Orphan genes are the hard problem for evolutionary genomics

Challenging LUCA: A Critical Examination of Evolutionary Claims

The theory of a Last Universal Common Ancestor (LUCA) posits that all life on Earth shares a single, ancient origin. This concept forms a cornerstone of modern evolutionary theory. However, several lines of evidence challenge the notion of a singular, linear progression of life from a common ancestor. Specifically, the C-value paradox, the existence of orphan genes, and the nature of pseudogenes collectively undermine the simplicity and plausibility of the LUCA hypothesis.

The C-Value Paradox

One of the most perplexing challenges to the LUCA concept is the C-value paradox, which describes the lack of correlation between an organism’s genome size (C-value) and its perceived complexity. If all life descended from a common ancestor, one would expect a more straightforward relationship between genome size and organismal complexity. Yet, this is not observed. For instance, the human genome contains approximately 3 billion base pairs, while the genome of the amoeba Amoeba dubia exceeds 600 billion base pairs, despite the amoeba being a single-celled organism.

This paradox suggests that genome size is influenced by factors other than just the accumulation of beneficial mutations. The presence of large amounts of non-coding DNA, repetitive sequences, and other genomic elements that do not contribute directly to organismal complexity indicates that genome evolution is driven by complex mechanisms beyond natural selection. This complexity is inconsistent with the gradual, stepwise progression expected from a LUCA-based evolutionary model.

Orphan Genes

Orphan genes, also known as de novo genes, present another significant challenge to the LUCA hypothesis. These genes lack recognizable homologs in other species and appear to be unique to particular lineages. Their sudden appearance without any apparent ancestral sequence contradicts the gradualist narrative of evolutionary theory.

For example, a study on fruit flies (Drosophila) identified numerous orphan genes that are species-specific and do not show any similarity to genes in closely related species. These genes often play crucial roles in the unique biological functions and adaptations of the organisms that possess them. The existence of orphan genes suggests the presence of mechanisms capable of generating entirely new genetic sequences independently of common descent, which aligns more closely with an intelligent design and Creation perspective than with the slow, incremental changes posited by LUCA.

https://communities.springernature.com/posts/the-evolutionary-mystery-of-orphan-genes

"Orphan genes are "the hard problem" for evolutionary genomics. Because we can't find other genes similar to them in other species, we can't build family trees for them. We cannot hypothesise their gradual evolution; instead they seem to appear out of nowhere. Various attempts have been made at explaining their origins but – as Paul and I describe in our book chapter – the problem remains unsolved.

Give their ubiquity in all genome sequences orphan genes receive comparatively little attention from the research community. I suspect this is partly because they are such a difficult problem. Science is "the art of the soluble". It may be that little funding finds its way to the origin of orphan genes because it appears to be an insoluble problem."

Pseudogenes

Pseudogenes, or non-functional sequences resembling functional genes, have traditionally been cited as evidence for common ancestry due to their presumed role as evolutionary relics. However, recent research has revealed that many pseudogenes are not merely "junk" DNA but have regulatory functions, influencing the expression of other genes and playing roles in genetic networks.

For instance, some pseudogenes are involved in gene regulation during development, acting as decoys for regulatory molecules or producing non-coding RNAs that influence gene expression. This functional versatility indicates that pseudogenes are integral components of the genome, not vestigial remnants of an evolutionary past. Their existence and function challenge the idea that genomes are solely shaped by random mutations and natural selection from a common ancestor.

The Role of CpG Islands

CpG islands are regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases. These regions are crucial for gene regulation. However, the methylation of cytosines within CpG sites can lead to their deamination and conversion into thymine, causing mutations. Over time, this process can lead to the depletion of CpG islands. Importantly, cells lack a mechanism to regenerate CpG islands once they are lost, making this a one-way path to degradation. This inevitable breakdown challenges the idea that complex genomes can be maintained through natural processes alone, casting further doubt on the LUCA hypothesis.

Alternative Explanations and Intelligent Design

The intricate mechanisms governing genome size, the emergence of orphan genes, the functional complexity of pseudogenes, and the degradation of CpG islands suggest a level of complexity that is difficult to reconcile with the LUCA model. Instead, these observations are more consistent with the idea of an intelligent design, where genomes are seen as dynamic, information-rich systems capable of rapid adaptation and innovation.

Moreover, the presence of sophisticated genetic mechanisms that can compensate for gene loss or alter gene expression patterns underscores the notion of a designed adaptability in living organisms. For example, alternative splicing mechanisms enable cells to produce multiple protein variants from a single gene, demonstrating an inherent flexibility and robustness in the genetic code that surpasses simple evolutionary explanations.

Conclusion

While the concept of a Last Universal Common Ancestor remains a central tenet of evolutionary theory, numerous empirical observations challenge its validity. The C-value paradox, orphan genes, the functional complexity of pseudogenes, and the inevitable breakdown of CpG islands suggest a more intricate and intelligently orchestrated biological landscape. These findings invite a reconsideration of the origins and mechanisms of life, emphasizing the need for alternative frameworks that account for the observed genetic diversity and complexity.

There is no mechanism for evolution. Observed science points to Intelligent Design and Creation.

References

1. Gregory, T. R. (2005). The C-value enigma in plants and animals: a review of parallels and an appeal for partnership. Annals of Botany, 95(1), 133-146.
2. Tautz, D., & Domazet-Lošo, T. (2011). The evolutionary origin of orphan genes. Nature Reviews Genetics, 12(10), 692-702.
3. Poliseno, L., et al. (2010). A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature, 465(7301), 1033-1038.
4. Bird, A. (1986). CpG-rich islands and the function of DNA methylation. Nature, 321(6067), 209-213.

Intentional DNA alteration mechanisms challenge the neo-Darwinian view of random mutations and natural selection

Intentional DNA Alterations Point to Design and Creation

The complexity of cellular mechanisms and the intentional alterations of DNA within cells provide compelling evidence against the purely random processes proposed by neo-Darwinian evolution. Instead, these mechanisms suggest an intelligent design underlying biological systems. Cells possess the ability to make controlled changes to DNA sequences through various sophisticated mechanisms, challenging the notion that mutations are solely random events shaped by natural selection.

DNA Editing Mechanisms in Cells

Cells employ several mechanisms to intentionally alter DNA sequences. These mechanisms ensure that changes are purposeful and beneficial to the organism, rather than the result of random mutations. Three key mechanisms are base excision repair (BER), DNA methylation, and the activity of Apobec3G (A3G).

1. Base Excision Repair (BER) BER is a crucial cellular mechanism that repairs damaged DNA. When DNA bases undergo damage or mutation, BER can selectively remove the erroneous bases and replace them with the correct ones. This process involves a series of enzymes that identify the damaged base, excise it, and synthesize a new, correct base in its place. The precision of BER ensures the integrity of the genetic information, preventing harmful mutations from accumulating in the genome.

2. DNA Methylation DNA methylation is another sophisticated mechanism by which cells regulate gene expression and maintain genomic stability. This process involves the addition of methyl groups to cytosine residues, particularly in CpG islands. Methylation can silence genes by making DNA regions less accessible to transcription machinery. Interestingly, methylation patterns can be inherited, providing a means of epigenetic regulation across generations. Methylation can also lead to controlled DNA alterations, such as the deamination of methylated cytosine to thymine, which can be a programmed response to environmental stimuli.

3. Apobec3G (A3G) A3G is part of the Apobec family of enzymes that deaminate cytosine bases, converting them into uracil. This activity is particularly prominent in the defense against viral infections. By inducing hypermutations in viral DNA, A3G disrupts the replication of viruses such as HIV. This controlled alteration of DNA showcases the cell's ability to make targeted changes in response to specific threats. A3G's activity is regulated to prevent unwanted mutations in the host genome, highlighting an advanced level of cellular control.
   

   

4. ADAR Enzymes Adenosine Deaminases Acting on RNA (ADAR) enzymes convert adenosine to inosine in RNA molecules, which can lead to changes in the coding potential and splicing patterns of mRNA. This RNA editing process is crucial for normal brain function and immune response. By making these precise edits, ADAR enzymes provide another layer of control over genetic information and protein production.

Challenging Neo-Darwinian Theory

The ability of cells to make intentional and controlled alterations to DNA sequences challenges the neo-Darwinian view that mutations are purely random events. Neo-Darwinism posits that genetic variation arises from random mutations, which are then subject to natural selection. However, the existence of sophisticated DNA editing mechanisms suggests that cells can guide genetic changes in a purposeful manner.

1. Purposeful changes in DNA
   The concept of purposeful mutations aligns more closely with the idea of intelligent design than with random mutation and natural selection. The precision and regulation of DNA editing mechanisms indicate that cells were designed to make beneficial genetic changes deliberately. This challenges the notion that all genetic variation is random and instead supports the idea of a guided, intelligent process.

2. Adaptive Benefits
   The ability to make controlled DNA alterations provides significant adaptive benefits to organisms. For example, the immune response facilitated by A3G allows organisms to defend against viral infections effectively. Similarly, DNA methylation enables cells to regulate gene expression in response to environmental changes, ensuring that organisms can adapt to varying conditions. These adaptive responses are not random but are instead fine-tuned to enhance the survival and functionality of the organism.

3. Long-term Stability
   Epigenetic mechanisms like DNA methylation also offer long-term stability and inheritance of beneficial traits. This means that advantageous genetic changes can be passed down through generations without altering the underlying DNA sequence. Such stability is essential for maintaining complex biological functions and ensuring the continuity of life.

Implications for Design and Creation

The intentionality and complexity of DNA editing mechanisms strongly point to an intelligent design behind biological systems. These mechanisms are too precise and regulated to have arisen from random mutations alone. Instead, they suggest that life was designed with the ability to adapt and thrive in a dynamic environment.

1. Sophisticated Engineering The intricate processes involved in DNA editing resemble sophisticated engineering rather than random tinkering. The coordination between different cellular components to achieve precise genetic alterations indicates a level of planning and foresight that aligns with the concept of intelligent design.

2. Preservation of Functionality The ability to make controlled genetic changes ensures that essential functions are preserved, even in the face of environmental challenges. This preservation of functionality supports the idea that life was created with built-in mechanisms to maintain and enhance its complexity.

Conclusion

The existence of intentional DNA alteration mechanisms within cells provides strong evidence for intelligent design and creation. These mechanisms demonstrate that genetic changes can be purposeful, regulated, and beneficial, challenging the neo-Darwinian view of random mutations and natural selection. The sophisticated nature of DNA editing processes suggests that life was designed with the ability to adapt and thrive, pointing to an intelligent creator behind the complexity of biological systems.

References

1. News-Medical. (2023). Alternative splicing plays a role in compensating for loss of gene function. Retrieved from News-Medical
2. Nitschke, L., et al. (2023). Loss of MBNL1 leads to compensatory alternative splicing of MBNL2. Baylor College of Medicine.
3. DNA Methylation and Histone Modifications in Gene Regulation. (n.d.). Nature Education.
4. The Role of Non-coding RNAs in Alternative Splicing. (n.d.). Frontiers in Molecular Biosciences.
5. Harris, R. S., & Liddament, M. T. (2004). Retroviral restriction by APOBEC proteins. Nature Reviews Immunology, 4(12), 868-877.
6. Chen, S. H., & Gallo, R. C. (2003). DNA deamination and the APOBEC family of cytidine deaminases. Current Biology, 13(5), R174-R178.
7. Nishikura, K. (2016). A-to-I editing of coding and non-coding RNAs by ADARs. Nature Reviews Molecular Cell Biology, 17(2), 83-96.

DNA of Australian Aborigines is 99.9 identical to that of any other human being on Earth

The Genetic Unity of Humanity: Australian Aborigines and the 99.9% DNA Similarity

The field of genetics has provided profound insights into the unity of the human species. A striking discovery from the Human Genome Project, led by the National Human Genome Research Institute (NHGRI), is that all humans share 99.9% of their DNA. This remarkable genetic similarity underscores the shared heritage and close relationship among all human populations, including Australian Aborigines. This article will explore the genetic evidence supporting this claim, focusing on the mitochondrial DNA (mtDNA) haplogroups and the implications for understanding the history of Australian Aborigines from a biblical perspective.

The Genetic Homogeneity of Humans

The NHGRI's findings highlight that the vast majority of genetic variation lies within the 0.1% of the genome that differs among individuals. This small percentage accounts for all the diversity seen in human populations, including physical traits, susceptibility to diseases, and other characteristics. Australian Aborigines, despite their unique cultural and historical background, are no exception to this rule. Their DNA is 99.9% identical to that of any other human being on Earth.

Mitochondrial DNA and Haplogroups

Mitochondrial DNA (mtDNA), inherited maternally, provides valuable insights into ancient human migrations and population history. Human mtDNA can be categorized into several major haplogroups, which are further divided into sub-haplogroups. These haplogroups trace back to common maternal ancestors and can reveal significant information about human prehistory.

Australian Aborigines primarily belong to the mtDNA haplogroup N, one of the three major haplogroups along with M and R. From a biblical perspective, these haplogroups can be traced back to the descendants of Noah’s three sons: Japheth, Shem, and Ham. This framework suggests that after the Flood, the descendants of these three families repopulated the earth, giving rise to the various mtDNA haplogroups we see today.

Low mtDNA Variation Among Australian Aborigines

Genetic studies have shown that the mtDNA variation among Australian Aborigines is relatively low compared to other populations. This low variation suggests a long period of genetic stability and isolation. For example, a study by van Holst Pellekaan et al. (2006) found that the mtDNA diversity in Australian Aborigines is significantly lower than in other populations, supporting the idea of a long-standing, stable population with limited gene flow from outside groups.

Questioning the 50,000-Year Timeline

The prevailing scientific view posits that Australian Aborigines have been present on the continent for over 50,000 years. This timeline is based on archaeological discoveries and genetic estimates. However, the relatively low genetic variation observed in mtDNA among Australian Aborigines raises questions about the accuracy of these timelines. If Australian Aborigines had indeed been isolated for such an extended period, one might expect to see more genetic drift and variation within their mtDNA.

A Creationist Perspective

From a creationist perspective, the genetic evidence supports a more recent and rapid diversification of human populations. The observed genetic similarities among all human groups, including Australian Aborigines, align with the idea of a recent, common origin for all humans. The low mtDNA variation among Australian Aborigines can be interpreted as evidence of a shorter timescale for human history than the conventional model suggests.

Creationist researchers argue that the genetic data, rather than supporting a 50,000-year history for Australian Aborigines, indicates a more recent settlement and rapid adaptation to the Australian environment. This perspective challenges the deep-time evolutionary model and supports the biblical account of human history, which posits a young age for humanity. The biblical model suggests that after the Flood, Noah’s descendants quickly spread out and diversified, giving rise to the various genetic lineages observed today.

Conclusion

The genetic evidence, including the 99.9% DNA similarity among all humans and the specific mtDNA haplogroups of Australian Aborigines, underscores the unity of the human species. The low mtDNA variation among Australian Aborigines raises important questions about the conventional timelines of human history and supports a creationist interpretation of a more recent and rapid diversification of human populations. As genetic research continues to advance, it will provide further insights into the fascinating history and unity of humankind.

References

1. National Human Genome Research Institute (NHGRI). "The Human Genome Project."
2. van Holst Pellekaan, S. M., Ingman, M., Roberts-Thomson, J., & Harding, R. M. (2006). "Mitochondrial genomics identifies major haplogroups in Aboriginal Australians." Proceedings of the National Academy of Sciences.
3. Behar, D. M., et al. (2008). "The Dawn of Human Matrilineal Diversity." The American Journal of Human Genetics.
4. Answers in Genesis. "Uranium-Lead (U-Pb) Radioisotope Dating Method Problems."

The evidence increasingly supports the concept of an intelligently designed and created biological system

Stunning Intelligence: The Cell Reprograms Its Splicing Mechanism After Gene Loss

The intricate complexity of cellular mechanisms offers compelling evidence for intelligent design. A striking example is how cells adapt to gene loss through alternative splicing, a process that suggests an underlying intelligent programming. When a gene function is lost, the cell reprograms its splicing machinery to compensate, enhancing its efficiency. This remarkable ability points to a sophisticated system designed to preserve functionality and maintain life.

1. Intelligent Design in Alternative Splicing

The alternative splicing mechanism is a marvel of biological engineering, allowing a single gene to produce multiple protein variants. This process involves the selective inclusion or exclusion of RNA segments, producing diverse proteins from the same DNA template. The fact that cells can modify this already complex system in response to gene loss suggests an intelligent design rather than random mutation and selection. Such reprogramming requires a deep understanding of the organism's needs and a capacity to implement intricate changes rapidly and efficiently.

2. Human Understanding of Alternative Splicing

Despite significant advances in molecular biology, our understanding of alternative splicing remains limited. Scientists have only scratched the surface of this elaborate code. The complexity of alternative splicing involves numerous factors and regulatory elements that interact in highly specific ways. Our limited comprehension underscores the sophistication of the system, further pointing to an intelligent origin.

3. Factors Influencing Alternative Splicing

Several factors influence alternative splicing, each adding a layer of complexity to the process:

• DNA Methylation Profiles: Methyl groups added to DNA can affect splicing decisions by altering the accessibility of splicing machinery to specific regions.
• Histone Modifications: Chemical modifications to histone proteins, around which DNA is wrapped, can influence the splicing machinery's access to genetic information.
• RNA Molecules: Various non-coding RNAs can interact with the splicing machinery, guiding it to specific splice sites or altering its activity.

These factors collectively contribute to the regulation of alternative splicing, demonstrating an orchestrated system of checks and balances designed to maintain cellular functionality.

The Cell can produce thousands of different proteins by using the same pre-mRNA. There's no need to alter DNA. This is the most significant mechanism behind the protein diversity and adaptation of organisms.

4. DNA Rearrangement for Efficiency

When faced with gene loss, cells not only reprogram splicing mechanisms but also rearrange their DNA to maximize the use of remaining genetic information. This process involves selectively retaining or discarding DNA segments, and prioritizing sequences that enhance cellular efficiency and functionality. Such rearrangement requires a highly organized and intelligent system capable of evaluating and responding to genetic changes dynamically. This also emphasizes the role of DNA as a passive information storage for the cell.

Conclusion

The ability of cells to reprogram their alternative splicing mechanisms and rearrange DNA in response to gene loss highlights an intelligent design behind these processes. The sophisticated nature of these adaptations points to a system that is not the product of random mutations but of deliberate, intelligent programming. As we continue to unravel the complexities of alternative splicing and DNA rearrangement, the evidence increasingly supports the concept of an intelligently designed and created biological system.

References

• News-Medical. (2023). Alternative splicing plays a role in compensating for loss of gene function. Retrieved from News-Medical
• Nitschke, L., et al. (2023). Loss of MBNL1 leads to compensatory alternative splicing of MBNL2. Baylor College of Medicine.
• DNA Methylation and Histone Modifications in Gene Regulation. (n.d.). Nature Education.
• The Role of Non-coding RNAs in Alternative Splicing. (n.d.). Frontiers in Molecular Biosciences.

Radioisotope decay rates are not constant

Factors Influencing Radioisotope Decay Rates: Cavitation and Water

For many years, the assumption that radioactive decay rates are constant has been fundamental to dating rocks and understanding the age of the Earth. However, recent studies suggest that these rates may be more variable than previously thought.

Seasonal Fluctuations and Solar Neutrinos

Decades ago, researchers observed fluctuations in the decay rates of certain radioactive isotopes. These fluctuations were linked to the Earth's distance from the Sun, with decay rates accelerating when Earth is closest. This phenomenon is believed to be caused by solar neutrinos, which interact with atomic nuclei and influence decay rates​ (SpringerLink)​.

Cavitation and Thorium Decay

A groundbreaking study by Italian researchers demonstrated that cavitation can significantly accelerate the decay of thorium-228. Cavitation occurs when fast-flowing water creates vapor bubbles that collapse, producing powerful shock waves. These waves can impact atomic nuclei, increasing decay rates by a factor of 10,000 in just 90 minutes​ (SpringerLink)​ . This finding highlights the potential for environmental conditions to alter decay processes.

Helium in Zircon Crystals

Creation researchers have pointed to evidence of accelerated decay in the past, such as the high levels of helium found in zircon crystals associated with radioactive uranium. This suggests a historical event that dramatically increased decay rates.

Implications for Geological Dating

These discoveries challenge the stability of radioactive decay rates, suggesting that factors like cavitation and neutrinos can influence them. Consequently, the methods used to date geological formations and estimate the Earth's age may need to be reevaluated. This ongoing research underscores the complexity of nuclear decay and the potential for external influences to alter what was once considered a stable process.

Conclusion

The belief in the unwavering stability of radioactive decay rates is being reconsidered in light of new evidence. While the exact mechanisms behind these fluctuations are not fully understood, it is clear that decay rates can be affected by environmental factors such as cavitation and neutrinos. According to the latest research, it appears very clear that the global flood significantly affected the rates of radioisotope decay. This evolving understanding calls for a reexamination of the methods used to date the Earth and other geological features.

References

1. Jenkins, J. H., & Fischbach, E. (2009). Perturbation of nuclear decay rates during the solar flare of 2006 December 13. Astroparticle Physics, 31(6), 407-411.
2. Cardone, F., Mignani, R., & Petrucci, A. (2009). Piezonuclear decay of thorium. Physics Letters A, 373(22), 1956-1958.
3. Humphreys, D. R., Austin, S. A., Baumgardner, J. R., & Snelling, A. A. (2003). Helium diffusion rates support accelerated nuclear decay. In Proceedings of the Fifth International Conference on Creationism (Vol. 2, pp. 175-195).

DNA is passive information

Reasons Why DNA is Passive Information

Introduction

DNA (deoxyribonucleic acid) has long been hailed as the blueprint of life, encoding the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms. However, a closer examination reveals that DNA itself is passive information. This article explores several reasons why DNA alone does not dictate cellular identity and function, emphasizing the essential roles of epigenetic factors and cellular mechanisms.

1. Stem Cell DNA vs. Differentiated Cell DNA

Stem cells are undifferentiated cells capable of giving rise to various cell types. Despite possessing an intact and comprehensive genome, stem cells remain functionally inert until they receive epigenetic programming. This epigenetic programming involves modifications such as DNA methylation and histone modification, which do not alter the DNA sequence but affect gene expression.

For instance, DNA methylation can silence or activate specific genes, guiding the differentiation process. The unprogrammed state of stem cells underscores the passive nature of DNA; without epigenetic instructions, the genome remains an unused blueprint, waiting for cues to initiate cellular functions.

2. DNA Does Not Determine Cell Identity

If DNA were the sole determinant of cell identity and function, every cell with the same genetic material would exhibit identical characteristics. However, humans have approximately 300 distinct cell types, each performing unique roles. For example, a muscle cell and a hepatocyte both contain the same DNA but serve vastly different functions.

The differentiation into various cell types is guided by epigenetic mechanisms and factors. These factors include transcription factors, non-coding RNAs, and chromatin remodelers, which influence which parts of the DNA are transcribed into RNA and subsequently translated into proteins. Therefore, DNA provides the potential for various outcomes, but it is the epigenetic regulation that determines the specific expression patterns necessary for cell differentiation.

3. Cellular Mechanisms for DNA Reorganization

Cells possess intricate mechanisms to manage and reorganize their DNA, especially in response to genetic damage or loss of information. These mechanisms include homologous recombination, non-homologous end joining, and gene conversion processes. For instance, gene conversion during meiotic recombination (GbGC) can repair damaged DNA by copying sequences from a homologous chromosome.

Such repair and reorganization mechanisms highlight the cell’s ability to prioritize and utilize specific DNA sequences while discarding or rearranging others. Loss-of-function (LoF) variants are often tolerated if they do not impact essential genes or pathways, further emphasizing that DNA sequences are subject to cellular management and are not inherently active in determining cellular function without the cell's regulatory context.

Additional Reasons for DNA’s Passive Role

Beyond the primary points mentioned, several additional arguments support the notion of DNA as passive information:

Epigenetic Memory: Epigenetic marks can be inherited through cell divisions, maintaining gene expression patterns without altering the DNA sequence. This inheritance ensures that specialized cells retain their identity across generations, independent of the DNA sequence alone.

Environmental Influence: External factors such as diet, stress, and toxins can induce epigenetic changes that affect gene expression. These changes can be temporary or permanent, demonstrating that DNA is responsive to environmental cues rather than inherently directive.

Non-Coding DNA: A significant portion of the genome consists of non-coding DNA, which does not encode proteins but plays crucial regulatory roles. These non-coding regions include enhancers, silencers, and insulators that control the spatial and temporal expression of genes, further illustrating that DNA’s function is regulated rather than intrinsic.

Transcriptional Regulation: The process of transcription—the synthesis of RNA from DNA—is tightly controlled by a complex network of regulatory proteins and non-coding RNAs. These factors determine which genes are transcribed and indicate that DNA itself is not the active player in directing transcription.

Conclusion

While DNA is indispensable as the genetic material, it functions primarily as passive information within the cell. The epigenetic programming, regulatory mechanisms, and environmental interactions collectively govern the expression and functionality of the genome. Understanding DNA as passive information highlights the complexity of gene regulation and the multifaceted nature of cellular identity and differentiation. It helps us understand why DNA doesn't dictate organismal traits or characteristics. This understanding does not diminish the significance of DNA as a sophisticatedly organized, efficient source of biological information storage.

References

1. Bird, A. (2007). Perceptions of epigenetics. Nature, 447(7143), 396-398.
2. Jaenisch, R., & Bird, A. (2003). Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature Genetics, 33, 245-254.
3. Riggs, A. D., Martienssen, R. A., & Russo, V. E. A. (1996). Epigenetic mechanisms of gene regulation. Cold Spring Harbor Laboratory Press.
4. Kouzarides, T. (2007). Chromatin modifications and their function. Cell, 128(4), 693-705.
5. Allis, C. D., Jenuwein, T., & Reinberg, D. (2007). Epigenetics. Cold Spring Harbor Laboratory Press.
6. Tollervey J R, Lunyak V V. Epigenetics: judge, jury and executioner of stem cell fate. Epigenetics Official Journal of the DNA Methylation Society. 2012, 7(8):823.
7. Cheng Y, Xie N, Jin P, et al. DNA methylation and hydroxymethylation in stem cells. Cell Biochemistry & Function. 2015, 33(4):161-173.
8. Lunyak V V, Rosenfeld M G. Epigenetic regulation of stem cell fate. Human Molecular Genetics. 2008, 17(R1):R28.
9. Luigi A, Santiago D, Luciano D C. ZRF1: a novel epigenetic regulator of stem cell identity and cancer. Cell Cycle, 2015, 14(4):510-515.
10. Srinageshwar B, Maiti P, Dunbar G L, et al. Role of Epigenetics in Stem Cell Proliferation and Differentiation: Implications for Treating Neurodegenerative Diseases. International Journal of Molecular Sciences. 2016, 17(2):199.

The complex relationship between epigenetic modifications and genomic stability

Epigenetic regulation results in genetic entropy

The conversion of methylated cytosine to thymine is associated with chromosome breaks and fusions. This process is part of a broader context involving DNA methylation, mutations, and genome instability. Here’s an explanation based on current scientific understanding:

Methylated Cytosine and its Conversion to Thymine

1. Methylation Process:

   • Cytosine can be methylated to form 5-methylcytosine (5mC), a common epigenetic modification that plays a role in gene expression regulation.
   • This methylation typically occurs in CpG dinucleotides, regions where a cytosine nucleotide is followed by a guanine nucleotide.

2. Deamination of 5mC:

   • 5mC is prone to spontaneous deamination, converting it to thymine (T). This mutation is one of the most common point mutations in the human genome.
   • If not corrected by DNA repair mechanisms, this leads to a G
     to A transition mutation.

Chromosomal Breaks and Fusions

1. Genome Instability:

   • Regions of the genome that are heavily methylated are often more prone to mutations. These mutations can lead to genome instability, increasing the likelihood of chromosomal breaks.
   • When repair mechanisms fail, these breaks can result in chromosomal rearrangements, including fusions.

2. Role of DNA Repair Mechanisms:

   • DNA repair mechanisms, such as base excision repair (BER), are responsible for correcting deaminated 5mC. However, errors in these repair processes can lead to double-strand breaks (DSBs).
   • DSBs are particularly harmful and can lead to chromosomal translocations, deletions, and fusions if repaired incorrectly.

3. Epigenetic Changes and Cancer:

   • Abnormal DNA methylation patterns and the resulting mutational changes are commonly observed in cancer cells. These changes contribute to the chromosomal abnormalities characteristic of many cancers.
   • Studies have shown that regions with high 5mC content are hotspots for mutations and chromosomal rearrangements in various types of cancers.

Conclusion

Chromosome fusions result from the loss of information, which is strongly connected to the conversion of methylated cytosine to thymine, a process typically occurring in epigenetic regulation. It is pseudoscientific to claim that genetic errors led to the evolution of apes into humans.

The conversion of methylated cytosine to thymine is a mutation that contributes to genome instability and can lead to chromosomal breaks and fusions. This universal mutational process, coupled with defective DNA repair mechanisms, significantly impacts chromosomal integrity and is associated with various diseases, including cancer. Understanding these mechanisms further elucidates the complex relationship between epigenetic modifications and genomic stability.

Evolution has no mechanism. Genetic entropy is a biological fact.

References:

Several studies support the connection between methylated cytosine, its conversion to thymine, and chromosomal instability:

• Duncan, B. K., & Miller, J. H. (1980). Methylation of cytosine to 5-methylcytosine enhances the mutation rate of cytosine to thymine, particularly in CpG islands, leading to potential mutagenic hotspots in the genome.

• Bestor, T. H. (1990). DNA methylation and its role in genome defense and genome stability, including the consequences of 5mC deamination and the role of methylation in chromosomal integrity.

• Feinberg, A. P., & Vogelstein, B. (1983). Hypomethylation of DNA as a chromosomal mutator in human cancer. They discuss how changes in methylation patterns contribute to chromosomal instability and cancer.

• Matsuda, A., et al. (2015). The role of DNA methylation in chromosomal instability and how this leads to cancer progression through mechanisms like chromosomal breaks and translocations.

It is difficult to find evolutionary intermediates because they simply do not exist

Rapid mtDNA Mutation Rate Points to a Young Creation

Recent genetic research has revealed compelling evidence that challenges the traditional evolutionary paradigm and supports a young creation model. The study of mitochondrial DNA (mtDNA) sequences has shown that the genetic diversity within and among various species is surprisingly low, suggesting a much more recent origin for life than previously thought.

Clear Distinctions Between Organism Groups

Biological classification systems, such as the taxonomic system, group organisms into clear categories like genus, family, and order. These categories correspond to what the Bible refers to as "kinds." For example, dogs, cats, camels, hawks, turtles, and dolphins each form distinct kinds. Importantly, organisms within a kind exhibit significant variation but do not cross the boundaries into other kinds. This is evident in the rapid and efficient epigenetic variation observed within kinds, contrasted by an insurmountable gap between different kinds. There are no intermediate forms bridging these gaps, which poses a significant challenge to the theory of evolution.

Darwin's Dilemma of Missing Intermediate Forms

Charles Darwin himself acknowledged the problem of missing intermediate forms in the fossil record, which he considered one of the most serious objections to his theory. He expected the gradual transition of species over long periods, yet the fossil record does not support this expectation. Instead, it shows distinct groups with no clear transitional forms, aligning more closely with the creation model that suggests organisms were created as distinct kinds.

Uniform mtDNA Variation

If evolution were true, we would expect to see a continuum of mtDNA variation reflecting millions of years of gradual change. However, a comprehensive study by researchers D.S. Thaler and M.Y. Stoeckle published in 2018, which analyzed over five million mtDNA sequences from more than 100,000 animal species, found otherwise. They discovered that the genetic diversity within species, including humans, is remarkably consistent, with mtDNA variation at most 0.1%. This uniformity suggests that all species have a similar origin time.

Implications of mtDNA Mutation Rate

The study's findings indicate that about 90% of all species appeared around the same time, approximately 100,000 to 200,000 years ago, according to the researchers' evolutionary assumptions. However, these assumptions are based on an mtDNA mutation clock calibrated within the evolutionary framework. Empirical studies have shown that the actual mutation rate of mtDNA is much faster than this calibrated rate—about 20 times faster. If Thaler and Stoeckle had used an empirically based mutation rate, their results would suggest that species emerged only 5,000 to 10,000 years ago.

Supporting a Young Creation Model

The low genetic diversity and the lack of intermediate forms support the idea that species were created as distinct kinds relatively recently. This conclusion is consistent with the biblical creation account, which posits that life on Earth is thousands, not millions, of years old. As Dr. Thaler noted, the genetic world is not a blurry place; it is difficult to find evolutionary intermediates because they simply do not exist.

The findings of Thaler and Stoeckle provide strong evidence against the neo-Darwinian model of evolution, which assumes gradual changes over millions of years. Instead, the data align with a creationist perspective, suggesting a rapid origin of species within a much shorter timeframe. This perspective is further supported by the consistent mtDNA variation observed across diverse species, indicating a recent and simultaneous origin for much of life on Earth.

Conclusion

In conclusion, the rapid mtDNA mutation rate and the resulting low genetic diversity across species provide compelling evidence for a young creation. The lack of intermediate forms further challenges the evolutionary model and supports the idea that life was created as distinct kinds. These findings underscore the need to reconsider the traditional evolutionary timelines and acknowledge the possibility of a much younger origin for life on Earth.

References:

M.Y. Stoeckle and D. S. Thaler. 2018. “Why Should Mitochondria Define Species?,” Human Evolution 33, no. 1–2: 1–30. DOI: 10.14673/HE2018121037.

All Necessary DNA Sequences Present in Each Cell for Skin Color Pigments

Every Human Skin Cell Contains All the Necessary DNA Sequences Responsible for Known Skin Color Pigments

Introduction

Human skin color is a so-called polygenic trait influenced by environmental factors. It is determined by the type and amount of pigment produced by melanocytes in the skin. These pigments, primarily eumelanin, and pheomelanin, are synthesized through complex biochemical pathways governed by various genes. Remarkably, every human skin cell contains all the necessary DNA sequences to produce these pigments, but their expression is regulated by intricate epigenetic mechanisms.

If race or skin color could be analyzed from a DNA sample, companies that analyze DNA samples would easily be able to tell the sender what their skin color is. However, companies in the field are unable to do this. DNA tests can predict skin color with only about 60% accuracy at best.

Key Genes Involved

Several genes are known to play pivotal roles in skin pigmentation:

• MC1R (Melanocortin 1 Receptor): This gene regulates the balance between eumelanin (dark pigment) and pheomelanin (light pigment) production.
• TYR (Tyrosinase): This enzyme is crucial for the initial steps in melanin biosynthesis.
• OCA2 (Oculocutaneous Albinism II): Influences melanin production and distribution in melanocytes.
• SLC45A2 (Solute Carrier Family 45 Member 2): Affects the transportation of substances necessary for melanin synthesis.
• HERC2: Regulates the expression of OCA2 and thus impacts melanin production indirectly.    

Epigenetic Regulation

DNA Methylation and Histone Modification

Epigenetic regulation, including DNA methylation and histone modifications, plays a crucial role in the differential expression of pigmentation genes. DNA methylation typically suppresses gene expression by adding methyl groups to cytosine bases, particularly in CpG islands. Histone modifications, such as acetylation and methylation, alter the chromatin structure, making it more or less accessible for transcription.

Alternative Splicing

Alternative splicing is another critical mechanism contributing to the diversity of protein products from a single gene. It allows for the generation of multiple mRNA variants from one gene, leading to different protein isoforms. For instance, Ensembl lists 64 splicing variants for the genes involved in skin pigmentation (HERC2, OCA2, MC1R, ASIP, SLC45A2, IRF4, TYR, TYRP1, GRM5, HYAL1 sekä HYAL3), underscoring the complexity of pigment production and regulation.

All Necessary DNA Sequences Present in Each Cell

Every human skin cell possesses the complete set of DNA sequences required for the production of known skin color pigments. However, whether these genes are active or not depends on epigenetic regulation:

• Epigenetic Modifications: These changes determine the accessibility of genes to the transcriptional machinery. For example, highly methylated regions are typically less active.
• Histone Marks: Specific histone modifications can either promote or inhibit the transcription of pigment-related genes.

Conclusion

The ability of human skin cells to produce different skin pigments is embedded in their complex splicing and histone code, and each cell has all the necessary DNA sequences. The regulation of these genes through epigenetic mechanisms such as DNA methylation, histone modifications, and alternative splicing determines the actual pigment production. Understanding these processes sheds light on the complexity of human skin pigmentation and highlights the intricate balance between epigenetic regulatory mechanisms.

DNA doesn't determine human skin color. There is only one human race.

The Connection between Epigenetic regulation and Deletional Bias

The connection between Epigenetic regulation, C→T mutational bias, and Deletional bias

There is a connection between strong deletional bias and the C→T mutational bias, particularly related to the tendency of methylated cytosines to turn into thymines. Let's break down how these two processes are connected:

1. C→T Mutational Bias:

• Methylation of Cytosine: In many organisms, cytosine residues in DNA can be methylated to form 5-methylcytosine, a common epigenetic modification.
• Deamination of 5-Methylcytosine: 5-Methylcytosine is prone to spontaneous deamination, which converts it to thymine. This results in a C→T transition mutation.
• Repair Mechanisms: When this C→T mutation occurs, it can sometimes escape the DNA repair mechanisms, leading to a permanent mutation.

2. Deletional Bias:

• Genome Stability: The genome tends to undergo deletions more frequently than insertions due to several reasons, such as errors during replication, DNA repair processes, and the activity of mobile genetic elements.
• Deletion Hotspots: Certain regions of the genome, particularly those with repetitive sequences or high methylation, are more prone to deletions.

Connection Between the Two:

• CpG Sites as Mutational Hotspots: CpG sites, where cytosine is followed by guanine, are hotspots for mutations because cytosine in these dinucleotides is often methylated. When 5-methylcytosine deaminates to thymine, it creates a mismatch (G-T) during DNA replication. If not repaired correctly, this leads to a permanent C→T mutation.

• Impact on Genome Structure: The regions with high CpG content, which are more prone to C→T mutations due to methylation, are also areas where deletions can occur more frequently. This is because the altered DNA sequences can lead to instability and make these regions more susceptible to deletions.

• Loss of Regulatory Areas: Over time, the combined effect of C→T mutations and deletions can lead to a reduction in CpG sites, as the genome becomes more stable. This can create a bias where deletion events are more common in regions with high CpG content.

Empirical Evidence:

1. Studies on Human Genomes:

   • Human genome studies have shown that CpG dinucleotides are underrepresented compared to what would be expected based on base composition alone. This is largely due to the high mutation rate at these sites (C→T transitions), coupled with deletions that further reduce CpG density.
   • Reference: Fryxell KJ, Moon WJ. (2005). "CpG mutation rates in the human genome are highly dependent on local GC content." BMC Genomics.
   

2. Change in Genomics:

   • Comparative genomics studies indicate that regions with high methylation and high CpG content tend to undergo more deletions. These deletions, combined with C→T mutations, contribute significantly to the change of genome structure.
   • Reference: Huff JT, Zilberman D. (2014). "Dmi1-Independent DNA Methylation Dynamics and Gene Regulation in Archaea." Nature.

Conclusion:

The connection between strong deletional bias and C→T mutational bias is primarily driven by the mutational instability of methylated cytosines at CpG sites. The high rate of C→T transitions due to the deamination of 5-methylcytosine, combined with the propensity for deletions in these regions, leads to a significant reduction in CpG sites and contributes to genomic instability leading to genetic entropy. This interplay highlights the complex relationship between epigenetic modifications, mutational processes, and genome dynamics.

Evolution never happened.

Ten famous examples of evolution debunked

Re-evaluating Evolution: The Role of Epigenetic Regulation in Ten Famous Examples

Introduction

The concept of evolution, as traditionally understood, relies heavily on the accumulation of genetic mutations followed by natural selection. However, recent advances in epigenetics suggest that many well-known examples of evolution may actually be explained by epigenetic regulation rather than changes in the DNA sequence. Epigenetics involves the modification of gene expression without altering the underlying DNA sequence, often through mechanisms such as DNA methylation, histone modification, and non-coding RNA. Here, we expose ten famous evolutionary claims through the lens of epigenetic regulation.

1. Darwin’s Finches

Darwin’s finches, often cited as a classic example of natural selection, show variations in beak size and shape that correlate with dietary habits. Recent studies suggest that these differences are driven by epigenetic changes in response to dietary factors, rather than random genetic mutations. No evolution.

2. Peppered Moths

The case of the peppered moth is a classic example used to illustrate natural selection. The frequency of dark-colored (melanic) moths increased in industrial areas of Britain during the 19th century due to the selective advantage they gained by blending into soot-covered trees, thus avoiding predation. Recent studies suggest that this change in pigmentation may not be genetic but influenced by epigenetic mechanisms such as alternative splicing and RNA editing.

In peppered moths, the gene responsible for pigmentation changes is the cortex gene. This gene has been shown to undergo alternative splicing, which can result in different pigmentation patterns. This splicing variation can be influenced by environmental factors, such as pollution levels, which affect how the gene is expressed and, consequently, the moth's coloration.

Furthermore, RNA editing, particularly adenosine-to-inosine (A-to-I) editing, plays a role in modifying mRNA transcripts that code for pigmentation proteins. This type of RNA editing can alter the function of proteins involved in pigment synthesis, leading to variations in coloration without altering the underlying DNA sequence. No evolution.

3. Antibiotic Resistance in Bacteria

While antibiotic resistance is often considered a clear example of genetic evolution, epigenetic mechanisms play a more significant role. Bacteria can rapidly adapt to antibiotics through epigenetic modifications (m6a methylation) that regulate gene expression involved in resistance. Another mechanism is DNA arrangement after a loss of information. No evolution.

4. Cichlid Fish in African Lakes

Cichlid fish display a remarkable diversity of forms and behaviors. Research indicates that epigenetic regulation, particularly DNA methylation, is responsible for the rapid phenotypic changes observed in these fish, allowing them to adapt quickly to different ecological niches. No evolution.

5. The Italian Wall Lizard

The introduction of the Italian wall lizard to a new environment led to rapid morphological changes, such as the development of cecal valves. These changes have been linked to epigenetic modifications in response to dietary shifts, rather than genetic mutations. No evolution.

6. Stickleback Fish

Stickleback fish exhibit different morphologies in freshwater versus marine environments. Epigenetic changes, particularly in gene expression related to ion transport and osmoregulation, have been implicated in these adaptations. No evolution.

7. Domestication of Animals

The domestication of animals, including dogs and livestock, shows dramatic changes in behavior and physiology. These changes are increasingly understood to be driven by epigenetic modifications induced by human interaction and selective breeding practices. No evolution.

8. Plant Adaptation to Altitude

Plants such as Arabidopsis have shown rapid adaptation to high-altitude environments. Epigenetic changes, particularly in DNA methylation patterns, allow these plants to quickly adjust their physiology to cope with lower oxygen levels and increased UV radiation. No evolution.

9. Coral Bleaching

Coral bleaching, a response to environmental stressors like increased water temperature, involves epigenetic changes that affect the expression of heat-shock proteins. These modifications help corals survive in changing conditions but also illustrate the role of epigenetics in rapid environmental response. No evolution.

10. Lactose Tolerance in Humans

The ability to digest lactose in adulthood, a trait that evolved in some human populations, is not solely due to genetic mutations in the lactase gene. Epigenetic regulation of lactase gene expression also plays a crucial role, influenced by dietary habits and cultural practices. No evolution.

Conclusion

These examples demonstrate that many classic cases of evolution have nothing to do with assumed evolution. Epigenetic mechanisms allow for rapid and reversible changes in gene expression in response to environmental stimuli, offering a plausible explanation for the observed phenotypic diversity without relying on genetic mutations or imaginary selection. The theory of evolution is the most serious heresy of our time.

References

1. Skinner, M. K. (2014). Environmental epigenetics and a unified theory of the molecular aspects of evolution: A neo-Lamarckian concept that facilitates neo-Darwinian evolution. Genome Biology and Evolution, 6(6), 1231-1237.
2. van der Oost, R., Komen, H., & Doornbos, G. (2018). Epigenetic variation in the peppered moth. Nature Ecology & Evolution, 2(10), 1520-1526.
3. Wittebole, X., De Roock, S., & Opal, S. M. (2014). A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence, 5(1), 226-235.
4. Lamboj, A. (2011). The cichlid fishes of western Africa. Tetra Press.
5. Herrel, A., et al. (2008). Rapid large-scale evolutionary divergence in morphology and performance associated with exploitation of a different dietary resource. Proceedings of the National Academy of Sciences, 105(12), 4792-4795.
6. Jones, F. C., et al. (2012). The genomic basis of adaptive evolution in threespine sticklebacks. Nature, 484(7392), 55-61.
7. Axelsson, E., et al. (2013). The genomic signature of dog domestication reveals adaptation to a starch-rich diet. Nature, 495(7441), 360-364.
8. Richardson, D. M., et al. (2000). Plant invasions--the role of mutualisms. Biological Reviews, 75(1), 65-93.
9. Palumbi, S. R. (2005). The evolutionary ecology of marine animals: Coral bleaching and the adaptation potential of reef corals. Marine Ecology Progress Series, 301, 273-277.
10. Enattah, N. S., et al. (2008). Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture. The American Journal of Human Genetics, 82(1), 57-72.
11. Badisco, L., Huybrechts, J., & Simonet, G. (2013). Alternative splicing in insects: Role in the regulation of sipe and wing development. Insect Biochemistry and Molecular Biology.

Epigenetic Regulation doesn't lead to evolution

Epigenetic Mechanisms and the Impossibility of Evolutionary Change

Introduction

Epigenetic mechanisms play a crucial role in regulating gene expression without altering the underlying DNA sequence. These processes involve chemical modifications such as DNA methylation, histone modification, and RNA-associated silencing. Key players in these mechanisms include epigenetic readers, writers, and erasers, which interpret, add, and remove epigenetic marks, respectively. While these mechanisms are vital for cellular function and development, they are insufficient to drive evolutionary change. This article explores why epigenetic mechanisms do not lead to evolution, focusing on the role of methylated cytosine and its propensity to mutate into thymine, resulting in genetic entropy.

Epigenetic Readers, Writers, and Erasers

Epigenetic regulation involves a sophisticated interplay of proteins known as readers, writers, and erasers. Writers, such as DNA methyltransferases, add methyl groups to DNA, typically at cytosine residues in CpG islands. Readers, including methyl-CpG-binding domain proteins, recognize these modifications and recruit other proteins to influence chromatin structure and gene expression. Erasers, such as ten-eleven translocation (TET) enzymes, remove methyl groups, allowing for dynamic regulation of the epigenome.

Despite their crucial roles, these proteins operate within a framework of existing genetic information. They do not introduce new genetic sequences or significantly alter the genetic code. Instead, they modify the expression of genes already present in the genome, acting as a regulatory layer rather than a source of novel genetic material.

The Vulnerability of Methylated Cytosine

A critical issue with relying on epigenetic mechanisms for evolutionary change is the instability of methylated cytosine. Methylated cytosine (5mC) is prone to spontaneous deamination, converting it into thymine. This C-to-T transition is one of the most common mutations in the human genome and leads to a permanent alteration if not repaired before DNA replication.

The persistence of such mutations contributes to genetic entropy, a gradual decline in genetic information over generations. This process undermines the idea that epigenetic modifications can drive evolutionary progress. Instead, it highlights a mechanism of genetic decay, where beneficial changes are rare and harmful mutations accumulate.

Consequences of Increased AT Content

The conversion of 5mC to T increases the AT content of the genome, leading to several issues. High AT content is associated with genomic instability, making chromosomes more prone to breakage and improper recombination during cell division. This instability can result in large-scale genomic rearrangements, deletions, and duplications, often with deleterious effects on the organism.

To counterbalance the increase in AT content, cells employ mechanisms like GC-biased gene conversion (gBGC) during meiosis. However, this process is not perfect and often leads to further loss of genetic information. As the genome undergoes these compensatory adjustments, the overall genetic integrity diminishes, contributing to genetic entropy.

Conclusion

Epigenetic mechanisms, while essential for gene regulation, do not provide a basis for evolutionary change. The inherent instability of methylated cytosine and the resultant increase in AT content lead to genetic entropy rather than innovation. The regulatory nature of epigenetic modifications and their susceptibility to causing harmful mutations further emphasize that they cannot drive the evolutionary process. Instead, these mechanisms highlight the limitations and vulnerabilities of the genome, underscoring the need for a re-evaluation of their role in evolutionary theory.

References

1. Jones, P. A. (2012). Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nature Reviews Genetics, 13(7), 484-492.
2. Schübeler, D. (2015). Function and information content of DNA methylation. Nature, 517(7534), 321-326.
3. Riggs, A. D., & Xiong, Z. (2004). Methylation and epigenetic fidelity. Proceedings of the National Academy of Sciences, 101(1), 4-5.
4. Yi, C., & He, C. (2013). DNA repair by reversal of DNA damage. Cold Spring Harbor Perspectives in Biology, 5(1), a012575.
5. Lynch, M. (2010). Evolution of the mutation rate. Trends in Genetics, 26(8), 345-352.

Causes and Mechanisms Leading to Genetic Entropy

One of the primary mechanisms contributing to genetic entropy is the universal tendency of methylated cytosine to mutate into thymine. This CpG->TpG transition is not effectively repaired by the cell if replication occurs before the repair. As a result, there is a gradual increase in the AT content of the genome.

The increase in AT content can lead to several problems:

1. Genetic Instability: Higher AT content can cause chromosomal breakages and structural abnormalities.
2. Loss of Regulatory Elements: CpG sites are often found in promoter regions, and their mutation can disrupt gene regulation.
3. Increased Mutation Rates: High AT regions are more prone to further mutations.

To counterbalance the rising AT content, cells employ various mechanisms to maintain GC-AT content equilibrium. One significant method is GC-biased gene conversion (gBGC) during meiotic recombination, where passive DNA is rearranged to increase GC content. However, this process often leads to a loss of genetic information.

In conclusion, while repair mechanisms work to mitigate these changes, they are not entirely efficient. The accumulation of mutations, especially the irreversible CpG->TpG changes, leads to a progressive loss of biological information over time, supporting the concept of genetic entropy.

Chromosomal Structural Fragility and AT Content

Multiple studies have shown that chromosomal structural fragility may be associated with specific DNA sequences, particularly AT-rich regions:

AT-Rich Sequences and Fragility: AT-rich sequences can cause the formation of DNA secondary structures, which may lead to replication disturbances and consequently chromosomal breaks. For example, AT-rich minisatellites and microsatellites are known to have fragile sites.

Fragile Sites: Research has shown that AT-rich regions containing repetitive sequences can act as "fragile sites," which are prone to breaks during replication stress or other cellular stresses.

Chromosome Fusions Chromosome fusions, where two chromosomes join to form a single chromosome, can result from various mechanisms, including repair errors of breaks:

Telomere Shortening and Fusions: Telomere shortening can lead to unprotected chromosome ends, resulting in breaks and fusions. AT-rich sequences in telomere regions may be involved in this process.

Non-Homologous End Joining (NHEJ): Chromosome fusions can occur when broken chromosome ends join together through the NHEJ mechanism. This process is more error-prone, especially in AT-rich sequences, which can complicate precise joining.

Instability of AT-Rich Regions A common observation is that AT-rich regions are generally more unstable than GC-rich regions:

Genomic Instability: AT-rich regions may be more unstable and prone to mutations, leading to structural changes in chromosomes, such as fusions and breaks.

Summary and conclusions:

• There is a universal tendency of methylated cytosine to mutate into thymine. A methylated cytosine is ~20,000 more prone to turn to thymine than non-methylated cytosine.
• Adaptation needs often result in changing methylation patterns (epigenetic regulation).
• This CpG->TpG transition is not effectively repaired by the cell if replication occurs before the repair.
• There is a gradual increase in the AT content of the genome.
• The only way the cell can balance the GC-AT ratio is gBGC gene conversion. DNA is rearranged.
• DNA is passive information.
• In this procedure information is typically lost.
• High AT content is associated with chromosomal structural fragility, chromosome breakages, and fusions.
• Genetic entropy is an inevitable universal biological phenomenon.
• Evolution never happened.

Example Studies:

Ruiz-Herrera et al. (2006): The study demonstrated that AT-rich regions are more prone to chromosomal structural rearrangements in some animal species.

Zlotorynski et al. (2003): The study focused on fragile sites and showed that these regions are often AT-rich and associated with chromosomal instability.