Developmental defects of double, triple and quadruple mutants in RNA-dependent RNA polymerase (rdr1, rdr2, rdr6) and DNA methylation (ddm1) in floral organ identity, leaf shape and fertility (silique length).
The secret to being a good designer or planner is to always have a Plan B. I say that as a former emergency operations centre manager where the future is unpredictable, so I needed to keep as many options open as possible because, as I used to joke, my Plan B was to tear up Plan A and start again.
Now, you can play the percentages game, for example, I could be fairly sure town centres would be fairly busy around 11 pm, especially on a Friday and Saturday night, when in the UK the pubs close, or as we call it, 'chucking out time', and a lot of inebriated people would be out on the streets, fighting over available taxis, over girl/boyfriends or who had got served at the bar out of turn (queue-jumping is a big no-no in the UK).
I also knew from 17 years operational experience that most of the calls would require little more than smoothing ruffled feathers, running checks to exclude underlying medical problems and sending them on their way, so turnover time would be relatively short, and I would get a crew back fairly quickly.
Another peak would be around 1 am when the nightclubs closed, but with a few exceptions such as those the rest of the week would resemble a system in chaos where medical emergencies, traffic accidents and every other imaginable emergency occurred more or less randomly, with statistical patterns only being noticeable over time with a sufficiently large database.
Later on, I became the data analyst who looked for those patterns and used them to devise deployment plans to minimise average emergency response times, but that's another story.
Juggling acts were the daily routine for an emergency operations centre like mine, as we tried to maintain as much emergency cover as possible while getting help to people who needed it as quickly as possible. And you never knew you had made the right decision until it turned out not to have been the wrong one.
Our major handicap was of course being unable to accurately forecast the future, not just weeks or days ahead but hours and minutes. What we singularly lacked was omniscience for which educated guesses were a poor substitute.
So, to a creationist it might come as something of a shock to learn that their putative designer behaves like a designer/planner who can't foretell the future because, if nothing else, it is allegedly omniscient, and its designs are perfect. As such it shouldn't need a Plan B because Plan A will be perfectly designed for the precise future needs of the species. There should never be an occasion where it needs to tear up Plan A and starts again; it shouldn’t need to consult a large database to look for patterns then work out the probability of that pattern repeating itself and planning its responses accordingly, never knowing if it was the right plan until it turned out not to be.
And yet a team of researchers from Cold Spring Harbor Laboratory, New York, USA has found that the plant, Arabidopsis has a Plan B for when Plan A fails. Plan A is all about making the ramshackle, Heath Robinson process for ensuring mistakes in DNA replication get attended to. In a design which seems to be a characteristic of creationism putative intelligent [sic] designer, a shoddy process needs another layer of complexity to try to make it works, but even that fix breaks and the result of growth defects, sterility and, in many cases in animals, cancers or developmental disorders.
What information do you have on the roles of DDM1 and RNAi in cell division? DDM1 (Decrease in DNA Methylation 1) and RNAi (RNA interference) play significant roles in gene regulation, but they function in different contexts, including chromatin remodeling, epigenetics, and gene silencing. Here’s an overview of their roles, particularly in the context of cell division:What the team found is that Arabidopsis thaliana has the 'normal' molecule that most other species have - known as DDM1 - which ensures the centromere on every chromosome divides correctly. If this fails in humans, for example, it results in a sever genetic condition known as ICF syndrome. And yet, Arabidopsis thaliana managed perfectly well without it.
- DDM1 (Decrease in DNA Methylation 1):
- Function: DDM1 is a chromatin remodeler that regulates DNA methylation, particularly in *Arabidopsis thaliana* and other plants. DDM1 belongs to the SWI/SNF family of chromatin remodeling proteins and is involved in maintaining methylation patterns at transposable elements (TEs) and repetitive DNA sequences.
- Mechanism: By modifying the chromatin structure, DDM1 allows DNA methylation machinery (e.g., methyltransferases) to access DNA more effectively, particularly in densely packed heterochromatin regions. Without DDM1, methylation is significantly reduced, which can lead to genomic instability due to the activation of transposons.
- Role in Cell Division: DDM1 plays an indirect role in cell division by maintaining genomic stability. Proper methylation and suppression of transposons are critical for the accurate replication of the genome during the cell cycle, especially in regions of heterochromatin.
- RNAi (RNA Interference):
- Function: RNAi is a gene-silencing mechanism that uses small RNAs (siRNAs or miRNAs) to target and degrade specific mRNA molecules, preventing the production of the corresponding protein. RNAi is widely used in various organisms as a defense mechanism against viruses, transposons, and other genetic elements.
- Mechanism: Small RNA molecules guide the RNA-induced silencing complex (RISC) to complementary mRNA sequences, leading to the degradation or suppression of the target mRNA, effectively silencing gene expression. This can also include silencing of repetitive elements or viral sequences.
- Role in Cell Division: RNAi contributes to genome stability by silencing transposons, particularly in germline cells and during early development. It ensures that the genomic integrity is preserved during the cell division process by preventing harmful genetic elements from being expressed. RNAi can also be involved in the regulation of genes important for the progression of the cell cycle, ensuring proper cell cycle checkpoints and division.
In Combination:
Both DDM1 and RNAi are critical for maintaining genomic integrity:
By working through different pathways—epigenetic regulation by DDM1 and post-transcriptional regulation by RNAi—both processes help ensure that genomic stability is preserved during cell division, protecting against mutations or transposon-induced damage.
- DDM1 maintains methylation and silencing of transposable elements at the chromatin level.
- RNAi silences transposons and foreign DNA at the RNA level.
This is because it has Plan B in the form of a small RNA molecules which function as an RNA inhibitor (RNAi). The team have just published their findings, open access, in Nature Plants and announced it in a Cold Spring Harbor Laboratory press release:
Plants have a backup plan
Tending a garden is hard work. Imagine it from the plants’ perspective. Each relies on fine-tuned genetic processes to pass down accurate copies of chromosomes to future generations. These processes sometimes involve billions of moving parts. Even the tiniest disruption can have a cascading effect. So, for plants like Arabidopsis thaliana, it’s good to have a backup plan.
Chromosomes have to be accurately partitioned every time a cell divides. For that to happen, each chromosome has a centromere. In plants, centromeres control chromosome partitioning with the help of a molecule called DDM1.
Professor Robert A. Martienssen, senior author
Howard Hughes Medical Institute
Cold Spring Harbor Laboratory, New York, NY, USA.
Martienssen discovered DDM1 in 1993 with a team that included Tetsuji Kakutani, then a postdoc with CSHL Fellow Eric Richards. Kakutani and Martienssen recently reunited to investigate a question 30 years in the making. When humans lose their version of DDM1, centromeres can’t divide evenly. This causes a severe genetic condition called ICF syndrome. But if the molecule is so important, why isn’t Arabidopsis affected when DDM1 is lost? Martienssen explains:We wondered why it would be so different. About 10 years later, we found that in yeast, centromere function is controlled by small RNAs. That process is called RNAi. Plants actually have both DDM1 and RNAi. So, we thought, ‘Let’s isolate these two in Arabidopsis to see what happens.’ We did that, and sure enough, the plants looked really horrible.
Professor Robert A. Martienssen.
When the team looked closer, they found that a single transposon inside chromosome 5 was responsible for the defects. Transposons move around the genome, switching genes on and off. In Arabidopsis, they trigger DDM1 or RNAi to help centromeres divide. But when DDM1 and RNAi are missing, the process is disrupted.
We found very few copies of this transposon anywhere else in the genome. But the centromere of chromosome 5 was infested with these things. We thought, ‘Wow, OK, this really might be it.’ Then we started working on how to restore healthy function.
Professor Robert A. Martienssen.
Left: Arabidopsis thaliana with healthy centromere division.Right: A mutant version of Arabidopsis with uneven centromere division.Those small RNAs make up for the loss of DDM1. They recognized every copy of the transposon in the centromere and, amazingly, restored centromere function. So now the plants were fertile again. They make seeds. They look much better.
Professor Robert A. Martienssen.
Of course, it’s not all about plants. In humans, uneven centromere division has been linked to conditions like ICF and early cancer progression. Martienssen hopes his team’s work may one day point to better treatments for these and other diseases.
Publication:Shimada, A., et al.,
Retrotransposon addiction promotes centromere function via epigenetically activated small RNAs Nature Plants, September 2, 2024. DOI: 10.1038/s41477-024-01773-1
AbstractCreationists who might be tempted to marvel at the amazing complexity of these processes and wave it around as evidence of the super-intelligence of the putative creator, should consider that this is only needed because the cell replication process includes an error-prone method for replicating the entire genome in every cell when only a small subset of it will ever be needed by the daughter cells. And the additional layer of complexity which is only needed to repair those errors is also prone to errors.
Retrotransposons have invaded eukaryotic centromeres in cycles of repeat expansion and purging, but the function of centromeric retrotransposons has remained unclear. In Arabidopsis, centromeric ATHILA retrotransposons give rise to epigenetically activated short interfering RNAs in mutants in DECREASE IN DNA METHYLATION1 (DDM1). Here we show that mutants that lose both DDM1 and RNA-dependent RNA polymerase have pleiotropic developmental defects and mis-segregate chromosome 5 during mitosis. Fertility and segregation defects are epigenetically inherited with centromere 5, and can be rescued by directing artificial small RNAs to ATHILA5 retrotransposons that interrupt tandem satellite repeats. Epigenetically activated short interfering RNAs promote pericentromeric condensation, chromosome cohesion and chromosome segregation in mitosis. We propose that insertion of ATHILA silences centromeric transcription, while simultaneously making centromere function dependent on retrotransposon small RNAs in the absence of DDM1. Parallels are made with the fission yeast Schizosaccharomyces pombe, where chromosome cohesion depends on RNA interference, and with humans, where chromosome segregation depends on both RNA interference and HELLSDDM1.
Main
Eukaryotic centromeres are usually composed of repetitive sequences with a unique chromatin composition that includes the centromeric histone H3 variant CENH3 (ref. 1). CENH3 assembles the kinetochore, a large protein complex that attaches the chromosome to the spindle1. The positioning of CENH3 is thought to be epigenetically defined by surrounding pericentromeric heterochromatin—chromosomal material that remains condensed in interphase2,3. Pericentromeric heterochromatin is also responsible for sister chromatid cohesion at mitosis, which ensures segregation of sister chromatids to each daughter cell during anaphase1. In many eukaryotes, these repetitive centromere sequences are composed of rapidly evolving tandem satellite repeats1,2. In plants, animals and fungi, satellite repeats are interspersed with specific classes of retrotransposons but the function, if any, of these retrotransposons has remained obscure1.
DNA methylation and RNA interference (RNAi) are important epigenetic pathways for both transcriptional and post-transcriptional gene silencing. In the model plant Arabidopsis thaliana, DNA methylation is required to silence transposons, and can be triggered by RNAi through a pathway called RNA-dependent DNA methylation (RdDM). RdDM relies on 24-nt siRNAs produced by RNA POLYMERASE IV, RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) and DICER-LIKE 3 (DCL3)4,5. These 24-nt small RNAs bind to ARGONAUTE 4 (AGO4) and related proteins, which are thought to recruit DNA methyltransferases to RNA POLYMERASE V, along with other chromatin-modifying enzymes4,5. In organisms without DNA methylation, such as Drosophila melanogaster, Caenorhabditis elegans and the fission yeast S. pombe, RNAi guides histone modifications, notably dimethylation of histone H3 lysine-9 (refs. 6,7,8), which plays a major role in centromere cohesion. For this reason, S. pombe RNAi mutants have strong defects in chromosome segregation9,10. However, in Arabidopsis, such mitotic defects are very mild, or not apparent, when components of the canonical RdDM pathway are mutated, despite the complete loss of the 24-nt small RNA11.
DNA methylation can be maintained in the absence of RdDM by the DDM1 SWI2/SNF2 chromatin remodeler, but mutants retain fertility and normal chromosome segregation despite substantial demethylation of centromeric satellite repeats12. Although RdDM-mediated DNA methylation is required for transcriptional gene silencing, Arabidopsis possesses another RNAi pathway for post-transcriptional gene silencing, which generates 21-nt or 22-nt siRNAs via RDR6-DCL2/DCL4-AGO1/AGO7 and silences euchromatic genes, transgenes and viral RNAs13. We previously identified a class of 21-nt epigenetically activated short interfering RNAs (easiRNAs) derived from transposable elements in ddm1 mutants14, which have elevated transcription of transposons15. Similar small RNAs are found in ddm1-like double mutants in maize, although mutant embryos fail to germinate in this species16. We rationalized that small RNAs might compensate for the loss of DNA methylation in ddm1 mutants, and set out to determine the developmental and chromosomal consequences of removing RNAi in the absence of DNA methylation.
Shimada, A., Cahn, J., Ernst, E. et al.
Retrotransposon addiction promotes centromere function via epigenetically activated small RNAs.
Nat. Plants 10, 1304–1316 (2024). https://doi.org/10.1038/s41477-024-01773-1
Copyright: © 2024 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
In the case in point these are then 'rectified' by yet another layer of complexity in the form of a back-up process, and because the 'designer' could not foresee when the errors would occur or design a process that wasn't prone to error. Needing several layers of complexity to compensate for error-prone designs at all levels, all because the initial cell-replication process was unnecessarily complex in the first place, is not the act of an intelligent designer.
It is however, the act of a mindless, utilitarian process in which whatever is better than before tends to be retained, warts and all. And so, we have the unnecessarily complex system that charcterises evolved organisms and which give the lie to claims of intelligent design by a perfect, omniscient designer, which would be minimally complex and free from errors that need to be rectified.
Nor would there be a need for Plan B for when Plan A fails due to unforeseen circumstances.
The Unintelligent Designer: Refuting The Intelligent Design Hoax
ID is not a problem for science; rather science is a problem for ID. This book shows why. It exposes the fallacy of Intelligent Design by showing that, when examined in detail, biological systems are anything but intelligently designed. They show no signs of a plan and are quite ludicrously complex for whatever can be described as a purpose. The Intelligent Design movement relies on almost total ignorance of biological science and seemingly limitless credulity in its target marks. Its only real appeal appears to be to those who find science too difficult or too much trouble to learn yet want their opinions to be regarded as at least as important as those of scientists and experts in their fields.
Available in Hardcover, Paperback or ebook for Kindle
The Malevolent Designer: Why Nature's God is Not Good
This book presents the reader with multiple examples of why, even if we accept Creationism's putative intelligent designer, any such entity can only be regarded as malevolent, designing ever-more ingenious ways to make life difficult for living things, including humans, for no other reason than the sheer pleasure of doing so. This putative creator has also given other creatures much better things like immune systems, eyesight and ability to regenerate limbs that it could have given to all its creation, including humans, but chose not to. This book will leave creationists with the dilemma of explaining why evolution by natural selection is the only plausible explanation for so many nasty little parasites that doesn't leave their creator looking like an ingenious, sadistic, misanthropic, malevolence finding ever more ways to increase pain and suffering in the world, and not the omnibenevolent, maximally good god that Creationists of all Abrahamic religions believe created everything. As with a previous book by this author, "The Unintelligent Designer: Refuting the Intelligent Design Hoax", this book comprehensively refutes any notion of intelligent design by anything resembling a loving, intelligent and maximally good god. Such evil could not exist in a universe created by such a god. Evil exists, therefore a maximally good, all-knowing, all-loving god does not.
Illustrated by Catherine Webber-Hounslow.
Available in Hardcover, Paperback or ebook for Kindle
Illustrated by Catherine Webber-Hounslow.
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