Top ten cellular mechanisms that point to Design and Creation

Top ten cellular mechanisms that point to Design and Creation

It takes a lot more faith to believe in the theory of evolution than to believe in God.

1. Motor proteins transferring cargo. They are 'two-legged' top speed protein complexes that run at microtubules without colliding with each other. Collision prevention is done by coded traffic rules. They can run at huge speed, proportional to cars, 300 km/h (180 mph).
   
   
   
   
   
2. The MO-1 marine bacteria have seven complex ion flow motors synchronized with a 24-gear planetary gearbox for producing maximum power. They achieve an incredible speed, proportional to human swimming speed, 100 km/h (60 mph). Fine-tunable torque. Forward-backward directions with extremely rapid (1/4 round) change. Efficiency is better than in any human designed electric motor.
   
   
   
   
   
3. The cell is able to modify DNA bases intentionally along to adaptational needs. This can be done with specific enzymes such as APOBEC3 and A3G. Beneficial DNA alterations are no random changes.
   
   
4. The cell is able to modify any RNA bases with specific enzymes belonging to APOBEC and ADAR families.
   
   
5. The cell is able to produce tens of thousands of different proteins by reading one DNA sequence without modifying DNA. This mechanism is called Alternative Splicing.
   
   
   
   
   
6. Histone code. Histone epigenetic markers represent a biological registry database. DNA is wrapped around histones (compression protein coils), Every histone coil has 8 tails that may carry tens or even hundreds of epigenetic markers. There are over 15 different types of almost atom sized markings. Each marker acts as a memory marker for epigenetic regulation. The histone code is necessary for cellular differentiation. It's inherited by transmission of non coding RNA.
   
   
   
   
   
7. A/D converters in the cell. There are both analog and digital information in the cell. Methylation profiles are analog information, histone markers are digital information. Some histone markings cause the chromatin to be folded and this affects transcriptional activity.
   
   
8. ATP. Another motor structure in the cell.
   
   
   
   
   
   
9. The total volume of DNA of every living taxonomic families is extremely small. It would fit into a mosquito's proboscis.
   
   
10. DNA repair mechanisms. There are several complex epigenetic driven mechanisms being able to rapidly repair different types of DNA damage. How do those proteins recognize which sequence is not valid? How do they recognize the correct DNA sequence?
    
    
    
    
    

Evolutionary Agenda vs True Science

Evolutionary Agenda vs True Science

Evolution believers use the same arguments by which they try to maintain their pseudoscientific theory. Here we compare those typical arguments and claims with serious scientific observations regarding organismal change and what it results in.

The theory of evolution	Serious science
Organisms change due to random genetic mutations. Natural selection means survival of the fittest. This means that individuals having the best characteristics and traits regarding adaptational needs will be better able to reproduce. This results in the trait being more common in population. Change happens slowly, after millions of years. An example: Mutations in Darwin's finches have driven some of them to seed eaters, others to insect eaters etc.	Organisms change due to epigenetic regulation. There is no need for changes in DNA in order to the organism being able to adapt to changing environment. Change is based on coded epigenetic mechanisms: signals, encoding, decoding, responses, regulation. These changes are inheritable but they are dynamic and reversible. An example: When Darwin's finches start to eat seeds, the nutritional compounds affect the birds' epigenome that transmit signals to their cells. This will result in changes in their cellular epigenetic mechanisms and factors. Change occurs rapidly, just in a couple of generations. Offspring will have stronger beaks.
Mechanisms of evolution: Random mutations and Natural selection.	Random mutations are results of genetic entropy. They are not beneficial alterations but harmful changes that lead to genetic load. There are 1,134,942 harmful genetic mutations in human genome worldwide but the number of fully beneficial mutations is 0.
Speciation is evolution.	The most significant mechanisms behind speciation are alternative splicing and RNA-editing. There's no need for DNA changes in order to have new species. Speciation is nothing more but variation within basic groups (kinds) of organisms.
DNA controls cellular mechanisms.	Epigenetic mechanisms control reading (transcription), marking (methylation), repair and even writing to DNA. Specific enzymes such as APOBEC3 and A3G are capable of editing DNA bases along to adaptational needs.
DNA dictates organismal traits and characteristics.	Because virtually every cell in an organism contains the same DNA, then there has to be another information layer that controls cellular differentiation, tissue type, organ function and body plan. This regulatory information layer is called epigenetic mechanisms and factors.

Top ten reasons why I don't believe in the theory of evolution

Top ten reasons why I don't believe in the theory of evolution

1. Human vs. chimp DNA is only ~85% similar at whole genome level. You may have heard of 98.5% similarity but this is true only by comparing so called protein coding DNA. At protein coding DNA, our DNA is also 98.5% similar with dolphins and pigs, for example. 2. DNA similarity is a wrong way to make predictions about possible phylogenetic relationships between organisms. By comparing non coding RNAs, we will have very different results and a duelling evolutionary tree. You can read about this: https://www.gene-quantification.de/dolgin-rewriting-evolution-2012.pdf 3. Organ transplantations from chimps to humans have been unsuccessful. But soon thousands of people are living normal life after getting a liver, a kidney or even a heart from a pig. Even blood transfusion is not possible from chimp to human. 4. Human/chimp epigenomes are very different. Especially histone code is totally different. 5. Your every cell has virtually identical DNA (Neurons and T-cells make an exception). Have you ever wondered, why your skin cell is different to your muscle cell? They contain identical DNA! This means DNA doesn't determine cellular differentiation and identity. It also means that DNA doesn't dictate tissue type or organ function. DNA doesn't determine body plan or any other organismal characteristics. These all are determined by epigenetic programming. Evolution is not able to produce programming languages. 6. The cell is able to produce thousands of different proteins only by reading one DNA sequence without modifying the DNA. This incredible technique is called Alternative Splicing. It's the most significant mechanism behind protein diversity and biodiversity. It's epigenetically regulated. 7. There are no fully beneficial random DNA mutations in human genome but there are ~2 million harmful genetic errors in human genome at the whole population level. 8. Incredible cellular mechanisms, specific ADAR/APOBEC enzymes are able to modify RNA and even DNA bases. RNA A-to-I editing resembles human network technology called NAT (Network address translation). Random chance is not able to create masquearading techniques. 9. In every human being, there are all necessary DNA sequences in order to produce all possible human skin color varieties. It's all about how those DNA sections are to be transcribed. And again, due to same DNA in your cells, DNA doesn't dictate the skin color. 10. We can observe rapid speciation due to epigenetic controlled alternative splicing. We can also observe rapid corruption of biological information. Evolution has no mechanism. You are free to change my mind.

Statements that question the theory of evolution

Several professional paleontologists and biologists have called the theory of evolution into question

Charles Darwin: ."(Since) innumerable transitional forms must have existed, why do we not find them imbedded in countless numbers in the crust of the earth? "Origin of Species", p. 162. "Why is not every geological formation and every stratum full of such intermediate links? Geology assuredly does not reveal any such finely graduated organic chain: and this perhaps is the most obvious and gravest objection which can be urged against my theory." "Origin of Species," p. 293.

Stephen J. Gould: "The extreme rarity of transitional forms in the fossil record persist as the trade secret of paleontology. 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 fossils..We fancy ourselves as the only true students of life's history, yet to preserve our favored account of evolution by natural selection we view our data as so bad that we never see the very process we profess to study.""Evolution's Erratic Pace," Natural History, vol. 86 (May 1987), p. 14.

"Although Archaeopteryx is often proposed as a transitional form, "its fossils do not count." Punctuated Equilibria, 1977.

Stephen J. Gould & George Simpson, "New categories above the level of families appear in the record suddenly and are not lead up to by known, gradual, completely continuous transitional sequences." "Evolution's Erratic

Pace", Natural History, May 1977,at 12,12. John G. Fleagle: "the lack of transitional forms hasn't stopped the paleoanthropologists from selecting their favorite candidates for the anthropoid's predecessors."217 Gish quote of Elizabeth Culotta, Science 256:1516, 1992

Alec J. Kelso: "No fossils of transitional forms that link primates to tree shrews (insectivores), or to anything else.

Alec J., Kelso, R.D Martin,. and others "There is thus no evidence in the present world or in the world of the past to link primates to any other creatures. Right at the very start, then, an evolutionary origin of man is invalidated by actual empirical scientific evidence, The primates, as a group, stand completely isolated from all other creatures. From Gish "The Fossils Say No, 1995, p. 216

David Raup & Stephen Stanley: "Unfortunately, the origins of most higher categories are shrouded in mystery: commonly new higher categories appear abruptly in the fossil record without evidence of transitional forms."

Principals of Paleontology, 1971, p. 306. Boyce Rensberger: "The popularly told example of horse evolution, suggesting a gradual sequence of changes from four-toed, or fox-like creatures, living nearly 50 million years ago, to today's much larger one-toe horse, has long been known to be wrong. Instead of gradual change, fossils of each intermediate species appear fully distinct, persist unchanged, and then become extinct. Transitional forms are unknown." "Ideas on evolution Going Through a Revolution among Scientists," Houston chronicle, 5 Nov. 1980, sec. 4, p. 15.
 

Lucy. An artist's impression.

Niles Eldridge: "...there are all sorts of gaps: absence of gradationally intermediate 'transitional forms' between species, but also between larger groups-between, say, families of carnivores, or the orders of mammals. In fact the higher up the Linnaean hierarchy you look, the fewer transitional forms there seem to be." "Monkey Business," p. 65.

Patricia G. Gensel: "We still lack any precise information concerning the presumed aquatic ancestors from which land plants evolved, and the search for evidence of these precursors and of probable transitional stages continues." "The Evolutions of Early Land Plants," American Scientist, Vol. 75, Sept./Oct. 1987, p. 480.

Frank M. Carpenter, "There is, however, no fossil evidence bearing on the question of insect origin; the oldest insects known show no transition to other arthropods." "Fossil Insects," 1952, p. 18.

Henry N. Andrews: "The spore bearing organs of these Permian mosses have not been found, so that more precise comparisons with living forms are not possible. Their importance lies in the fact that they are well-preserved, they are unquestionably mosses, and sufficiently similar to modern ones in their vegetative organization as to suggest no major chnages in moss evolution since that time." "Studies in Paleontology," 1961, p. 401.

Neal Gillespie: "..."species appeared full-blown suddenly, endured unchanged, and became extinct without leaving descendants". Charles Darwin and the Problem of Creation 7, (1979) (U. of Chicago Press). p. 26.

George Simpson: (noted Harvard paleontologist) "The regular absence of transitional forms is an almost universal phenomenon...all orders of classes of animals (and) analogous categories of plants." The Sudden Appearance of Higher Categories, in Evolution of Life. 149 (S. Tax ed. 1960)

Also as (paleontologist Am. Museum of Nat. History) "As it became more and more evident that the great gaps remained despite wonderful progress in finding the members of lower transitional groups and progressive lines, it was no longer satisfactory to impute this absence of objective data entirely to chance. The failure of Paleontology to produce such evidence was so keenly felt that a few disillusioned naturalists even decided that the theory of organic evolution, or general organic continuity of descent was wrong, after all.". "Tempo and Mode of Evolution" (1944), p 115,

Barbara Stahl: "It is not difficult to imagine how feathers, once evolved, assumed additional functions, but how they arose initially, presumably from reptilian scales, defies analysis." "The problem has been set aside, not for lack of interest, but for lack of evidence. No fossil structure transitional between scale and feather is known, and recent investigators are unwilling to found a theory on pure speculation." "It seems, from the complex structure of feathers, that their evolution from reptilian scales would have required an immense period of time and involved a series of intermediate structures. So far, the fossil record does not bear out that supposition." .." "Vertebrate History: Problems in Evolution", McGraw-Hill, N. Y., 1974, p.349-350.

James W. Valentine & Douglas H. Erwin (Valentine is at the U. of Cal. at Santa Barbara, and Erwin at Michigan State U.)"Interpreting Great Developmental Experiments: The Fossil Record," "If ever we were to expect to find ancestors to or intermediates between higher taxa, it would be in the rocks of late Precambrian to Ordovician times, when the bulk of the world's higher animal taxa evolved. Yet transitional alliances are unknown or unconfirmed for any of the phyla or classes appearing then...We conclude that the probability that species selection is a general solution to the origin of higher taxa is not great, and that neither of the contending theories of evolutionary change at the species level, phyletic gradualism or punctuated equilibrium, seem applicable to the origin of new body plans." in "Development as an Evolutionary Process," N. Y., 1987, pp. 84-86.

Ann Gibbons, John Ruben (Lung Structure and Ventilation in Therapod Dinosaurs and Early Birds," Science, Vol. 278, 14 Nov. 1997, pp. 1267-1270) ".. argues that a transition from a crocodilian to a bird lung would be impossible, because the transitional animal would have a life-threatening hernia or a hole in its diaphragm." "Lung Fossils Suggest Dinos Breathed in Cold Blood," Science, Vol. 278, 14 Nov. 1997, p. 1230.

Ernest Lutz: "There is neither evidence of a lineage from reptiles to Archaeopteryx nor from it to any living birds. Further, and also most importantly, natural selection is inadequate as a possible mechanism to explain the descent of Archaeopteryx. In view of the evidence science has oversold the case of Archaeopteryx as a transitional form." "A Review of Claims About Archaeopteryx in the Light of the Evidence," Creation Research Soc. Quarterly, June 1995, p. 18.

Newsweek, Nov. 1980: "In the fossil record missing links are the rule; the story of life is as disjointed as a newsreel, in which species succeed one another as abruptly as Balkan prime ministers. The more scientists have searched for the transitional forms between species, the more they have been frustrated." "Is Man a Subtle Accident?" Newsweek, 3 November, 1980, p. 95.

Colin Patterson: "..."Yet Gould and the American Museum people are hard to contradict when they say there are no transitional fossils... You say I should at least 'show a photo of the fossil from which each type of organism was derived.' I will lay it on the line - there is not one such fossil for which one could make a watertight argument." In letter to Luther Sunderland, April 10, 1979. Cited in: Sunderland, Luther D., Darwin's Enigma: Fossils and Other Problems (El Cajon, CA: Master Books, 1988), p. 89.

Alfred S. Romer: "The origin of the rodents is obscure. When they first appear, in the genus Paramys, we are already dealing with a typical if rather primitive true rodent with the definitive ordinal characters well developed. Presumably of course they had arisen from some basal, insectivorous, placental stock, but no transitional forms are known." "Vertebrate Paleontology," 1966.

Lenski's experiment is a disaster for the theory of evolution

This scientific experiment was meant to prove that evolution was taking place. In the end, it proves the exact opposite.

https://www.nsf.gov/discoveries/disc_summ.jsp?cntn_id=119814&org=NSF&from=news

The experiment was designed to ask about the repeatability of evolution. "If we look at the tension between the randomness of mutation and the predictability of natural selection, how does evolution play out when you put the two together?" Lenski says. "That's really what this long-term experiment has been all about. Over the course of these decades, we've seen all kinds of interesting phenomena."

The long-term evolution experiment (LTEE) with Escherichia coli was started in Feb 24th 1988 with the founding of 12 populations from the same clone.

Mutator genomes decay, despite sustained fitness gains, in a long-term experiment with bacteria

https://www.pnas.org/doi/10.1073/pnas.1705887114

"However, mutation rates can change dramatically over time, and experiments with hypermutable bacteria show that their genomes rapidly decay when propagated under the near absence of selection. Whether selection can prevent this decay is unclear. Here, we document the rapid genome decay of hypermutable bacteria even during tens of thousands of generations of sustained adaptation to a laboratory environment. These findings suggest the need to reexamine current ideas about the evolution of bacterial genomes."

Lenski's long term experiment failed to prove evolution

Extinction

https://evolutionnews.org/2020/06/citrate-death-spiral/

"For example, the citrate mutant had accumulated many of the same beneficial-but-degradative mutations that had previously spread through the population — the new mutation did not, could not, restore them. And later work showed that several more broken genes had been selected in the mutant, apparently to help it metabolize citrate more efficiently.

A Sick Puppy

The new paper now reports on 2,500 generations of further evolution of the citrate mutant, in nutrient media that contains either citrate alone or citrate plus glucose (as for earlier generations). As always with the Lenski lab, the research is well and thoroughly done. But the resulting E. coli is one sick puppy. Inside the paper they report that “The spectrum of mutations identified in evolved clones was dominated by structural variation, including insertions, deletions, and mobile element transpositions.” All of those are exceedingly likely to break or degrade genes. Dozens more genes were lost. The citrate mutant tossed genetic information with mindless abandon for short term advantage.

In a particularly telling result, the authors “serendipitously discovered evidence of substantial cell death in cultures of a Cit+ clone sampled from … the LTEE at 50,000 generations.” In other words, those initial random “beneficial” citrate mutations that had been seized on by natural selection tens of thousands of generations earlier had led to a death spiral. The death rate of the ancestor of the LTEE was ~10 percent; after 33,000 generations it was ~30 percent; after 50,000, ~40 percent. For the newer set of experiments, the death rate varied for different strains of cells in different media, but exceeded 50 percent for some cell lines in a citrate-only environment. Indeed, the authors identified a number of mutations — again, almost certainly degradative ones — in genes for fatty acid metabolism that, they write with admirable detachment, “suggest adaptation to scavenging on dead and dying cells.”

The degraded E. coli was eating its dead."

Adaptation without novel information (the citrate utilization)

https://journals.asm.org/doi/10.1128/JB.00831-15

"We conclude that the rarity of the LTEE mutant was an artifact of the experimental conditions and not a unique evolutionary event. No new genetic information (novel gene function) evolved."

Summary and conclusions:

• During ~75,000 generations of bacterial life, there has been no evolution.
• In these last 34 years the experiment has evidenced a huge number of loss of function mutations, extinction and death.
• Mutator genomes decay rapidly despite sustained fitness gain.
• Adaptation (the citrate utilization) was based on reorganization of existing information.
• No new genetic information (novel gene function) has evolved.
• As a longest scientific experiment meant to prove that evolution is taking place, this experiment is a catastrophe for the theory of evolution. It proves the exact opposite: the more adaptation, the more genetic degradation.

Endogenous retroviruses are no proof of evolution

ERVs support Intelligent Design and Creation

Endogenous Retroviruses Protect Us from Viral Infections

https://journals.asm.org/doi/10.1128/JVI.02299-20

Excerpts: "Long disregarded as junk DNA or genomic dark matter, endogenous retroviruses (ERVs) have turned out to represent important components of the antiviral immune response. These remnants of once-infectious retroviruses not only regulate cellular immune activation, but may even directly target invading viral pathogens. In this Gem, we summarize mechanisms by which retroviral fossils protect us from viral infections. One focus will be on recent advances in the role of ERVs as regulators of antiviral gene expression."

• ERV-derived nucleic acids trigger innate sensing cascades. 
• ERV-derived lncrnas regulate antiviral immune responses.
• Endogenous retroviral proteins modulate immune activation.
• Endogenous retroviral envelope proteins block virus entry receptors.
• ERV proteins complement virions in a dominant negative manner.
• ERV proteins interfere with incoming viral particles.
• Repetitive ERV elements increase plasticity of immunity genes.
• ERV-Derived promoters and enhancers regulate antiviral gene expression.

Cells contain an in-built reverse trancriptase mechanism, by which they are able to store viral RNA sequences by converting them into DNA.

https://www.sciencedaily.com/releases/2021/06/210611174037.htm

Excerpt: "Cells contain machinery that duplicates DNA into a new set that goes into a newly formed cell. That same class of machines, called polymerases, also build RNA messages, which are like notes copied from the central DNA repository of recipes, so they can be read more efficiently into proteins. But polymerases were thought to only work in one direction DNA into DNA or RNA. This prevents RNA messages from being rewritten back into the master recipe book of genomic DNA. Now, Thomas Jefferson University researchers provide evidence that RNA segments can be written back into DNA via a polymerase called theta, which could have wide implications affecting many fields of biology.
"This work opens the door to many other studies that will help us understand the significance of polymerases that can write RNA messages into DNA," says Richard Pomerantz, PhD, associate professor of biochemistry and molecular biology at Thomas Jefferson University. "That polymerase theta can do this with high efficiency, raises many questions." For example, this finding suggests that RNA messages can be used as templates for repairing or re-writing genomic DNA...."Our research suggests that polymerase theta's main function is to act as a reverse transcriptase," says Dr. Pomerantz."

Summary and conclusions:

• So called endogenous retroviruses are no genomic junk. There is no junk-DNA.
• ERV derived molecules and proteins play a significant role for the innate immune system.
• Endogenous Retroviruses Protect Us from Viral Infections
• The cell contains designed mechanisms by which it is able to store (record) viral RNA sequences.
• Endogenous retroviruses support Intelligent Design and Creation.

Epigenetics behind phenotypic differences

Hard evidence that DNA doesn't dictate traits or characteristics

Pigmentation, hair/fur/coat color

https://www.frontiersin.org/articles/10.3389/fgene.2020.603528/full

Excerpt: "Results: We compared genome-wide DNA methylation profiles in Rex rabbit hair follicles in a Chinchilla group (Ch) and a diluted Chinchilla group (DCh) through whole-genome bisulfite sequencing (WGBS). Approximately 3.5% of the cytosine sites were methylated in both groups, of which the CG methylation type was in greatest abundance. In total, we identified 126,405 differentially methylated regions (DMRs) between the two groups, corresponding to 11,459 DMR-associated genes (DMGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these DMGs were principally involved in developmental pigmentation and Wnt signaling pathways. In addition, two DMRs were randomly selected to verify that the WGBS data were reliable using bisulfite sequencing PCR, and seven DMGs were analyzed to establish the relationship between the level of DNA methylation and mRNA expression using qRT-PCR. Due to the limitation of small sample size, replication of the results with a larger sample size would be important in future studies.

Conclusion: These findings provide evidence that there is an association between inherited color dilution and DNA methylation alterations in hair follicles, greatly contributing to our understanding of the epigenetic regulation of rabbit pigmentation."

https://bmcgenomdata.biomedcentral.com/articles/10.1186/s12863-017-0564-9

Excerpt: "Totals of 3434 and 3683 unigenes had significantly lower and higher expression in WCC, respectively, compared with unigenes expressed in RCC. Some potential genes for body color development were further identified by quantitative polymerase chain reaction, such as mitfa, tyr, tyrp1, and dct, which were down-regulated, and foxd3, hpda, ptps, and gch1, which were up-regulated. A KEGG pathway analysis indicated that the differentially expressed genes were mainly related to mitogen activated protein kinase (MAPK), Wnt, cell cycle, and endocytosis signaling pathways, as well as variations in melanogenesis in crucian carp. In addition, some differentially expressed DNA methylation site genes were related to pigmentation, including mitfa, tyr, dct, foxd3, and hpda. The differentially expressed DNA methylation sites were mainly involved in signaling pathways, including MAPK, cAMP, endocytosis, melanogenesis, and Hippo."

Body plan

https://pubmed.ncbi.nlm.nih.gov/27439862/

Excerpt: "Epigenetic patterns of histone modifications contribute to the maintenance of tissue-specific gene expression. Here, we show that such modifications also accompany the specification of cell identities by the NF-κB transcription factor Dorsal in the precellular Drosophila embryo. We provide evidence that the maternal pioneer factor, Zelda, is responsible for establishing poised RNA polymerase at Dorsal target genes before Dorsal-mediated zygotic activation. At the onset of cell specification, Dorsal recruits the CBP/p300 coactivator to the regulatory regions of defined target genes in the presumptive neuroectoderm, resulting in their histone acetylation and transcriptional activation. These genes are inactive in the mesoderm due to transcriptional quenching by the Snail repressor, which precludes recruitment of CBP and prevents histone acetylation. By contrast, inactivation of the same enhancers in the dorsal ectoderm is associated with Polycomb-repressed H3K27me3 chromatin. Thus, the Dorsal morphogen gradient produces three distinct histone signatures including two modes of transcriptional repression, active repression (hypoacetylation), and inactivity (H3K27me3). Whereas histone hypoacetylation is associated with a poised polymerase, H3K27me3 displaces polymerase from chromatin. Our results link different modes of RNA polymerase regulation to separate epigenetic patterns and demonstrate that developmental determinants orchestrate differential chromatin states, providing new insights into the link between epigenetics and developmental patterning."

https://www.sciencedaily.com/releases/2020/12/201216104642.htm

Excerpt: "Researchers have shown that the enzyme lysine demethylase 7a helps ensure the ordered axial development of the mouse embryo by modulating Hox genes which specify positional characteristics along the head-to-tail axis. Their findings suggest that the enzyme modulates Hox gene activation by regulating the repressive histone mark H3K9me2, an epigenetic modification of the DNA packaging protein Histone H3."

Beak size and shape of Darwin's finches

https://www.researchgate.net/publication/319267860_Epigenetic_variation_between_urban_and_rural_populations_of_Darwin's_finches

Excerpt: "We did not find large size copy number variation (CNV) genetic differences between populations of either species. However, other genetic variants were not investigated. In contrast, we did find dramatic epigenetic differences between the urban and rural populations of both species, based on DNA methylation analysis. We explored genomic features and gene associations of the differentially DNA methylated regions (DMR), as well as their possible functional significance. Conclusions In summary, our study documents local population epigenetic variation within each of two species of Darwin’s finches."

Human height

https://pubmed.ncbi.nlm.nih.gov/24963031/

Excerpt: "Genome-wide SNP analyses have identified genomic variants associated with adult human height. However, these only explain a fraction of human height variation, suggesting that significant information might have been systematically missed by SNP sequencing analysis. A candidate for such non-SNP-linked information is DNA methylation. Regulation by DNA methylation requires the presence of CpG islands in the promoter region of candidate genes. Seventy two of 87 (82.8%), height-associated genes were indeed found to contain CpG islands upstream of the transcription start site (USC CpG island searcher; validation: UCSC Genome Browser), which were shown to correlate with gene regulation. Consistent with this, DNA hypermethylation modules were detected in 42 height-associated genes, versus 1.5% of control genes (P = 8.0199e(-17)), as were dynamic methylation changes and gene imprinting. Epigenetic heredity thus appears to be a determinant of adult human height. Major findings in mouse models and in human genetic diseases support this model. Modulation of DNA methylation are candidate to mediate environmental influence on epigenetic traits. This may help to explain progressive height changes over multiple generations, through trans-generational heredity of progressive DNA methylation patterns."

Flower color changes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121637/

Excerpt: "Epigenetic changes caused by methylcytosine modification participate in gene regulation and transposable element (TE) repression, resulting in phenotypic variation. Although the effects of DNA methylation and TE repression on flower, fruit, seed coat, and leaf pigmentation have been investigated, little is known about the relationship between methylation and flower color chimerism. In this study, we used a comparative methylomic–transcriptomic approach to explore the molecular mechanism responsible for chimeric flowers in Prunus mume “Danban Tiaozhi”. High-performance liquid chromatography-electrospray ionization mass spectrometry revealed that the variation in white (WT) and red (RT) petal tissues in this species is directly due to the accumulation of anthocyanins, i.e., cyanidin 3,5-O-diglucoside, cyanidin 3-O-glucoside, and peonidin 3-O-glucoside. We next mapped the first-ever generated methylomes of P. mume, and found that 11.29–14.83% of the genomic cytosine sites were methylated. We also determined that gene expression was negatively correlated with methylcytosine level in general, and uncovered significant epigenetic variation between WT and RT. Furthermore, we detected differentially methylated regions (DMRs) and DMR-related genes between WT and RT, and concluded that many of these genes, including differentially expressed genes (DEGs) and transcription factor genes, are critical participants in the anthocyanin regulatory pathway. Importantly, some of the associated DEGs harbored TE insertions that were also modified by methylcytosine. The above evidence suggest that flower color chimerism in P. mume is induced by the DNA methylation of critical genes and TEs."

Facial characteristics

https://www.whatisepigenetics.com/epigenetics-behind-unique-human-faces/

Excerpt: “This is a novel conceptual framework for understanding how different facial features arise,” Rijli said about the team’s study. “Epigenetic poising may allow cranial neural crest cells to rapidly adapt their response to local variations in environmental signaling, thus potentially explaining differences in facial shape between individuals.”

Specifically, they looked at different chromatin profiles of neural crest cells in various positions prior to and after migration. First author Maryline Minoux said, “in the postmigratory neural crest cells, the promoters of the differentially silenced genes – i.e. genes not expressed in some populations, but expressed in others – were maintained in a bivalent configuration marked by both repressive H3K27me3 and activating H3K4me2 epigenetic histone modifications.”

The histone modifications poised the genes for activation. Interestingly, this configuration was already found in the neural crest cells before they had even begun migration. As soon as the cells are exposed to particular environmental cues, they get rid of the repressive H3K27 trimethylation mark (H3K27me3) and begin to form various facial features.

Additionally, the authors also discovered that the Ezh2 (Enhancer of zeste homolog 2) component of the PRC2 (Polycomb Repressive Complex 2) had a hand in regulating the poised chromatin state. PRC2 is an established chromatin remodeler during the embryo’s development.

Even if the genes responsible for these craniofacial structures are almost the same in each person, epigenetics could contribute to the reason why some people have a more pronounced forehead, high cheekbones, a button nose, or almond-shaped eyes. Although additional research is needed, the study offers novel insights into the epigenetic regulation of the formation of our facial features.

Leaf shape and photosynthesis

https://academic.oup.com/jxb/article/67/3/723/2893338

Excerpt: "To investigate variation in DNA methylation and whether this variation associates with important plant traits, including leaf shape and photosynthesis, 20 413 DNA methylation sites were examined in a poplar association population (505 individuals) using methylation-sensitive amplification polymorphism (MSAP) technology. Calculation of epi-population structure and kinships assigned individuals into subsets (K=3), revealing that the natural population of P. simonii consists of three subpopulations. Population epigenetic distance and geographic distance showed a significant correlation (r=0.4688, P<0.001), suggesting that environmental factors may affect epigenetics. Single-marker approaches were also used to identify significant marker–trait associations, which found 1087 high-confidence DNA methylation markers associated with different phenotypic traits explaining ~5–15% of the phenotypic variance. Among these loci, 147 differentially methylated fragments were obtained by sequencing, representing 130 candidate genes. Expression analysis of six candidate genes indicated that these genes might play important roles in leaf development and regulation of photosynthesis. This study provides association analysis to study the effects of DNA methylation on plant development and these data indicate that epigenetics bridges environmental and genetic factors in affecting plant growth and development."

Skeletal development and morphology

https://www.jbc.org/article/S0021-9258(20)43973-0/fulltext

Excerpt: "Epigenetic control of gene expression is critical for normal fetal development. However, chromatin-related mechanisms that activate bone-specific programs during osteogenesis have remained underexplored. Therefore, we investigated the expression profiles of a large cohort of epigenetic regulators (>300) during osteogenic differentiation of human mesenchymal cells derived from the stromal vascular fraction of adipose tissue (AMSCs). Molecular analyses establish that the polycomb group protein EZH2 (enhancer of zeste homolog 2) is down-regulated during osteoblastic differentiation of AMSCs. Chemical inhibitor and siRNA knockdown studies show that EZH2, a histone methyltransferase that catalyzes trimethylation of histone 3 lysine 27 (H3K27me3), suppresses osteogenic differentiation. Blocking EZH2 activity promotes osteoblast differentiation and suppresses adipogenic differentiation of AMSCs. High throughput RNA sequence (mRNASeq) analysis reveals that EZH2 inhibition stimulates cell cycle inhibitory proteins and enhances the production of extracellular matrix proteins. Conditional genetic loss of Ezh2 in uncommitted mesenchymal cells (Prrx1-Cre) results in multiple defects in skeletal patterning and bone formation, including shortened forelimbs, craniosynostosis, and clinodactyly. Histological analysis and mRNASeq profiling suggest that these effects are attributable to growth plate abnormalities and premature cranial suture closure because of precocious maturation of osteoblasts. We conclude that the epigenetic activity of EZH2 is required for skeletal patterning and development, but EZH2 expression declines during terminal osteoblast differentiation and matrix production."

Macrocilix maia, incredible camouflage

Butterfly wing color patterning

https://www.the-scientist.com/news-opinion/gene-regulation-gives-butterflies-their-stunning-looks-66724

Excerpt: "Distantly related, lookalike Heliconius species arrive at the same appearance using the same few genes, but regulated differently, according to recent studies."

Blind cave fish eye development

https://arstechnica.com/science/2018/06/for-blind-cave-fish-to-see-or-not-to-see-is-a-matter-of-epigenetics/

Excerpt: "There's evidence that altered methylation is central to the changes in these fish. A drug called 5-Azacytidine is an inhibitor of methylation (it's used by people with myelodysplastic syndrome, a rare disorder in which blood cells do not mature properly). Injections of the drug into cave fish embryo eyes could partially rescue their development, confirming that their loss is due to changes in methylation."

Insect metamorphosis

https://www.frontiersin.org/articles/10.3389/fevo.2021.646281/full

Excerpt: "We also identified 4.946 loci and 4.960 regions showing stage-specific differential methylation. Interestingly, genes encoding histone acetyltransferases and histone deacetylases were differentially methylated in the larvae and adults, indicating there is crosstalk between different epigenetic mechanisms. The distinct sets of methylated genes in M. sexta larvae and adults suggest that complete metamorphosis involves epigenetic modifications associated with profound transcriptional reprogramming, involving approximately half of all the genes in this species."

Summary and conclusions:

• Epigenetic mechanisms and factors regulate organismal traits and characteristics.
• DNA has no predictive role for organismal development and variation.
• The following traits/characteristics are regulated by epigenetic mechanisms and factors:
• Pigmentation
• Fur/hair/coat color
• Body plan
• Beak size and shape
• Human height
• Flower color changes
• Facial characteristics
• Leaf shape and photosynthesis
• Skeletal development and morphology
• Butterfly wing color patterning
• Blind cave fish eye development
• Insect metamorphosis

Science is changing. A few years ago we were taught that DNA determines organismal traits and characteristics. Modern science has revealed that epigenetic mechanisms and factors control reading and transcription of DNA. Epigenetic regulation never results in any kind of evolution because there is no mechanism increasing biological information in a way that could result in growth of structural or functional complexity in organisms. Epigenetic modifications only regulate or switch on/off pre-existing biological information. It's all about alternative biological programs. Evolution never happened. Don't get lost, my friends.

Bad news for mankind, human genome is rapidly decaying

Every one of us is carrying hundreds of broken genes - and the number is rapidly increasing

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299548/

Excerpt: "Genetic variants predicted to severely disrupt protein-coding genes, collectively known as loss-of-function (LoF) variants, are of considerable scientific and clinical interest. Traditionally such variants have been regarded as rare and having a high probability of being deleterious, on the basis of their well-established causal roles in severe Mendelian diseases such as cystic fibrosis and Duchenne muscular dystrophy. However, recent studies examining the complete genomes of apparently healthy subjects have suggested that such individuals carry at least 200 and perhaps as many as 800 predicted LoF variants. These numbers imply a previously unappreciated robustness of the human genome to gene-disrupting mutations, and have important implications for the clinical interpretation of human genome sequencing data."

https://www.futuremedicine.com/doi/10.2217/frd-2020-0003

Excerpt: "The immune system is a sophisticated biological system dedicated to fight against foreign antigens, distinguish self from non-self-antigens and eliminate cells that are not growing properly. Consequently, organisms are protected from potentially damaging microorganisms and from infected or abnormally growing cells. The immune system is also designed to tolerate self-antigens and non-pathogenic microorganisms such as commensal microbiota. This concept is referred to as immune tolerance, which involves apoptosis of self-antigen-specific lymphocytes. This process can also be altered by specific genetic defects of the immune system. In consequence, inborn errors of immunity (IEI) or primary immunodeficiency disorders (PIDD) may drive increased susceptibility to infection, autoinflammation, autoimmunity, malignancy or allergy. They are caused by mutations that result in loss (LOF) or gain of function (GOF) of key molecules participating in the immune response. To date, defects in more than 450 genes have been described to cause different IEI phenotypes. These phenotypes are very heterogeneous including: antibody deficiency, T and B lymphocyte deficiency, complement deficiency, autoimmunity, lymphoproliferative syndromes or immune dysregulation. In some cases, immunodeficiency may concur with autoimmunity and/or immune dysregulation, especially when genetic defects compromise molecules that regulate the immune response or are involved in tolerance. Although IEI are considered rare diseases and defects in individual genes may be infrequent; collectively, they can affect a considerable number of individuals."

https://www.disgenet.org/

"The current version of DisGeNET (v7.0) contains 1,134,942 gene-disease associations (GDAs)
(My comment: This number is an update made on Jan. 2021, next update will increase that number close to two million), between 21,671 genes and 30,170 diseases, disorders, traits, and clinical or abnormal human phenotypes, and 369,554 variant-disease associations (VDAs), between 194,515 variants and 14,155 diseases, traits, and phenotypes."

Summary and conclusion:

• Every healthy individual is carrying at least 200 and possibly even 800 genetic defects that are considered as reasons for loss of function variants = broken genes.
• Many LOF (loss of function) genes are directly associated with severe genetic diseases.
• LOF variants have a strong association with a weakened immune system.
• Gain of function variants are also linked to genetic diseases.
• The number of harmful mutations in human genome is growing by rate of 1.5 every year.
• It's very difficult to discover random, fully beneficial DNA mutations.
• Human genome is rapidly deteriorating.
• Evolution is not happening.

Red hair is caused by a broken gene

It's called a mutation, a variant, SNP or polymorphism - Actually it's a genetic error

Polymorphism? A variant?

https://medlineplus.gov/genetics/gene/mc1r/

Excerpt: "Common variations (polymorphisms) in the MC1R gene are associated with normal differences in skin and hair color. Certain genetic variations are most common in people with red hair, fair skin, freckles, and an increased sensitivity to sun exposure. These MC1R polymorphisms reduce the ability of the melanocortin 1 receptor to stimulate eumelanin production, causing melanocytes to make mostly pheomelanin. Although MC1R is a key gene in normal human pigmentation, researchers believe that the effects of other genes also contribute to a person's hair and skin coloring.

The melanocortin 1 receptor is also active in cells other than melanocytes, including cells involved in the body's immune and inflammatory responses. The receptor's function in these cells is unknown."

A mutation?

https://www.degruyter.com/document/doi/10.1016/j.sjpain.2010.08.005/html

Excerpt: "Pain sensitivity has been linked to the melanocortin-1 receptor (MC1R) gene. A mutation in MC1R can result in pale skin and red hair in humans and may modulate pain responses in general. Human studies have shown that women with non-functional MC1R’s were sensitive to experimental induced cold and heat pain. A study demonstrated that females with red hair required higher dose of anesthesia than females with dark hair to experience analgesia to electrical stimulation. Moreover, women expressing non-functional MC1Rs display greater analgesia from opioid analgesia. If redheads in general respond differently to pain and analgesics, this is of clinical importance."

SNP?

https://link.springer.com/article/10.1007/s00439-010-0939-8

"MC1R SNPs are fairly indicative for red hair and thus have already been implemented in forensic science."

It's a broken gene

https://genetics.thetech.org/ask-a-geneticist/repairing-broken-mc1r-gene

Excerpt: "Summer is coming and I would like to get rid of my red hair and fair skin. Is there any way to fix my broken MC1R gene?

-A curious adult from Poland

May 7, 2015

Hi curious adult from Poland! I’m sorry to say the short answer to your question is no we can’t (at least not right now). Sunscreen and the right clothing are still your best bet this summer.

We can’t really fix the broken MC1R gene responsible for your red hair (and fair skin) for a couple of reasons. First off, we are not very good at fixing broken genes yet.

Gene therapy (as fixing broken genes is called) doesn’t work very well and is dangerous to boot! The cure might be worse than the condition in this case. Second, the situation with MC1R is surprisingly complicated. If we could fix your gene, there may be a shot at getting rid of your red hair. But the fair skin is much trickier. No matter how hard we try we may not be able to get rid of that.

...In your case, even if we get the gene in, we still can’t be sure of the results. As you likely know, the protein made by the MC1R gene is important for making pigments in our skin and hair. A mutated gene leads to lighter pigments, in your case red hair and fair skin.

Like most of the rest of our genes, we have two copies of our MC1R gene. We got one copy from our mom, and one from our dad.

Typically, you need both of your MC1R gene copies to be of the red type to have red hair. (This is called a recessive trait.) So, having one not-red MC1R gene around would mean bye-bye red hair, right? Well not exactly. Sometimes people who have one, or even two, not-red versions, still have red hair!. So, adding in the new copy may not mean good-bye red hair."

"

https://www.ncbi.nlm.nih.gov/gene/4157

"Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer."

MC1R mutations lead to a weakened immune system

https://pubmed.ncbi.nlm.nih.gov/30278967/

Excerpt: "This is the first study to demonstrate a significant association between genetic polymorphisms and a nonfatal burn-induced SIRS complication. Our findings suggest that MC1R polymorphisms contribute to dysfunctional responses to burn injury that may predict infectious and inflammatory complications."

https://europepmc.org/article/med/25155575

Excerpt: "Persons with red hair have mutations in the MC1R causing its inactivation; this leads to a paucity of eumelanin production and makes red-heads more susceptible to skin cancer. Apart from its effects on melanin production, the α-MSH/MC1R signaling is also a potent anti-inflammatory pathway and has been shown to promote antimelanoma immunity. This review will focus on the role of MC1R in terms of its regulation of melanogenesis and influence on the immune system with respect to skin cancer susceptibility."

Papers about MC1R connections to the immune system:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758465/
https://www.frontiersin.org/articles/10.3389/fphar.2018.01535/full
https://www.nature.com/articles/s41598-020-64305-9

Summary and conclusions:

• Red hair is often explained as normal genetic variation, a gene allele, a SNP, a variant or so called polymorphism.
• We are taught that definition of evolution is change in allele frequency.
• Actually MC1R mutations (change in allele frequency) are genetic errors resulting in loss of function and a weakening immune system.
• The MC1R gene is widely used for several purposes in human cells. As in pigment production, it is also necessary for a properly functioning immune system.
• Human DNA is organized in highly sophisticated way; it doesn't tolerate mutations (genetic errors).
• Having a MC1R mutation doesn't always predict red hair. MC1R only explains 73% of the SNP heritability for red hair in UK Biobank.
• MC1R mutations are examples of genetic entropy. They have nothing to do with assumed evolution.

Binary fission and bacterial lifespan destroy the evolutionary theory

Complex DNA replication machinery couldn't have evolved during one bacterial life cycle

Binary fission

Asexual reproduction by a separation of the body into two new bodies. In the process of binary fission, an organism duplicates its genetic material, or deoxyribonucleic acid (DNA), and then divides into two parts (cytokinesis), with each new organism receiving one copy of DNA. (britannica.com)

https://www.sciencefocus.com/nature/how-long-does-a-bacterium-live/

How long does a bacterium live?

"But if we assume that the global bacteria population is stable, then it follows that one bacterium must die for each new one that is produced. Bacteria divide somewhere between once every 12 minutes and once every 24 hours. So the average lifespan of a bacterium is around 12 hours or so."

So, if someone claims evolution took place within first assumed bacteria (or other prokaryotes), then he/she believes that one bacterium evolved the complex DNA replication machinery just during ONE BACTERIAL LIFE CYCLE. In 12 hours or so!! And now we have to have a look at this complex DNA replication mechanism:

https://www.onlinebiologynotes.com/dna-replication/

DNA replication in prokaryotes

1. Initiation:

DNA replication begins from origin. In E coli, replication origin is called OriC which consists of 245 base pair and contains DNA sequences that are highly conserved among bacterial replication origin. Two types of conserved sequences are found at OriC, three repeats of 13 bp (GATRCTNTTNTTTT) and four/five repeats of 9 bp (TTATCCACA) called 13 mer and 9 mer respectively.

• About 20 molecules of Dna A proteins binds with 9 mer repeats along with ATP which causes DNA to wraps around dnaA protein forming initial complex. The dna A protein and ATP trigger the opening of 13 mer repeats froming open complex.
• Two copies of dnaB proteins (helicase) binds to 13 mer repeats. This binding is facilitated by another molecule called dnaC. The dnaB-dnaC interaction causes dnaB ring to open which binds with each of the DNA strand. The hydrolysis of bound ATP release dnaC leaving the dnaB bound to the DNA strand.
• The binding of helicase is key step in replication initiation. dnaB migrates along the single stranded DNA in 5’-3’ direction causing unwinding of the DNA.
• The activity of helicase causes the topological stress to the unwinded strand forming supercoiled DNA. This stress is relieved by the DNA topoisomerase (DNA gyrase) by negative supercoiling. Similarly, single stranded binding protein binds to th separated strand and prevents reannaeling of separated strand and stabilize the strand.
• The DNA polymerase cannot initiate DNA replication. So, at first primase synthesize 10±1 nucleotide (RNA in nature) along the 5’-3’ direction. In case of E.coli primer synthesized by primase starts with ppp-AG-nucleotide. Primer is closely associated with dnaB helicase so that it is positioned to make RNA primer as ssDNA of lagging strand. 

2. Elongation:

• i. Leading strand synthesis:

• Leading strand synthesis is more a straight forward process which begins with the synthesis of RNA primer by primase at replication origin.
• DNA polymerase III then adds the nucleotides at 3’end. The leading strand synthesis then proceed continuously keeping pace with unwinding of replication fork until it encounter the termination sequences.

 

• ii. Lagging strand synthesis:

• The lagging strand synthesized in short fragments called Okazaki fragments. At first RNA primer is synthesized by primase and as in leading strand DNA polymerase III binds to RNA primer and adds dNTPS.
• On this level the synthesis of each okazaki fragments seems straight forward but the reality is quite complex.

 

Mechanism of Lagging strand synthesis

• The complexicity lies in the co-ordination of leading and lagging strand synthesis. Both the strand are synthesized by a single DNA polymerase III dimer which accomplished the looping of template DNA of lagging strand synthesizing Okazaki fragments.
• Helicase (dnaB) and primase (dnaG) constitute a functional unit within replication complex called primosome.
• DNA pol III use one set of core sub unit (Core polymerase) to synthesize leading strand and other set of core sub unit to synthesize lagging strand.
• In elongation steps, helicasein front of primaseand pol III, unwind the DNA at the replication fork and travel along lagging strand template along 5’-3’ direction.
• DnaG primase occasionally associated with dnaB helicase synthesizes short RNA primer. A new B-sliding clamp is then positioned at the primer by B-clamp loading complex of DNA pol III.
• When the Okazaki fragments synthesis is completed, the replication halted and the core sub unit dissociates from their sliding clamps and associates with new clamp. This initiates the synthesis of new Okazaki fragments.
• Both leading and lagging strand are synthesized co-ordinately and simultaneously by a complex protein moving in 5’-3’ direction. In this way both leading and lagging strand can be replicated at same time by a complex protein that move in same direction.
• Every so often the lagging strands must dissociates from the replicosome and reposition itself so that replication can continue.
• Lagging strand synthesis is not completes until the RNA primer has been removed and the gap between adjacent Okazaki fragments are sealed. The RNA primer are removed by exonuclease activity (5’-3’) of DNA pol-I and replaced by DNA. The gap is then sealed by DNA ligase using NAD as co-factor.

 

3. Termination:

• Evantually the two replication fork of circular E. coli chromosome meet at termination recognizing sequences (ter).
• The Ter sequence of 23 bp are arranged on the chromosome to create trap that the replication fork can enter but cannot leave. Ter sequences function as binding site for TUS protein.
  

  

• Ter-TUS complex can arrest the replication fork from only one direction. Ter-TUS complex encounter first with either of the replication fork and halt it. The other opposing replication fork halted when it collide with the first one. This seems the Ter-TUS sequences is not essential for termination but it may prevents over replication by one fork if other is delayed or halted by a damage or some obstacle.
• When either of the fork encounter Ter-TUS complex, replication halted.
• Final few hundred bases of DNA between these large protein complexes are replicated by not yet known mechanism forming two interlinked (cataneted) chromosome.
• In E. coli DNA topoisomerase IV (type II) cut the two strand of one circular DNA and segrate each of the circular DNA and finally join the strand. The DNA finally transfer to two daughter cell.

A question to atheists and evolution believers:

How did the first assumed unicellular organism evolve this complex DNA replication machinery just during its short lifespan? Remember that reproduction and DNA replication are not possible if just one element is missing in this complex machinery.