Neurons migrating through dense tissue in the developing brain (green) frequently undergo DNA damage (magenta).
Like my last post, this post illustrates how the human body, far from being the perfect design of the omnipotent, omniscient designer creationists would have us believe in, is the result of a utilitarian evolutionary process. Layers of complexity arise, not from divine brilliance, but from evolved solutions to problems created by suboptimal earlier solutions to other problems — which were themselves the result of imperfect evolution.
In the previous post we saw how DNA replication is sufficiently imperfect that it requires mechanisms to repair the resulting DNA damage. However, these repair processes are themselves potentially dangerous and need control systems to maintain a careful balance between too little and too much repair. When this control process fails, it can lead to cancers that mimic those caused by the BRCA1 and BRCA2 genes, which are associated with increased risk of breast and ovarian cancer.
In this post we see how newborn neurons in the developing brain need to squeeze through tight spaces in dense tissue, past other cells and between fibres, in order to reach their final positions and form neural circuits in the cerebral and cerebellar cortices. This process is such a physical struggle that the DNA in these neurons can suffer double-strand breaks and must be repaired quickly to ensure normal brain development. This is the finding of a research team from Kyoto University, the University of Tokyo, Osaka University, the National University of Singapore and the Tokyo Metropolitan Institute of Medical Science, led by Professor Mineko Kengaku who have just published their findings in Nature.
Mostly, this repair is quick and successful. However, the research team also found striking similarities between the development of mice in which the repair process failed and human genome-instability syndromes that affect the cerebellum.
Another important point is that this repair process appears to be much more successful in damaged neuronal DNA than in similar damage that can occur when some cancer cells migrate through narrow channels. The difference seems to lie in where the DNA breaks occur. In neurons, they tend to occur in regions of the genome that are not actively being transcribed, whereas in cancer cells the damage can involve essential genes. That suggests there is some biological bias in where these breaks occur in neurons, rather than the process being simply random mechanical shattering.
This raises the obvious question for creationists: why create a process that breaks DNA in developing brain cells, only to require another process to repair it, with the inherent risk that the repair process might be incomplete or imperfect? It also raises the possibility that the resulting small differences in the genomes of individual neurons could contribute to neuronal individuality and perhaps to some neurodevelopmental or neurodegenerative diseases.
The emerging picture, from this and from the rogue repair-control process that can mimic cancers caused by the BRCA genes, is not of a human body designed by an omniscient engineer. It is more like a William Heath Robinson contraption: improvised, overcomplicated, dependent on compensatory mechanisms, and always vulnerable to the failure of the very systems needed to keep it working.
Why biological systems are so complex. Living systems are full of processes that only work because additional layers of control, repair or damage limitation have evolved to compensate for earlier imperfections. These are not the hallmarks of clean, intelligent design, but of historical tinkering: systems patched, monitored and rescued by other systems.The paper on neuronal DNA damage and repair was accompanied by a news item from Kyoto University:
- DNA replication and mismatch repair: Copying DNA is impressively accurate, but only because DNA polymerases proofread their own work and separate mismatch-repair systems correct errors that escape the first check. The copying system needs an error-correction system bolted onto it.
- DNA damage and cell-cycle checkpoints: Cells frequently suffer DNA damage from replication errors, radiation, chemicals and normal metabolism. Rather than preventing the damage in the first place, cells use checkpoints to pause division while repair is attempted. If the damage is too severe, the cell may be driven into apoptosis — programmed cell death.
- Protein folding and the unfolded protein response: Proteins do not always fold correctly. Cells therefore need molecular chaperones, quality-control systems, ER-associated degradation and the unfolded protein response to detect, refold or destroy defective proteins before they cause damage.
- Immune self-tolerance: The immune system is powerful enough to attack the body it is supposed to defend. It therefore needs layers of self-tolerance, including deletion or inactivation of self-reactive immune cells and regulatory mechanisms to suppress misdirected responses. When these controls fail, autoimmune disease can result.
- Blood clotting and anticoagulant control: Blood must clot quickly after injury, but the same clotting system can kill if it activates in the wrong place. The clotting cascade therefore needs counter-regulatory systems, including anticoagulant pathways and fibrinolysis, to prevent useful clotting becoming thrombosis.
- Oxygen metabolism and antioxidant defences: Aerobic respiration is efficient, but it produces reactive oxygen species that can damage DNA, proteins and membranes. Cells therefore need antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase to mop up the toxic by-products of their own metabolism.
- Cell division and spindle checkpoints: Chromosomes must be accurately separated during cell division, but the process is error-prone. The spindle checkpoint delays chromosome separation until the machinery appears to be properly attached. When it fails, cells can inherit the wrong number of chromosomes.
- Inflammation and anti-inflammatory controls: Inflammation is useful for fighting infection and repairing tissue, but it is also destructive. The body therefore needs anti-inflammatory signals and resolution pathways to switch it off. Failure to control it can lead to chronic inflammatory disease.
In each case, the pattern is the same: an imperfect process is made survivable by adding another process to monitor, repair, restrain or destroy the products of its failure. That is just what we would expect from evolution working with inherited constraints, but not what we would expect from an omniscient designer, unconstrained by history and lack of available resources, starting with a clean sheet and working to a plan.
Complexity is the hallmark of bad design; intelligent design is minimally complex.
More examples of how the human body refutes intelligent design can be found in The Body of Evidence: How The Human Body Refutes Intelligent Design.
DNA in neurons is damaged and repaired during brain cortex formation
Researchers find that neurons routinely sustain DNA breaks during cortex formation, but a rapid repair system corrects the damage before harm occurs.
Newborn nerve cells must squeeze through crowded, narrow spaces—through dense tissue, past other cells, between fibres—to reach the areas where they form neural circuits in the brain cortex.
In a new study published in Nature, researchers at Kyoto University's Institute for Integrated Cell-Material Sciences (WPI-iCeMS) and their collaborators report that this journey causes widespread DNA damage in neurons, resulting in double-strand breaks where both strands of the double helix are completely severed. While this is the most severe type of DNA damage—capable of causing mutations and cell death—the team surprisingly found that it is a normal, routine feature of brain cortex formation, and a healthy brain quickly repairs it before harm occurs.
"The developing brain appears to have evolved to tolerate and repair the neuronal damage efficiently, but understanding the limits of that tolerance—and what happens when repair is incomplete—brings us closer to understanding a range of neurological conditions.
Professor Mineko Kengaku, senior author.
Institute for Integrated Cell-Material Science (WPI-iCeMS)
Kyoto University
Kyoto, Japan.
The team mimicked the journey by guiding neurons through microchannels designed to replicate the narrow spaces in developing brain tissue. Fluorescent markers revealed DNA double-strand breaks forming as the cells passed through the channels, then disappearing after they had reached the other side. Most were repaired within 24 hours, with no lasting effects on function.
The researchers traced the DNA breaks to Topoisomerase IIβ, an enzyme that normally makes controlled cuts in DNA to release the torsional strain of everyday cellular activity. It’s similar to snipping a twisted cable to untangle it and then splicing it back together. Under mechanical stress, the enzyme becomes stuck mid-process, leaving broken ends of DNA. A repair pathway—known as non-homologous end joining—stitches these broken ends back together.
This differs sharply from what happens in some cancer cells migrating through the same microchannels, where DNA damage occurs more randomly, impairing cellular function or even killing the cells. In neurons, this damage occurs mainly in non-critical regions of the genome rather than in active genes, so overall function is preserved.
To test what happens if this repair fails, the team engineered mice in which new neurons in the cerebellum lacked Ligase 4, a key repair enzyme. The animals developed normally, but they gradually showed mild, progressive balance difficulties from early adulthood—symptoms reminiscent of human genome instability syndromes that affect the cerebellum.
The findings raise new questions about whether these early breaks contribute to neuronal individuality and to neurodevelopmental and neurodegenerative diseases.
It shifts how we think about the neuronal genome. All neurons originate from the same DNA, but DNA damage and repair can introduce small genetic differences between individual neurons through a small mechanical journey. Some of that history may be written into the genome itself.
Professor Mineko Kengaku.
The work was a collaboration between Kyoto University and groups at the University of Tokyo, the University of Osaka, the National University of Singapore, and the Tokyo Metropolitan Institute of Medical Science.
Publication:
Here again we see the same familiar pattern: not a clean, elegant, intelligently designed system, but an evolved workaround for a problem created by another evolved workaround. Developing neurons must migrate through crowded embryonic tissue to reach their proper places in the brain, but in doing so they risk breaking their own DNA. That damage then has to be repaired, and the repair process itself has to be sufficiently accurate and rapid to prevent developmental failure.
This is not what we would expect from a perfect designer starting with a blank sheet and unlimited power. Such a designer could have arranged for neurons to form where they were needed, or for their DNA not to be vulnerable to mechanical stress during migration. Instead, what we find is the familiar evolutionary signature of constraint, compromise and contingency: a system that works well enough most of the time, but only because additional layers of rescue machinery have evolved to keep its failures within survivable limits.
And, as always, when these compensatory systems fail, creationism has no explanatory framework beyond hand-waving appeals to mystery, sin, “The Fall”, or the inscrutable will of the creator. Science, by contrast, identifies the mechanism, tests it, compares it with related systems, and shows why it matters for development and disease. The result is another small but telling example of a body assembled by evolution, not designed by omniscience.
The human brain may be capable of astonishing things, but its development depends on risky, makeshift processes that need constant monitoring and repair. That is exactly the sort of thing evolution produces: functional, often ingenious, but never perfect, never planned, and never free from the legacy of its own history.
Advertisement
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
All titles available in paperback, hardcover, ebook for Kindle and audio format.
Prices correct at time of publication. for current prices.
No comments :
Post a Comment
Obscene, threatening or obnoxious messages, preaching, abuse and spam will be removed, as will anything by known Internet trolls and stalkers, by known sock-puppet accounts and anything not connected with the post,
A claim made without evidence can be dismissed without evidence. Remember: your opinion is not an established fact unless corroborated.