Epigenetics

Epigenetics

https://reasonandscience.catsboard.com/t2098-epigenetics

Moshe Szyf: The early life environment and the epigenome 2009 Feb 3
The genome is programmed by the epigenome, which is comprised of chromatin, a covalent modification of DNA by methylation and noncoding RNAs. The epigenome is sculpted during gestation, resulting in the diversity of gene expression programs in the distinct cell types of the organism. Recent data suggest that epigenetic programming of gene expression profiles is sensitive to the early-life environment and that both the chemical and social environment early in life could affect the manner by which the genome is programmed by the epigenome.
https://pubmed.ncbi.nlm.nih.gov/19364482/

María A. Sánchez-Romero: The bacterial epigenome 14 November 2019
In all domains of life, genomes contain epigenetic information superimposed over the nucleotide sequence. Epigenetic signals control DNA–protein interactions and can cause phenotypic change in the absence of mutation. A nearly universal mechanism of epigenetic signalling is DNA methylation. In bacteria, DNA methylation has roles in genome defence, chromosome replication and segregation, nucleoid organization, cell cycle control, DNA repair and regulation of transcription. In many bacterial species, DNA methylation controls reversible switching (phase variation) of gene expression, a phenomenon that generates phenotypic cell variants. The formation of epigenetic lineages enables the adaptation of bacterial populations to harsh or changing environments and modulates the interaction of pathogens with their eukaryotic hosts.
https://www.nature.com/articles/s41579-019-0286-2

Madhumita Bhattacharyya: Origin and Evolution of DNA methyltransferases (DNMT) along the tree of life: A multi-genome survey April 09, 2020.
DNA methylation was found to play important roles in the biology of bacteria: phenomena such as timing of DNA replication, partitioning nascent chromosomes to daughter cells, repair of DNA, and timing of transposition and conjugal transfer of plasmids are sensitive to the methylation states of specific DNA regions.
https://www.biorxiv.org/content/10.1101/2020.04.09.033167v1.full

Thomas Malone: Structure-guided Analysis Reveals Nine Sequence Motifs Conserved among DNA Amino-methyltransferases, and Suggests a Catalytic Mechanism for these Enzymes 1995 Nov 3
DNA Mtases transfer methyl groups from S-adenosyl-L-methionine (AdoMet) to specific positions on bases in double-stranded DNA. The DNA Mtases fall into two major classes, defined by the position methylated. The members of one class methylate a pyrimidine ring carbon yielding C5-methylcytosine (5mC; e.g. HhaI Mtase, M.HhaI). Members of the second class methylate exocyclic amino nitrogens, forming either N6-methyladenine (N6mA; e.g. M.TaqI) or N4-methylcytosine (N4mC; e.g. M.PvuII). Mtases of the two classes were expected to be substantially different from one another, based on the fact that their targets of methyl transfer are very different
https://sci-hub.ee/10.1006/jmbi.1995.0577

Claim:  The recent discoveries of epigenetics add to the information at hand. It does not overturn it. There is still population genetics. Mutation, natural selection, genetic drift, non-random mating, and gene flow still happen and still cause population gene pools to change. Allopatric speciation and sympatric speciation still happen due to origins of reproductive-isolating mechanisms. Macroevolution and common descent still exists and still have their supporting evidences. None of that has gone away with the discovery of epigenetic inheritance.
Answer: Epigenetics shift the essential mechanisms that shape cell size and form, body architecture and form, organization and size, to mechanisms beyond Genes. This means as well, in order for form or size either on cell or organ, or organism level to change, epigenetic change has to be taken into consideration. If epigenetic informational codes change, then cells and bodies can and do change as well. This shift is considerable, and essential, and refutes gene-centric views on which the theory of evolution is based.  

Following 23 items below do define Cell, organ and organism development, size, type, architecture, and shape:

Genetic:
1.DNA Code sequence

Epigenetic ( beyond or outside the genetic information ) :

1.  The 31 Genetic Codes 
2.  The Adhesion Code
3.  The Apoptosis Code
4.  The Bioelectric Code
5.  The Biophoton Code
6.  The Calcium Code
7.  The Chaperone Code
8.  The Chromatin Code
9.  The Circular motif ( ribosome) Code
10.  The Coactivator/corepressor/epigenetic Code
11. The Code of human language
12. The Hidden Code within the Genetic Code
13. The DNA methylation Code
14. The Differentiation Code
15. The Domain substrate specificity Code of Nonribosomal peptide synthetases (NRPS)
16. The Error correcting Code
17. The Genomic regulatory Code
18. The Glycomic Code
19. The Histone Code
20. The HOX Code
21. The immune response code, or language
22. The Lamin Code
23. The MeshCODE
24. The Metabolic Code
25. The Myelin Code
26. The Neuronal spike-rate Code
27. The Non-ribosomal Code
28. The Nucleosome Code
29. The Olfactory Code
30. The Operon Code
31. The Phosphorylation Code
32. The Post-translational modification Code for transcription factors
33. The RNA Code
34. The Ribosomal Code
35. The Riboswitch Code
36. The Splicing Codes
37. The Signal transduction Code
38. The Signal Integration Codes
39. The Sugar Code
40. The Synaptic Adhesive Code
41. The Talin Code
42. The Transcription factor Code
43. The Transcriptional cis-regulatory Code
44. The Tubulin Code
45. The Ubiquitin Code



There is just ONE item which is genetic, namely the genetic DNA sequence, which upon population genetics. Mutation, natural selection, genetic drift, non-random mating, and gene flow cause population gene pools to change. Allopatric speciation and sympatric speciation still happen due to origins of reproductive-isolating mechanisms. But these mechanisms on a genetic level have influence in a VERY limited range.

Where Do Complex Organisms Come From?
https://reasonandscience.catsboard.com/t2316-where-do-complex-organisms-come-from

The argument of the genetic piano
1. Dr. Kohzoh Mitsuya [University of Texas Health Science Center] who studies genes says the work of epigenetics “corresponds to a pianist playing a piece of music. Like keys on a piano, DNA is the static blueprint for all the proteins that cells produce.”
2. “Epigenetic information provides additional dynamic or flexible instructions as to how, where and when the blueprint will be used.”
3. After watching the response of mice deficient in the RNA, he said, “It shows how one note is played on the piano. The symphony has only just come into view. We can hear it, but we need to learn how all the parts are being played.”
4. Here the questions are: who’s the pianist and who’s the conductor? 
5. The environment cannot be the musician; it is oblivious to the needs of the organism.  Heredity cannot be the musician; it has no foresight to read or comprehend a collection of processes organized into a work.
6. Thus, this discovery and explanation of Dr. Mitsuya causes trouble for Darwin while it fits precisely into the intelligent design theory.
7. There must be an origin of the information required to produce function.
8. A classical answer to this by the evolutionists is: “this evolved, that’s why it is there.”
9. Answering this we say: “Science is supposed to seek efficient causes, not just-so stories or appeals to chance based on circular reasoning. For example, in his book The Making of the Fittest, Sean Carroll writes “the degree of similarity in DNA is an index of the [evolutionary] relatedness of species.” [98] This can only make sense if we first assume evolution is true. But Carroll’s book is a defense of evolution, intended to demonstrate that the theory is true without first assuming it is true. He seeks to prove evolution is true, but he begins with evolutionary reasoning and interpretations. That is circular reasoning.”
10. The alternative and only explanation is therefore intelligent design with a known cause sufficient to produce functional information: intelligence. Only intelligence can organize atoms or building blocks into order and activities. There is no other experience of anything else putting things into order and motion.
11. Intelligent design means intelligence of the greatest scientist all men call God.
12. A Creator, most probably, is required, and exists.

Reference:
1.  Watanabe, Tomizami, Mitsuya et al, “Role for piRNAs and Noncoding RNA in de Novo DNA Methylation of the Imprinted Mouse Rasgrf1 Locus,” Science, 13 May 2011: Vol. 332 no. 6031 pp. 848-852, DOI: 10.1126/science.1203919.

Humans have only 21,000 genes—the same as a worm—and they are identical in all of the different types of cells. It is not the inherited code of the genes that determines the different cellular functions. Rather, it is way that genes are utilized differently in each type of cell that determines which proteins will produce unique structures. 6

Increasingly, these “epigenetic” mechanisms (that is, mechanisms outside of the simple procedure of assigning an amino acid directly from a code in a gene) are being found to be vastly more complex than ever imagined. This post will describe recent discoveries of dynamic three-dimensional structures in the cell’s nucleus that along with unique localization and packaging of the DNA are vital for every aspect of gene function. Vast complexity of chromatin 3D shapes is another way that DNA is regulated.

Stephen C Meyer , Darwin's doubt pg.218:

Contemporary critics of neo-Darwinism acknowledge, of course, that preexisting forms of life can diversify under the twin influences of natural selection and genetic mutation. Known microevolutionary processes can account for small changes in the coloring of peppered moths, the  acquisition of antibiotic resistance in different strains of bacteria, and cyclical variations in the size of Galápagos finch beaks. Nevertheless, many biologists now argue that neo-Darwinian theory does not provide an adequate explanation for the origin of new body plans or events such as the Cambrian explosion. For example, evolutionary biologist Keith Stewart Thomson, formerly of Yale University, has expressed doubt that large-scale morphological changes could accumulate by minor changes at the genetic level. Geneticist George Miklos, of the Australian National University, has argued that neo- Darwinism fails to provide a mechanism that can produce large-scale innovations in form and structure. Biologists Scott Gilbert, John Opitz, and Rudolf Raff have attempted to develop a new theory of evolution to supplement classical neo-Darwinism, which, they argue, cannot adequately explain large-scale macroevolutionary change. As they note:

Starting in the 1970s, many biologists began questioning its neo-Darwinism's adequacy in explaining evolution. Genetics might be adequate for explaining microevolution, but  microevolutionary changes in gene frequency were not seen as able to turn a reptile into a mammal or to convert a fish into an amphibian. Microevolution looks at adaptations that concern the survival of the fittest, not the arrival of the fittest. As Goodwin (1995) points out, "the origin of species—Darwin's problem—remains unsolved."

pg. 204

Genes alone do not determine the three-dimensional form and structure of an animal. so-called epigenetic information—information stored in cell structures, but not in DNA sequences—plays a crucial role. The Greek prefix epi means "above" or "beyond," so epigenetics refers to a source of information that lies beyond the genes. "Detailed information at the level of the gene does not serve to explain form." "epigenetic" or "contextual information" plays a crucial role in the formation of animal "body  assemblies" during embryological development.

Recent discoveries about the role of epigenetic information in animal development pose a formidable challenge to the standard neo-Darwinian account of the origin of these body plans—perhaps the most formidable of all. "the neo-Darwinian paradigm still represents the central explanatory framework of evolution," it has "no theory of the generative." neo-Darwinism "completely avoids the question of the origination of phenotypic traits and of organismal form." 1

Neo-Darwinism lacks an explanation for the origin of organismal form precisely because it cannot explain the origin of epigenetic information.


FORM AND INFORMATION

Biologists typically define "form" as a distinctive shape and arrangement of body parts. Forms exist in three spatial dimensions and arise in time—in the case of animals during development from embryo to adult. Animal form arises as material constituents are constrained to establish specific arrangements with an identifiable three-dimensional shape , one that we would recognize as the body plan of a particular type of animal. A particular "form," therefore, represents a highly specific arrangement of material components among a much larger set of possible arrangements.

Similarly, animal body plans represent, not only highly improbable, but also highly specific arrangements of matter. Organismal form and function depend upon the precise arrangement of various constituents as they arise during, or contribute to, embryological development. Thus, the specific arrangement of the other building blocks of biological form—cells, clusters of similar cell types,  tissues, and organs—also represent a kind of specified or functional information.

Neo-Darwinists have assumed that genes possess all the information necessary to specify the form of an animal. They have also assumed that mutations in genes will suffice to generate the new information necessary to build a new form of animal life. 2


BEYOND GENES

Many biologists no longer believe that DNA directs virtually everything happening within the cell. Developmental biologists, in particular, are now discovering more and more ways that crucial information for building body plans is imparted by the form and structure of embryonic cells, including information from both the unfertilized and fertilized egg.  Biologists now refer to these sources of information as "epigenetic." The information needed to code for complex biological systems vastly outstrips the information in DNA. 3

Once proteins are synthesized, they must be arranged into higher-level systems of proteins and structures.

Distinctive cell types are made of, among other things, systems of specialized proteins. Organs are made of specialized arrangements of cell types and tissues. And body plans comprise specific arrangements of specialized organs. Yet the properties of individual proteins do not fully determine the organization of these higher-level structures and patterns. 4

CYTOSKELETAL ARRAYS

Other sources of information must help arrange individual proteins into systems of proteins, systems of proteins into distinctive cell types, cell types into tissues, and different tissues into organs. And different organs and tissues must be arranged to form body plans.

At a construction site, builders will make use of many materials: lumber, wires, nails, drywall, piping, and windows. Yet building materials do not determine the floor plan of the house or the arrangement of houses in a neighborhood. Similarly, electronic circuits are composed of many components, such as resistors, capacitors, and transistors. But such lower-level components do not determine their own arrangement in an integrated circuit

In a similar way, DNA does not by itself direct how individual proteins are assembled into these larger systems or structures—cell types, tissues, organs, and body plans—during animal development.Instead, the three-dimensional structure or spatial architecture of embryonic cells  plays important roles in determining body-plan formation during embryogenesis. Developmental biologists have identified several sources of epigenetic information in these cells.

The structure and location of the microtubules in the cytoskeleton influence the patterning and development of embryos. Microtubule "arrays" within embryonic cells help to distribute essential proteins used during development to specific locations in these cells. Once delivered, these proteins perform functions critical to development, but they can only do so if they are delivered to their correct locations with the help of preexisting, precisely structured microtubule or cytoskeletal arrays.

Thus, the precise arrangement of microtubules in the cytoskeleton constitutes a form of critical structural information. These microtubule arrays are made of proteins called tubulin, which are gene products. Nevertheless, like bricks that can be used to assemble many different structures, the tubulin proteins in the cell's microtubules are identical to one another. Thus, neither the tubulin subunits, nor the genes that produce them, account for the differences in the shape of the microtubule arrays that distinguish different kinds of embryos and developmental pathways. Instead, the structure of the microtubule array itself is, once again, determined by the location and arrangement of its subunits, not the properties of the subunits themselves.

The Centrosome

https://www.youtube.com/watch?v=5rqbmLiSkpk

Another cell structure influences the arrangement of the microtubule arrays and thus the precise structures they form and the functions they perform. In an animal cell, that structure is called the centrosome (literally, "central body"), a microscopic organelle that sits next to the nucleus between cell divisions in an undividing cell. Emanating from the centrosome is the microtubule array that gives a cell its three-dimensional shape and provides internal tracks for the directed transport of  organelles and essential molecules to and from the nucleus. During cell division the centrosome duplicates itself. The two centrosomes form the poles of the cell-division apparatus, and each daughter cell inherits one of the centrosomes; yet the centrosome contains no DNA. Though  centrosomes are made of proteins—gene products—the centrosome structure is not determined by genes alone.

pg 213:

NEO-DARWINISM AND THE CHALLENGE OF EPIGENETIC INFORMATION

These different sources of epigenetic information in embryonic cells pose an enormous challenge to  the sufficiency of the neo-Darwinian mechanism. According to neo-Darwinism, new information, form, and structure arise from natural selection acting on random mutations arising at a very low level within the biological hierarchy—within the genetic text. Yet both body-plan formation during embryological development and major morphological innovation during the history of life depend upon a specificity of arrangement at a much higher level of the organizational hierarchy, a level that DNA alone does not determine. If DNA isn't wholly responsible for the way an embryo develops— for body-plan morphogenesis—then DNA sequences can mutate indefinitely and still not produce a new body plan, regardless of the amount of time and the number of mutational trials available to the evolutionary process. Genetic mutations are simply the wrong tool for the job at hand.

Even in a best-case scenario—one that ignores the immense improbability of generating new genes by mutation and selection—mutations in DNA sequence would merely produce new genetic information. But building a new body plan requires more than just genetic information. It requires both genetic and epigenetic information—information by definition that is not stored in DNA and thus cannot be generated by mutations to the DNA. It follows that the mechanism of natural selection acting on random mutations in DNA cannot by itself generate novel body plans, such as those that first arose in the Cambrian explosion.  

In at least the case of the sugar molecules on the cell surface, gene products play no direct role. Genetic information produces proteins and RNA molecules, not sugars and carbohydrates. Of course, important glycoproteins and glycolipids (sugar-protein and sugar-fat composite molecules) are modified as the result of biosynthetic pathways involving networks of proteins. Nevertheless, the genetic information that generates the proteins in these pathways only determines the function and structure of the individual proteins; it does not specify the coordinated interaction between the  proteins in the pathways that result in the modification of sugars

Some biologists have noted that so-called helper proteins—which are gene products—called "microtubule associated proteins" (MAPs) help to assemble the tubulin subunits in the microtubule arrays. Yet MAPs, and indeed many other necessary proteins, are only part of the story. The locations of specified target sites on the interior of the cell membrane also help to determine the shape of the cytoskeleton. And, as noted, the gene products out of which these targets are made do not determine the location of these targets. Similarly, the position and structure of the centrosome—the microtubule- organizing center—also influences the structure of the cytoskeleton. Although centrosomes are made of proteins, the proteins that form these structures do not entirely determine their location and form.

As Mark McNiven, a molecular biologist at the Mayo Clinic, and cell biologist Keith Porter, formerly of the University of Colorado, have shown, centrosome structure and membrane patterns as a whole convey three-dimensional structural information that helps determine the structure of the cytoskeleton and the location of its subunits.

In each new generation, the form and structure of the cell arises as the result of both gene products and the preexisting three-dimensional structure and organization inherent in cells, cell membranes, and cyto-skeletons. Many cellular structures are built from proteins, but proteins find their way to correct locations in part because of preexisting three-dimensional patterns and organization inherent in cellular structures. Neither structural proteins nor the genes that code for them can alone determine the three-dimensional shape and structure of the entities they build. Gene products provide necessary, but not sufficient, conditions for the development of three-dimensional  structure within cells, organs, and body plans. 5 If this is so, then natural selection acting on genetic  variation and mutations alone cannot produce the new forms that arise in the history of life.

The structures in which epigenetic information inheres—cytoskeletal arrays and membrane patterns, for example—are much larger than individual nucleotide bases or even stretches of DNA. For this reason, these structures are not vulnerable to alteration by many of the typical sources of mutation that affect genes such as radiation and chemical agent. To the extent that cell structures can be altered, these alterations are overwhelmingly likely to have harmful or catastrophic consequences.


1) Müller and Newman, "Origination of Organismal Form,"  Or as Müller also explains, the
question of how "individualized constructional elements" are organized during "the evolution of
organismal form" is "not satisfactorily answered by current evolutionary theories"; Müller, "Homology," 57-58
2) Levinton, Genetics, Paleontology, and Macroevolution, 485
3) Goodwin, "What Are the Causes of Morphogenesis?"; Nijhout, "Metaphors and the Role of Genes in Development"; Sapp, Beyond the Gene; Müller and Newman, "Origination of Organismal Form"; Brenner, "The Genetics of Behaviour"; Harold, The Way of the Cell.
4) Harold, The Way of the Cell, 125.
5) Harold, "From Morphogenes to Morphogenesis," 2767

http://www.microbiologyresearch.org/docserver/fulltext/micro/141/11/mic-141-11-2765.pdf expires=1475512019&id=id&accname=guest&checksum=82B036E71F67093D4C4B4F076E6D8114

Harold, “From Morphogenes to Morphogenesis,” 2774; Moss, What Genes Can’t Do. Of course, many proteins bind chemically with each other to form complexes and structures within cells. Nevertheless, these “self-organizational” properties do not fully account for higher levels of organization in cells, organs, or body plans. Or, as Moss has explained “Neither DNA nor any other aperiodic crystal constitutes a unique repository of heritable stability in the cell; in addition, the chemistry of the solid state does not constitute either a unique or even an ontologically or causally privileged basis for explaining the existence and continuity of order in the living world . . .” Moss, What Genes Can’t Do, 76.

Morphogenesis cannot be orchestrated by the genome, but makes manifest a higher level of order, corresponding to the cellular scale of size and organization. If a single phrase can stand for the whole riddle, it may be ‘ cell polarity ’, The term refers to the visible directionality

6) http://jonlieffmd.com/blog/vast-complexity-of-chromatin-3d-shapes

Epigenomics: the epigenome is a genome-wide map of reversible chemical modifications to DNA and its associated proteins that determine when genes can be expressed. "By 2004, large-scale genome projects were already indicating that genome sequences, within and across species, were too similar to be able to explain the diversity of life. It was instead clear that epigenetics - those changes to gene expression caused by chemical modification of DNA and its associated proteins - could explain much about how these similar genetic codes are expressed uniquely in different cells, in different environmental conditions and at different times." "Epigenetic coding will be orders of magnitude more complex than genetic coding". (Nature 4 Feb 2010). "The human genome is singular and finite, but the human epigenome is almost infinite - the epigenome changes in different states and different tissues". Every cell in our body has its own epigenome, that is 10¹⁵ different epigenomes (Marianne Rots). 1

1) http://wasdarwinwrong.com/kortho44.htm

Stephen C Meyer , Darwin's doubt pg.268:

THE HIERARCHICAL ORGANIZATION OF GENETIC AND EPIGENETIC  INFORMATION

In addition to the information stored in individual genes and the information present in the integrated  networks of genes and proteins in dGRNs, animal forms exemplify hierarchical arrangements or layers of information-rich molecules, systems, and structures. For example, developing embryos require epigenetic information in the form of specifically arranged

(a) membrane targets and patterns,
(b) cytoskeletal arrays,
(c) ion channels, and
(d) sugar molecules on the exterior of cells (the sugar code).

Much of this epigenetic information resides in the structure of the maternal egg and is inherited directly from membrane to membrane independently of DNA.  This three-dimensional structural information interacts with other information-rich molecules and systems of molecules to ensure the proper development of an animal. In particular, epigenetic information influences the proper positioning and thus the function of regulatory proteins (including  DNA-binding proteins), messenger RNAs, and various membrane components. Epigenetic information also influences the function of developmental gene regulatory networks. Thus, information at a higher structural level in the maternal egg helps to determine the function of both whole networks of genes and proteins (dGRNs) and individual molecules (gene products) at a lower level within a developing animal. Genetic information is necessary to specify the arrangement of amino acids in a protein or bases in an RNA molecule. Similarly, dGRNs are necessary to specify the location and/or function of many gene products. And, in a similar way, epigenetic information is necessary to specify the location and determine the function of lower-level molecules and systems of molecules, including the dGRNs themselves.  Furthermore, the role of epigenetic information provides just one of many examples of the hierarchical arrangement (or layering) of information-rich structures, systems, and molecules within animals. Indeed, at every level of the biological hierarchy, organisms require specified and highly improbable (information-rich) arrangements of lower-level constituents in order to maintain their form and function. Genes require specified arrangements of nucleotide bases; proteins require specified arrangements of amino acids; cell structures and cell types require specified arrangements of proteins or systems of proteins; tissues and organs require specific arrangements of specific cell types; and body plans require specialized arrangements of tissues and organs. Animal forms contain information-rich lower-level components (such as proteins and genes). But they also contain information-rich arrangements of those components (such as the arrangement of genes and gene products in dGRNs or proteins in cytoskeletal arrays or membrane targets). Finally, animals also exhibit information-rich arrangements of higher-level systems and structures (such as the arrangements of specific cell types, tissues, and organs that form specific body plans).

The highly specified, tightly integrated, hierarchical arrangements of molecular components and systems within animal body plans also suggest intelligent design. This is, again, because of our experience with the features and systems that intelligent agents—and only intelligent agents— produce. Indeed, based on our experience, we know that intelligent human agents have the capacity to generate complex and functionally specified arrangements of matter—that is, to generate specified complexity or specified information. Further, human agents often design information-rich hierarchies, in which both individual modules and the arrangement of those modules exhibit complexity and specificity—specified information. Individual transistors, resistors, and capacitors in an integrated circuit exhibit considerable complexity and specificity of design. Yet at a higher level of organization, the specific arrangement and connection of these components within an integrated circuit requires additional information and reflects further design (see Fig.below).



Conscious and rational agents have, as part of their powers of purposive intelligence, the capacity to design information-rich parts and to organize those parts into functional information-rich systems and hierarchies. We know of no other causal entity or process that has this capacity. Clearly, we have good reason to doubt that mutation and selection, self-organizational processes, or any of the other undirected processes cited by other materialistic evolutionary theories, can do so. Thus, based upon our present experience of the causal powers of various entities and a careful assessment of the efficacy of various evolutionary mechanisms, we can infer intelligent design as the best explanation for the origin of the hierarchically organized layers of information needed to build the animal forms that arose in the Cambrian period.

There is another remarkable aspect of the hierarchical organization of information in animal forms.  Many of the same genes and proteins play very different roles, depending upon the larger organismal  and informational context in which they find themselves in different animal groups. For example, the  same gene (Pax-6 or its homolog, called eyeless), helps to regulate the development of the eyes of fruit flies (arthropods) and those of squid and mice (cephalopods and vertebrates, respectively). Yet arthropod eyes exemplify a completely different structure from vertebrate or cephalopod eyes. The fruit fly possesses a compound eye with hundreds of separate lenses (ommatidia), whereas both mice and squid employ a camera-type eye with a single lens and retinal surface. In addition, although the eyes of squid and mice resemble each other optically (single lens, large internal chamber, single retinal surface), they focus differently. They undergo completely different patterns of development and utilize different internal structures and nerve connections to the visual centers of the brain. Yet the Pax-6 gene and its homologs play a key role in regulating the construction of all three of these different adult sensory structures. Moreover, evolutionary and developmental biologists have found that this pattern of "same genes, different anatomy" recurs throughout the bilaterian phyla, for features  as fundamental as appendages, segmentation, the gut, heart, and sense organs




This pattern contradicts the expectations of textbook evolutionary theory. Neo-Darwinism predicts that disparate adult structures should be produced by different genes. This prediction follows directly from the neo-Darwinian assumption that all evolutionary (including anatomical) transformations begin with mutations in DNA sequences—mutations that are fixed in populations by natural selection, genetic drift, or other evolutionary processes. The arrow of causality flows one way from genes (DNA) to development to adult anatomy. Thus, if biologists observe different animal forms, it follows that they should expect that different genes will specify those forms during animal development. Given the profound differences between the fruit-fly compound eye and the vertebrate camera eye, neo-Darwinian theory would not predict that the "same" genes would be involved in building different eyes in arthropods and chordates.

RNA-mediated epigenetic regulation of gene expression

Diverse classes of RNA, ranging from small to long non-coding RNAs, have emerged as key regulators of gene expression, genome stability and defence against foreign genetic elements. Small RNAs modify chromatin structure and silence transcription by guiding Argonaute-containing complexes to complementary nascent RNA scaffolds and then mediating the recruitment of histone and DNA methyltransferases. In addition, recent advances suggest that chromatin-associated long non-coding RNA scaffolds also recruit chromatin-modifying complexes independently of small RNAs. These co-transcriptional silencing mechanisms form powerful RNA surveillance systems that detect and silence inappropriate transcription events, and provide a memory of these events via self-reinforcing epigenetic loops.

http://www.nature.com/nrg/journal/v16/n2/full/nrg3863.html

New Epigenetic Modification is Revealed, Major Scientific Breakthrough 1

A New Epigenetic Modification Has Been Revealed that Could Open Up the Field of Epigenetics, Says Research Team from the University of Cambridge
Epigenetic modification research keeps gaining momentum as the revolutionary science is quickly becoming one of the most important fields of research to describe our genetic expressions. But, before we discuss the most recent breakthrough in epigenetic research, we must first set the table for you. So, hang in there and I promise you, it will be well worth it.

DNA Methylation and Histone Modification
The studying of histones that bind to DNA has the primary focus of epigenetic modification research. These histones can be modified, which can result in genes being read or not. There are basically 5 different types of Histone proteins called H2A,H2B, H3 and H4 which form a bead on which the DNA is wrapped (with two molecules each, so a total 8 protein molecules in the bead and one called H1 between two beads). Within the histones, it is actually the amino acids that are modified.

In addition to histone modifications, genes are also known to be regulated by a form of epigenetic modification that directly affects one base of the DNA, namely the base C. This process is referred to as DNA Methylation.

The four bases are namely Adenine, Thymine, Guanine ad Cytosine. It has already been more than 60 years now, since scientists discovered that C can be modified directly. This process is executed as small molecules of carbon and hydrogen bind to this base and allow certain genes to be turned on and off, or to ‘dim’ their activity. It is estimated that roughly 75 million, or one in ten, of the Cs in the human genome are methylated. [1]

However, published on December 21st, 2015 in the journal Nature Structural and Molecular Biology, a major new discovery suggests there exists many more DNA modifications that we did not know about.

Epigenetic Modification – Direct Methylation of the Base A
Discovered by Magdalena J Koziol, Charles R Bradshaw, George E Allen, Ana S H Costa, Christian Frezza, & John B Gurdon at the Wellcome Trust-Cancer Research UK Gurdon Institute and the Medical Research Council Cancer Unit at the University of Cambridge have identified and characterized a new form of direct modification – methylation of the base A – in several species, including frogs, mouse and humans. [2] [3]

Although, methylation of A appears to be far less common that C methylation, occurring on around 1,700, the research team urges that they are very important and spread across the entire genome. Although, it does not seem to occur on sections of our genes known as exons, which provide the code for proteins.

Opening Up the Field of Epigenetics
“These newly-discovered modifiers only seem to appear in low abundance across the genome, but that does not necessarily mean they are unimportant,” says Dr Magdalena Koziol from the Gurdon Institute. “At the moment, we don’t know exactly what they actually do, but it could be that even in small numbers they have a big impact on our DNA, gene regulation and ultimately human health.”

“It’s possible that we struck lucky with this modifier,” says Dr Koziol, “but we believe it is more likely that there are many more modifications that directly regulate our DNA. This could open up the field of epigenetics.”

The field of epigenetic is growing rapidly and has the potential to redefine our interactions with nature and each other. Stay tuned for follow up articles that will explore these findings in greater depth.

That finding helped us to understand the role of RNA methylation. Adenosine methylation is also used widely in bacterial genome.
http://epigenie.com/key-epigenetic-players/important-dna-methylation-factors/n6-methyladenosine-m6a/

m6A RNA Methylation Is Regulated by MicroRNAs and Promotes Reprogramming to Pluripotency
http://www.cell.com/cell-stem-cell/abstract/S1934-5909(15)00017-X


1. http://conceptualrevolutions.com/2015/12/26/epigenetic-modification-revealed-major-scientific-breakthrough/

Epigenetics and Cellular Metabolism

Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038610/

Epigenetics encompasses a series of nongenetic processes, ranging from nongenetic mechanisms of gene expression to deposition of cytoplasmic factors in gametes, mechanisms of developmental plasticity, transgenerational plasticity, and evolutionary change (including the speciation process), all of which involve no changes in genes or genetic information in general. It comprises the generation of epigenetic information (parental cytoplasmic factors) and its role in gametogenesis, gene imprinting, as well as the crucial role of parental cytoplasmic factors in activating expression of zygotic genes, determining the early individual development; it deals with the role of the postphylotypic nervous system in activation of nonhousekeeping genes and GRNs, cell differentiation, organogenesis, and morphogenesis in the process of individual development as well as the maintenance of homeostasis.

To put it more explicitly, epigenetic processes direct (control and regulate) individual development and reproduction, which is another way of saying that epigenetic processes determine the inheritance at the supracellular level that is manifested in the visible metazoan phenotype (morphology, physiology, behavior, and life history). This statement implies the existence of an epigenetic system of heredity, predicted by Maynard Smith.

The genetic piano
1. The work of the gene regulatory network “corresponds to a pianist playing a piece of music. Like keys on a piano, DNA is the blueprint to make the proteins that cells require. Epigenetic information provides dynamic, flexible instructions as to how, where, and when the information stored in DNA will be expressed.
2.  There must be an origin of the information required to produce function. Who’s the pianist and who’s the conductor?  The environment cannot be the director. Heredity cannot be the musician; it has no foresight to orchestrate the collection of processes organized into a meaningful, functional outcome.
3. Science is supposed to seek efficient and adequate causes, not just-so stories, or appeals to chance based on circular reasoning.  The alternative and the only explanation is therefore intelligent design with a known cause sufficient to produce functional instructional information: an intelligent agent.

Conscious and rational agents have, as part of their powers of purposive intelligence, the capacity to design information-rich parts and to organize those parts into functional information-rich systems and hierarchies. We know of no other causal entity or process that has this capacity. Clearly, we have good reason to doubt that mutation and selection, self-organizational processes, or any of the other undirected processes cited by other materialistic evolutionary theories, can do so. Thus, based upon our present experience of the causal powers of various entities and a careful assessment of the efficacy of various evolutionary mechanisms, we can infer intelligent design as the best explanation for the origin of the hierarchically organized layers of information needed to build the variety of animal forms.

1. Complex multicellular lifeforms depend on gene regulatory networks (dGRN's) which are a collection of molecular regulators that interact with each other and with other substances in the cell to orchestrate the expression of DNA.
2. dGRN's operate based on logic gates and their networks process chemical input signals similar to computers. These encoded instructions are based on boolean logic.
3. Logic depends on reason. Reason depends on intelligence. Only an intelligent mind can think rationally, and implement a system based on conceptual laws of logic. Therefore, the best and most reasonable explanation for the existence of complex gene regulatory networks based on boolean logic, essential for the make of complex multicellular organisms, is the creative action of a powerful, transcendent, intelligent Creator.

1. Regulating, governing, controlling, recruiting, interpreting, recognising, orchestrating, choreographing, elaborating strategies, guiding, instructing, fine-tuning, monitoring, organizing, are all tasks of the gene regulatory network, which are ultrasophisticated communication networks, analogous to electric circuits in man-made devices.
2. In the same sense as copper, plastic, basic electronic parts do not turn into a  printed circuit board randomly, molecular regulators, transcription factors, on/off switches, feedback loops do not turn into a gene regulatory network by unguided processes. Communication networks and signal transmission systems, similar as seen in gene regulatory networks, highly flexible, and able to rapidly reconfigure to deliver different outputs can only be implemented and pre-programmed by intelligence.
3. Therefore, most probably, the gene regulatory network was implemented and programmed by an intelligent agency.

The Mysterious Epigenome. What lies beyond DNA.
https://www.youtube.com/watch?v=RpXs8uShFMo

Every day scientists learn more about the regulation of gene expres​sion(gene activity). Your genome is like a huge piano keyboard that contains more than 20,000 keys; each gene in your genome is like a key in this huge keyboard. Science is proving that what you experience throughout your life changes the way your genes operate. Your genes and your lifestyle form a feedback loop, and what you do to your genes makes a big difference.

Your lifestyle changes the expression of your genes through epigenetic marks or epigenes; these marks change gene expression without changing the DNA sequence itself. Several mechanisms are employed in epigenetic marking, including DNA methylation of CpG islands, post-translational modifications of histones, and non-coding RNA (ncRNA). In fact, epigenetic programming is different in every cell type in the human body; different genes are expressed in different cell types.

The term epigenome indicates all those epigenetic marks that are added onto our genes to control the expression of our genes. The epigenome is nearly indistinguishable at birth in identical twins, but it diverges as they age. This explains why one twin may be more susceptible to a certain disease than the other although DNA sequences are the same in identical twins.

Like piano keys that produce inimitable sounds in response to external stimuli (fingering), genes produce inimitable expressions in response to their intricate genetic programming, and also in response to the different external stimuli that exist in life. Genes are switched on and off through some epigenetic marks that are largely dependent on life experiences; that is, on what happened to the genes throughout life. The epigenetic marks are allowing those lifestyle choices that we make to be traced to the genome, and are the equivalent of the fingering scheme for a piano keyboard.

Epigenetic modifiers are diverse, including diet, smoking, alcohol consumption, exercise, emotions, and even prayers. A recent study on rats showed that a diet rich in fructose disrupted the epigenetic control of more than 200 genes that are normally expressed in the hippocampus. The hippocampus regulates the processes of learning and memory, and therefore, fructose-rich diet impaired memory in rats. Fortunately, the harmful effect of fructose on brain genes could be reversed by a diet rich in Omega-3 fatty acid.

Emotions also act as epigenetic modifiers and can mark brain genes that are involved in stress responses. In experiments with rats, researchers found that rats raised by attentive mothers were able to deal with stressful situations better than rats raised by negligent mothers. The epigenetic marks of the genes normally expressed in the brain were different between the two rat groups. In humans, the stress-dampening genes are epigenetically turned-off in the brains of adults who suffered from unhappy childhood experiences. Emotional disturbances as panic, Post-Traumatic Stress Disorder (PTSD), and schizophrenia can alter gene expression in the brain through epigenetic marks that are grossly different from those marks found in normal happy individuals.

Inappropriate epigenetic marks could be responsible for a new class of diseases; epigenetic diseases. In human atherosclerosis, certain genes are turned off by hypermethylation—epigenetic marks—and gene expression is epigenetically shifted in endothelial cells from atheroprotective to pro-atherogenic status. Epigenetic diseases include also Type II Diabetes and obesity.

The gene encoding leptin—a hormone that inhibits hunger and regulates body weight—is also under epigenetic control. Many tumor suppressor genes are silenced by epigenetic marks that methylate the CpG islands in the promoters of these genes. Epigenetic therapy will be available in the near future to target those silenced tumor suppressor genes. This approach could weaken the cancer cell to the extent that it will be killed by lower doses of chemotherapeutic agents.

Not only does your lifestyle determine the activities of your genes, it also changes the activities of the genes of your descendants. For example, the age at which a boy begins smoking cigarettes is positively related to his future son’s Body Mass Index (BMI). In another study, babies of mothers who were exposed to the World Trade Center (WTC) attacks during pregnancy, showed symptoms of PTSD early in life. These trans-generational effects are possible because some epigenetic marks can be transmitted across generations. Future fathers and mothers should, therefore, protect their epigenomes for the sake of their children and their grandchildren.

1. https://www.bibalex.org/SCIplanet/en/Article/Details?id=10288