will be significant, said Cosby, who is continuing to investigate the function of the fusion proteins.

“'Evolution is the ultimate tinkerer and ultimate opportunist,” said David Schatz, a molecular geneticist at Yale University who was not involved with the study. “If you give evolution a tool, it may not use it right away, but sooner or later it will take advantage of it.'” (my bold)

Comment: The last paragraph treats evolution as if if is a personage. Why not simply God in action?

https://www.sciencenews.org/article/archaea-microbes-fold-twist-contort-dna-extreme-ways

"Single-celled archaea microbes pack their DNA into flexible coils that expand and stretch much like a Slinky does. This kind of molecular gymnastics had never been seen before in other organisms and may represent a way for archaea to get easy access to their genetic material, researchers report March 2 in eLife.

***

“'You would think that this would really contort the DNA in an awful shape, but it actually flows very naturally.”

***

"In 2017, Luger and her colleagues discovered that archaea — microbes that resemble bacteria under the microscope but are quite distinct — can spool their DNA around small proteins called histones (SN: 8/10/17). This process is strikingly similar to how plants, animals and fungi bend and fold their own genomes into compact, disk-shaped units known as nucleosomes.

"But nobody knew what these structures looked like in archaea, or how the microbes gained access to their spooled DNA. Using computer simulations and electron microscopy experiments on the genetic material of Methanothermus fervidus, a heat-loving archaeal species, the researchers found the Slinky-like shapes opened and closed in a clamshell motion.

“'My gut reaction was: ‘Wow! So pretty!’” says Luger. “My second reaction was: ‘Of course! This makes so much sense!’”

"Complex organisms such as humans, palm trees or mushrooms depend on a sophisticated machinery to loosen their highly compacted nucleosomes and gain access to specific genes. Archaea microbes might instead simply be contorting their DNA to turn genes on and off –– allowing proteins to “read” the genes when the Slinkies open, and cutting off access when they close."

Comment: Archaea are our oldest ancestors. This means complex DNA code reading came with or shortly after the appearance of life.

https://phys.org/news/2021-03-genes-sex-chromosomes.html

"Because human females have two X chromosomes and males have one X and one Y, somatic cells have special mechanisms that keep expression levels of genes on the X chromosome the same between both sexes. This process is called dosage compensation and has been extensively studied in the fruit fly Drosophila. Now, researchers at the University of Tsukuba (UT) continued work with Drosophila to show that dosage compensation does not occur in the germ cells of male flies.

"In an article published in Scientific Reports, the UT researchers investigated this phenomenon in fly primordial germ cells (PGCs), which are present in embryos and are the precursor cells to what ultimately become sperm and eggs in adults. Previous reports on dosage compensation in this cell type were controversial.

"Genetic research in somatic cells has shown that expression of X-linked genes in male fruit flies is upregulated to reach equivalent levels to that of their female counterparts. A group of proteins, called the male-specific lethal (MSL) complex, is responsible for carrying out this role. These findings made the UT group interested in if this mechanism also occurs in the male germ cells. Distinct molecular events occur in the PGCs during embryonic development between male and female fruit flies.

"'The MSL complex leaves a signature mark, called acetylation, on a specific amino acid of the histone H4 protein of the X chromosome," says Professor Satoru Kobayashi, senior author of the study. "The acetyl group being added tells the cell to express the X-linked genes at a higher level, which results in dosage compensation."

"To address their questions, the researchers used a process called transcriptome analysis to compare gene expression levels between male and female fruit fly PGCs. They also examined the histone H4 protein to determine if acetylation had occurred.

"'We found that X-linked gene expression in male PGCs was about half that of female PGCs," describes Professor Kobayashi. "We also could not detect the acetylation signature of the MSL complex."

"The authors also determined that the main components of the MSL complex are only present in very low amounts in the fly PGCs. Interestingly, they then created transgenic flies that were engineered to express higher levels of the MSL complex proteins. Male PGCs in these flies showed greater activation of X-linked genes, as well as the acetylation signature."

Comment: A complex mechanism to handle x chromosomes properly requires precise design.

https://physicsworld.com/a/make-or-break-building-soft-materials-with-dna/

"DNA molecules are constantly getting broken up and glued back together again with a new topology (figure 2). But there’s one big difference: the DNA needs to preserve its genetic sequence otherwise cells might die or diseases could be triggered.

***

"Nature requires proteins to perform topological operations on DNA while maintaining the original information (the DNA sequence) intact.

"This has a fundamental impact on how topological operations are performed on DNA. Unlike worm-like micelles – where the operations can occur at random anywhere along the micelle and at any time – the topological changes on DNA have to happen at the right place and the right time (they have to be “regulated” as biologists love to say).

***

"To break DNA, for example, you need “restriction enzymes”, which cut the chain only where a certain DNA sequence is recognized. Topoisomerase proteins, meanwhile, have to be precisely positioned at certain locations on chromosomes where entanglements and mechanical stress often accumulate. Similarly, when two pieces of DNA reconnect and recombine – for example when parental genetic material is shuffled in gametes (the precursor of egg and sperm cells) – the process is tightly regulated in space and time to avoid aberrant chromosomes in cells. It’s almost as if DNA (thanks to proteins) is a smart worm-like micelle."

Comment: To do this type of research the author must use enzymes that are used by life's processes. He cannot just step in on his own and invent new chemistry. He is dealing with designed molecules that have electrochemical properties, which by design produce very specific results. However by learning how to manipulate DNA with the proper enzymes, he can produce artificial DNA with new properties. Using CRISPR to slice and dice DNA is one current example.

https://phys.org/news/2021-02-genes-repeatedly-evolution.html

"A study, "Recurrent Evolution of Vertebrate Transcription Factors by Transposase Capture," published Feb. 19 in Science, investigates how genetic elements called transposons, or "jumping genes," are added into the mix during evolution to assemble new genes through exon shuffling.

***

"The study, which focused on tetrapods (four-limbed vertebrates), is important because it shows that transposons represent an important force in the creation of new genes during evolution. The work also explains how genes critical for human development were born.

***

"'You are putting the bricks in in a different way and you construct a whole new thing," Feschotte said. "We are looking at the question of how genes are born. The originality is that we are looking at the role of transposons in creating proteins with novel function in evolution."

***

"The researchers identified more than 100 distinct genes fused with transposases born in the past 350 million years along different species lineages, including genes in birds, reptiles, frogs, bats and koalas, and a total of 44 genes born this way in the human genome.

"Cosby and colleagues selected four recently evolved genes and performed a wide range of experiments in cell culture to understand their functions. They found the proteins derived from these genes are able to bind to specific DNA sequences and turn off gene expression. Such genes are known as transcription factors and act as master regulator genes for development and basic physiology. One such gene, PAX6, is well studied, plays a key role as a master regulator in the formation of eyes in all animals and is highly conserved throughout evolution.

"'If you put a PAX6 gene from a mouse into a Drosophila [fruit fly], it works," Feschotte said. Though others have proposed before that PAX6 is derived from a transposase fusion, the researchers in this study further validated the hypothesis.

"Cosby and colleagues isolated one of these recently evolved genes in bats, called KRABINER, and then used CRISPR gene-editing technology to delete it from the bat genome and see what genes were affected, before adding it back in. The experiment revealed that when KRABINER was removed, hundreds of genes were dysregulated, and when they restored it, normal functioning returned. The protein expressed by the KRABINER gene bound to other related transposons in the bat genome, Cosby said.

"'The experiment revealed that it controls a large network of other genes wired through the past dispersion of related transposons throughout the bat genome—creating not just a gene but what is known as a gene regulatory network," Feschotte said."

Comment: We know that transposons jump around, but not what controls the jumping. Chance or programmed? There is not much non-purposeful DNA. It is really strange that humans are so complex with so few genes.

https://phys.org/news/2020-01-mechanisms-genome.html

"Like a dimmer light switch, each gene can be turned on (expressed) strongly or weakly, or turned off entirely. Individual cells have different gene expression profiles, which enables them to have the different functions that make them part of different tissues. For example, an immune cell expresses proteins that allow it to recognize harmful intruders, while a neuron expresses proteins that enable it to pass nerve signals to its neighbors.

"The ability for a cell to repress genes, keeping them silent, is therefore critical.

***

"The first paper looks at how cells silence transposons, parasitic genetic elements that, if not tightly controlled, are able to jump from one place to another in the genome and cause mutations in other genes while increasing their own numbers. It was known that nucleic acid molecules called piRNAs are able to recognize and suppress harmful transposons, but how they did so was unclear. In the new research, the authors report that piRNAs work together with a small protein called SUMO (small ubiquitin-like protein) that works as a tag that is attached to other proteins. piRNAs and SUMO cooperate to modify chromatin on these selfish transposons and repress them.

"The second paper focuses on roles of SUMO and chromatin in control of normal cellular genes. There are, broadly, two main classes of chromatin: heterochromatin and euchromatin.

"Euchromatin comprises the most actively expressed genes in the genome, while the genes in heterochromatin, it was believed, tend to be silenced. This new research breaks the existing paradigm and suggests that genes residing in heterochromatin are expressed because of their chromatin environment and not despite it.

"'We now know that SUMO acts as a silencing mark to suppress transposons that would otherwise interfere with the proper expression of heterochromatin genes. This is an unexpected function of SUMO," says postdoctoral scholar Maria Ninova, first author on the two new studies.

"The Caltech researchers also found that heterochromatin restricts gene expression to specific tissues and identified a novel mechanism that allows cells to maintain the proper balance between heterochromatin and euchromatin."

Comment: A finding that had to exist. All cells have the same DNA at the start.

https://www.the-scientist.com/features/alternative-splicing-provides-a-broad-menu-of-pr...

"Thanks to the advancement of large-scale proteomic studies over the decade following that milestone, researchers realized that some human cells contain billions of different polypeptides. Researchers realized that each gene can encode an array of proteins. The process of alternative splicing, allows a cell to generate different RNAs, and ultimately different proteins, from the same gene...it has become clear that alternative splicing is common and that the phenomenon helps explain how limited numbers of genes can encode organisms of staggering complexity. While fewer than 40 percent of the genes in a fruit fly undergo alternative splicing, more than 90 percent of genes are alternatively spliced in humans. (my bold)

"Astoundingly, some genes can be alternatively spliced to generate up to 38,000 different transcript isoforms, and each of the proteins they produce has a unique function. Like the chapters of a book, coding segments of the genome, known as exons, appear in series, and alternative splicing works by including or leaving out some of these genomic passages. Some chapters are required—that is, they are found in every transcript—and some are optional, so-called alternative exons. The differential splicing of these regions from an RNA transcript creates customized and condensed genetic messages. Molecular editors control the complicated flurry of exon selection by recognizing the chapters needed for a given protein and discarding the others. The final arrangement of exons in a spliced RNA molecule shapes the resulting protein’s structure and function.

***

"(ENCODE) project was launched to identify the functional elements in the human genome, and the effort ignited controversies as to whether introns were genetic “junk” that the cell invested precious energy and resources to transcribe only to trash prior to translation. Alternative splicing gave these seemingly nonfunctional elements an essential role in gene expression, as evidence emerged over the next few years that there are sequences housed within introns that can help or hinder splicing activity. These enhancer and silencer sequences are recognized by RNA-binding proteins (RBPs) whose presence affects spliceosome docking and assembly. RBPs allow exons or portions of exons to be combined or skipped in unique patterns, such that a single transcript can be spliced into several possible mature mRNA isoforms, or splice variants, each translated into proteins with potentially diverse functions. (my bold)

***

"Each splicing event requires three components: the splice donor, a GU nucleotide sequence at one end of the intron; a splice acceptor, an AG nucleotide sequence at the opposite end; and a branch point, an A approximately 20–40 nucleotides away from the splice acceptor. These three “splice sites” are recognized by two core small nuclear RNAs (snRNAs) of the spliceosome, U1 and U2, followed by a protein, U2AF. The binding of these molecules to a transcript recruits a complex of three more snRNAs—U4, U5, and U6—which facilitates the splicing reaction.

"A variety of factors affect how transcripts from a particular gene are spliced. Exon recognition by the spliceosome can be influenced by RNA binding proteins (RBPs), which bind to enhancer and silencer motifs within the mRNA and help or hinder spliceosome recognition of the splice sites. And because pre-mRNAs are frequently spliced as they’re transcribed, the speed of transcription by RNA polymerase II further tunes the window of opportunity for splice site recognition by the spliceosome.

***

" their studies revealed that every tissue in the body is characterized by a unique set of splicing events...They found that brain, heart, and skeletal muscle present with the most highly conserved and tissue-specific alternative splicing patterns, further underscoring the functional importance of tissue-specific alternative splicing.

***

" Giudice, found that numerous differentially spliced genes encode proteins involved in intracellular trafficking, and these splicing events are controlled by two RBPs: CELF and MBNL. All signs pointed to a splicing network. Follow-up work revealed that the expression levels of CELF and MBNL are inversely tied to one another during muscle development, and that they antagonistically regulate more than 1,000 pre-mRNA transcripts, some of which are translated into proteins critical for muscle contraction.

***

"Researchers are also exploring the possibility that chromatin architecture and epigenetics serve as another layer of splicing regulation by modulating the rate of RNAPII transcription."

Comment: Junk DNA is gone. The complexity of the human genome is only partially unraveled and what is revealed so far is an irreducible complex system that MUST be the result of design. It is highly controlled, especially in fetus formation or abnormal results will produce a defective fetus. This can only be the result of design. A designer is required.

https://phys.org/news/2020-01-chromatin-d-forests-cells.html

"A single cell contains the genetic instructions for an entire organism. This genomic information is managed and processed by the complex machinery of chromatin—a mix of DNA and protein within chromosomes whose function and role in disease are of increasing interest to scientists.

"A Northwestern University research team—using mathematical modeling and optical imaging they developed themselves—has discovered how chromatin folds at the single-cell level. The researchers found chromatin is folded into a variety of tree-like domains spaced along a chromatin backbone. These small and large areas are like a mixed forest of trees growing from the forest floor. The overall structure is a 3-D forest at microscale.

"Chromatin is responsible for packing DNA into the cell nucleus. In humans, that's about six feet of DNA in each cell. The new work suggests that chromatin is more structured and hierarchical in single cells than previously thought. Learning how chromatin correctly operates will help scientists understand what goes wrong with it in cancer and other diseases.

"'By integrating theoretical and experimental work, we have produced a new chromatin folding picture that helps us see how the 3-D genome is organized at the single-cell level," said Igal Szleifer, the Christina Enroth-Cugell Professor of Biomedical Engineering at Northwestern's McCormick School of Engineering.

***

"'If genes are the hardware, chromatin is the software," said Backman, the Walter Dill Scott Professor of Biomedical Engineering and director of the Center for Physical Genomics and Engineering. "If the structure of chromatin changes, it can alter the processing of the information stored in the genome, but it does not alter the genes themselves. Understanding chromatin folding holds the key to understanding how cells differentiate and how cancer happens.'"

Comment: The 3-D relationships determines how the genes are fully interpreted. It is one of the various layers of complex information and instructions that makes each type of cell unique..

DAVID: The 3.8 byo program allows the organisms to modify their DNA only for adaptations to immediate needs which provide minor changes within species. That is how I view Shapiro. Elsewhere I have provided evidence for the initial program completely providing everything (all info) from the beginning.

dhw: This makes no sense. Presumably your first sentence refers to Shapiro’s hypothesis of “natural genetic engineering” (and my hypothesis of cellular intelligence as the designer of innovations), and not to your 3.8 byo programme, and your objection merely echoes the point I made myself, now in bold below.*** There is no evidence for a 3.8 byo programme for every change in the history of evolution, and when I gave you a choice, you opted for a God-given autonomous mechanism! How does an autonomous mechanism support the hypothesis that every change was preprogrammed?

The preprogramming allows for animals to make minor adaptations within the same species by adjusting the DNA in genes as necessary for changing circumstances. Note I said above "modify their DNA only for adaptations to immediate needs which provide minor changes within species." You and Shapiro are not describing a speciation method, only a minor adaptation ability.

***Dhw: Cells can alter their own DNA and their own structures. We do not know the extent to which they can do this, which is why Shapiro’s “natural genetic engineering”, or my more explicit concept of autonomous (possibly God-given) cellular intelligence as the inventor of innovations, remains a hypothesis.

DAVID: Animals are designed to fit their environments requirements which can change requiring new design or extinction. 'Bad luck' still applies. God steps in where He wishes.

dhw: I’m glad you now acknowledge the vital importance of environmental influence. It is indeed bad luck if organisms can’t use their possibly God-given autonomous intelligence to solve new problems. If God exists, then of course he can dabble if he wishes, and the theistic version of my hypothesis has always allowed for this. Chixculub might be an example. (The atheistic version would be that environmental change is purely by chance – bad luck in some cases, and good in others – though it is also possible that your God set up a system to engender random environmental change.)

DAVID: Of course environment plays a huge role as when mammals entered water permanently, but design for survival is required. Note design is primary.

dhw: I don’t know what you mean by “primary”. Are you referring to your theory that your God changed legs to fins before sending pre-whales into the water, all for the sake of complexity - not survival - although fins are no more complex than legs?

Of course, primary always means first, and is this case design is first.

DAVID: The 3.8 byo program allows the organisms to modify their DNA only for adaptations to immediate needs which provide minor changes within species. That is how I view Shapiro. Elsewhere I have provided evidence for the initial program completely providing everything (all info) from the beginning.

This makes no sense. Presumably your first sentence refers to Shapiro’s hypothesis of “natural genetic engineering” (and my hypothesis of cellular intelligence as the designer of innovations), and not to your 3.8 byo programme, and your objection merely echoes the point I made myself, now in bold below.*** There is no evidence for a 3.8 byo programme for every change in the history of evolution, and when I gave you a choice, you opted for a God-given autonomous mechanism! How does an autonomous mechanism support the hypothesis that every change was preprogrammed?

***Dhw: Cells can alter their own DNA and their own structures. We do not know the extent to which they can do this, which is why Shapiro’s “natural genetic engineering”, or my more explicit concept of autonomous (possibly God-given) cellular intelligence as the inventor of innovations, remains a hypothesis.

DAVID: Animals are designed to fit their environments requirements which can change requiring new design or extinction. 'Bad luck' still applies. God steps in where He wishes.

dhw: I’m glad you now acknowledge the vital importance of environmental influence. It is indeed bad luck if organisms can’t use their possibly God-given autonomous intelligence to solve new problems. If God exists, then of course he can dabble if he wishes, and the theistic version of my hypothesis has always allowed for this. Chixculub might be an example. (The atheistic version would be that environmental change is purely by chance – bad luck in some cases, and good in others – though it is also possible that your God set up a system to engender random environmental change.)

DAVID: Of course environment plays a huge role as when mammals entered water permanently, but design for survival is required. Note design is primary.

I don’t know what you mean by “primary”. Are you referring to your theory that your God changed legs to fins before sending pre-whales into the water, all for the sake of complexity - not survival - although fins are no more complex than legs?

dhw: This may be a red letter day in the history of the AgnosticWeb!

DAVID: No letter. I've always accepted Shapiro's studies that shows bacteria can alter their DNA. In Lenski's studies with perpetual E. coli colonies they alter their use of glucose and citrate. Both mechanisms of metabolism are present, but they are able to shift when necessary to what is available and that requires some change in DNA. The 3.8 byo program gets evidence from this knowledge.

dhw: Evolution requires changes in the DNA. I gave you the choice between a 3.8 byo programme for all the changes and a mechanism which enabled the cells to change AUTONOMOUSLY in response to changing conditions. You went for the mechanism, and believe that your God gave it to the cells. If they can change their own DNA autonomously, how does that provide evidence for a 3.8 byo programme for all the changes?

The 3.8 byo program allows the organisms to modify their DNA only for adaptations to immediate needs which provide minor changes within species. That is how I view Shapiro. Elsewhere I have provided evidence for the initial program completely providing everything (all info) from the beginning

DAVID: Cells in legs cannot decide to create fins and design them. Cells simply can alter metabolism as shown above.

Cells can alter their own DNA and their own structures. We do not know the extent to which they can do this, which is why Shapiro’s “natural genetic engineering”, or my more explicit concept of autonomous (possibly God-given) cellular intelligence as the inventor of innovations, remains a hypothesis.

DAVID: Animals are designed to fit their environments requirements which can change requiring new design or extinction. 'Bad luck' still applies. God steps in where He wishes.

dhw: I’m glad you now acknowledge the vital importance of environmental influence. It is indeed bad luck if organisms can’t use their possibly God-given autonomous intelligence to solve new problems. If God exists, then of course he can dabble if he wishes, and the theistic version of my hypothesis has always allowed for this. Chixculub might be an example. (The atheistic version would be that environmental change is purely by chance – bad luck in some cases, and good in others – though it is also possible that your God set up a system to engender random environmental change.)

Of course environment plays a huge role as when mammals entered water permanently, but design for survival is required. Note design is primary.

DAVID: The only issue here is I believe God gave the cells that mechanism.

dhw: This may be a red letter day in the history of the AgnosticWeb!

DAVID: No letter. I've always accepted Shapiro's studies that shows bacteria can alter their DNA. In Lenski's studies with perpetual E. coli colonies they alter their use of glucose and citrate. Both mechanisms of metabolism are present, but they are able to shift when necessary to what is available and that requires some change in DNA. The 3.8 byo program gets evidence from this knowledge.

Evolution requires changes in the DNA. I gave you the choice between a 3.8 byo programme for all the changes and a mechanism which enabled the cells to change AUTONOMOUSLY in response to changing conditions. You went for the mechanism, and believe that your God gave it to the cells. If they can change their own DNA autonomously, how does that provide evidence for a 3.8 byo programme for all the changes?

dhw: Once more I must thank you for your admirable integrity in offering us an article which supports the hypothesis you have so long resisted. It even uses my own favourite analogy of ant colonies. Shapiro champions cellular intelligence, and I don’t see how any organism that “learns” and creates instructions on the hoof (as opposed to being preprogrammed) can be seen as an automaton.

DAVID: The ability to alter metabolism can well be a 3.8 byo programmed ability.

You are playing with words. The ability to make changes autonomously would be 3.8 byo. That is what I have proposed. Your proposal has been that cells are automatons and all the individual changes were programmed in the first cells 3.8 billion years ago.

DAVID: You are still using environmental changes to push evolution, but some one or some thing has to do the designing for the large body changes.

dhw: Yes of course I am. Fins would not be much use if the pre-whale hadn’t taken to the water. You have just agreed that the ‘some thing’ is the cells themselves containing the mechanism which enables them to change autonomously as conditions change (provided God invented the mechanism).

DAVID: Cells in legs cannot decide to create fins and design them. Cells simply can alter metabolism as shown above.

Cells can alter their own DNA and their own structures. We do not know the extent to which they can do this, which is why Shapiro’s “natural genetic engineering”, or my more explicit concept of autonomous (possibly God-given) cellular intelligence as the inventor of innovations, remains a hypothesis.

DAVID: Animals are designed to fit their environments requirements which can change requiring new design or extinction. 'Bad luck' still applies. God steps in where He wishes.

I’m glad you now acknowledge the vital importance of environmental influence. It is indeed bad luck if organisms can’t use their possibly God-given autonomous intelligence to solve new problems. If God exists, then of course he can dabble if he wishes, and the theistic version of my hypothesis has always allowed for this. Chixculub might be an example. (The atheistic version would be that environmental change is purely by chance – bad luck in some cases, and good in others – though it is also possible that your God set up a system to engender random environmental change.)

dhw: The question is not whether DNA editing happens, but whether your God’s “information/instructions used by the cell” means a specific, 3.8-billion-year-old programme for every single change in the history of evolution, switched on automatically by the cell when conditions require or allow it – which seems to me extremely unlikely – or a mechanism which enables the cell to change itself autonomously, i.e. to devise its own programme as conditions change. Shapiro clearly believes in the latter.

DAVID: The only issue here is I believe God gave the cells that mechanism.

dhw: I’ve read this through several times, and I’m still not sure that I dare to celebrate. Can it really be true that you have jettisoned the hypothesis of the first cells containing a 3.8-billion-year old programme for every change, and are now in favour of an autonomous mechanism whereby cells change in response to changing conditions? (I have always allowed for your God being the inventor of the mechanism.) This may be a red letter day in the history of the AgnosticWeb!

No letter. I've always accepted Shapiro's studies that shows bacteria can alter their DNA. In Lenski's studies with perpetual E. coli colonies they alter their use of glucose and citrate. Both mechanisms of metabolism are present, but they are able to shift when necessary to what is available and that requires some change in DNA. The 3.8 byo program gets evidence from this knowledge.

dhw: Quotes from “Genome complexity: DNA tiny part of the controls”: "Accordingly, even single cells change their metabolic pathways, and the way they use their genes to suit those patterns. That is, they “learn,” and create instructions on the hoof. Genes are used as templates for making vital resources, of course. But directions and outcomes of the system are not controlled by genes. Like colonies of ants or bees, there are deeper dynamical laws at work in the development of forms and variations.

"In a paper in Physics of Life Reviews in 2013, James Shapiro describes how cells and organisms are capable of “natural genetic engineering.” That is, they frequently alter their own DNA sequences, rewriting their own genomes throughout life. The startling implication is that the gene as popularly conceived—a blueprint on a strand of DNA, determining development and its variations—does not really exist."

Once more I must thank you for your admirable integrity in offering us an article which supports the hypothesis you have so long resisted. It even uses my own favourite analogy of ant colonies. Shapiro champions cellular intelligence, and I don’t see how any organism that “learns” and creates instructions on the hoof (as opposed to being preprogrammed) can be seen as an automaton.

The ability to alter metabolism can well be a 3.8 byo programmed ability.

DAVID: You are still using environmental changes to push evolution, but some one or some thing has to do the designing for the large body changes.

dhw: Yes of course I am. Fins would not be much use if the pre-whale hadn’t taken to the water. You have just agreed that the ‘some thing’ is the cells themselves containing the mechanism which enables them to change autonomously as conditions change (provided God invented the mechanism).

Cells in legs cannot decide to create fins and design them. Cells simply can alter metabolism as shown above. Animals are designed to fit their environments requirements which can change requiring new design or extinction. 'Bad luck' still applies. God steps in where He wishes.

DAVID: The only issue here is I believe God gave the cells that mechanism.

I’ve read this through several times, and I’m still not sure that I dare to celebrate. Can it really be true that you have jettisoned the hypothesis of the first cells containing a 3.8-billion-year old programme for every change, and are now in favour of an autonomous mechanism whereby cells change in response to changing conditions? (I have always allowed for your God being the inventor of the mechanism.) This may be a red letter day in the history of the AgnosticWeb!

Quotes from “Genome complexity: DNA tiny part of the controls”: "Accordingly, even single cells change their metabolic pathways, and the way they use their genes to suit those patterns. That is, they “learn,” and create instructions on the hoof. Genes are used as templates for making vital resources, of course. But directions and outcomes of the system are not controlled by genes. Like colonies of ants or bees, there are deeper dynamical laws at work in the development of forms and variations.

"In a paper in Physics of Life Reviews in 2013, James Shapiro describes how cells and organisms are capable of “natural genetic engineering.” That is, they frequently alter their own DNA sequences, rewriting their own genomes throughout life. The startling implication is that the gene as popularly conceived—a blueprint on a strand of DNA, determining development and its variations—does not really exist."

Once more I must thank you for your admirable integrity in offering us an article which supports the hypothesis you have so long resisted. It even uses my own favourite analogy of ant colonies. Shapiro champions cellular intelligence, and I don’t see how any organism that “learns” and creates instructions on the hoof (as opposed to being preprogrammed) can be seen as an automaton.

DAVID (under “Gulls change wing shape”): Helps them glide and fly in different ways:
https://techxplore.com/news/2019-01-zoologists-reveal-gulls-wing-morph.html

DAVID: It is not known if the original gulls had this ability from the beginning or developed it over time. If it wasn't present in the beginning they had trouble hunting over the oceans so one can wonder how they survived until they developed these adaptations of elbow joints which require exact design.

dhw: Perhaps they initially found plenty of food close at wing (like pre-whales having plenty of food close at leg) but then conditions changed and they had to hunt further afield, which occasioned the changes made by the cell communities that constitute the wings and their connections.

DAVID: You are still using environmental changes to push evolution, but some one or some thing has to do the designing for the large body changes.

Yes of course I am. Fins would not be much use if the pre-whale hadn’t taken to the water. You have just agreed that the ‘some thing’ is the cells themselves containing the mechanism which enables them to change autonomously as conditions change (provided God invented the mechanism).