Wednesday 31 May 2023
Yet even more primeval tech vs. Darwin
Cellulose Doesn’t Just Happen
“Wood” you believe that the most abundant biopolymer on Earth requires a host of machines, genes, proteins, and accessories? Cellulose is only made by life. It doesn’t emerge fully formed from volcanoes or abiotic chemistry. To paraphrase Aristotle, if the art of cellulose manufacture were within atoms, we would have cellulose by the nature of atomic physics.
(Aristotle was reasoning that something else than raw nature was needed for shipbuilding: namely, art, which presupposes intelligence and purpose. “If the art of ship-building were in the wood,” he quipped, “we would have ships by nature.”)
Cellulose is most commonly understood as the chief component of the cell walls of plants. It is also manufactured, however, by some microbes like bacteria and algae, fungi and slime molds, and urochordates (tunicates). Each organism makes cellulose according to its needs; bacteria, for example, do not need the extra machinery to make long fibrils that plants need.
In a Primer in Current Biology, Lise C. Noack and Staffan Persson (hence N&P) described “Cellulose synthesis across kingdoms.” As evolutionists, they attribute the art of cellulose manufacture to evolution: “Other proteins evolved before the emergence of the hexameric rosette structure,” they say in one place.
Cellulose synthesis is present in all kingdoms of life and is characterized by an evolutionarily conserved BcsA/CesA synthase.
Evolutionary conservation is not evolutionary at all, it goes without saying; it means stasis. But having asserted that cellulose synthesis emerged and evolved (or not), the hard work of explaining its origin is put off the table. Most of the article deals with how cellulose is made.
Building Blocks on Other Building Blocks
The basic building block of cellulose is the sugar glucose, a six-carbon ring structure with the formula C6H12O6. Notably, glucose is not found in abiotic nature either. It is only a product of living cells. Although NASA has claimed some sugars have been detected in meteorites, I could find no reference to glucose being formed outside of living organisms.
One NIH paper from 2022 starts, “Gluconeogenesis is the pathway by which glucose is formed from non-hexose precursors such as glycerol, lactate, pyruvate, and glucogenic amino acids.” Already we see, even before cellulose synthesis begins, its monomer glucose must be “formed” by a “pathway” in a living cell. Those words suggest an organized process that assembles prior building blocks. N&P bypass that point, assuming the prior existence of glucose in the cell:
Cellulose consists of glucose molecules connected through beta-1,4-acetal linkages, which are generated by cellulose synthases and result in the formation of unbranched glucan chains.
Bacterial Cellulose Synthase
Surprisingly, N&P’s Figure 1 shows more components in the bacterial synthase machinery than in the plant machinery.
The protein complex that synthesizes cellulose was first discovered in bacteria, where it consists of a core complex composed of two subunits — BcsA and BcsB — and many accessory proteins, the presence of which varies depending on bacterial species (Figure 1A). BcsA is strictly speaking the cellulose synthase because it carries the cytosolic glycosyltransferase domain, as well as a transmembrane domain that allows for cellulose translocation and a regulatory carboxy-terminal PilZ domain that senses cyclic di-GMP (Figure 2A).
We’re just getting started, and already a supply of previously manufactured glucose molecules are needed in the right place at the right time, where the machinery is embedded in the bacterial inner membrane. Then we need the protein complex BcsA with its two subunits, and “many accessory proteins.” But getting the parts list right is only a beginning. The parts have to work together in functional harmony.
The machinery needs to link the glucose molecules together and then translocate them to the outer membrane. This is done by two more protein complexes, BcsB and BcsC. They won’t work correctly without another component: a regulator that senses cyclic di-GMP, abbreviated c-di-GMP. N&P gloss over that detail, so now we must look that up. Nature Reviews says,
c-di-GMP controls cellular processes at the transcriptional, translational and post-translational level, and through an increasing number of c-di-GMP-binding proteins and riboswitches.
We have lost count of the number of components to make cellulose and get it moved to where it is needed, and this is in a bacterium! Consider just one of the other machines:
BcsB is the cocatalytic subunit or co-polymerase because its presence is required for cellulose polymerization. It contains a periplasmic carbohydrate-binding domain that might guide the glycan chain towards the outer membrane secretory components.
The term cocatalytic implies cooperation between machines. This component, furthermore, must guide the chain to where it is needed. Another machine, BcsZ, regulates the arrangement of the polymers.
Plant Cellulose Synthase
The cellulose machinery in plants has fewer components but more functional requirements. It doesn’t need the two translocators BcsB and BcsC, because the polymers go directly from the inner membrane to the cell wall. Instead of the polymerase BcsA, plants and some algae combine the glucose molecules into polymers with a machine called CesA.
The authors speculate about a possible ancestral relationship between CesA and the bacterial BcsA synthase, but admit that “the phylogenetic relevance of terminal complex organization is still somewhat unclear.” Whatever; CesA in plants is arranged in geometrically-perfect “rosettes” of six sets of 3 CesA domains held together with three other proteins, PCR, CSR, and NTD. The rosette structure gives plant cellulose its cable-like formation, woven like strands of a rope. These cables confer the strength needed to support tall trees.
At the risk of getting too deep in the weeds, this quote gives a taste of the complexity of making cellulose. Conserved, remember, means not evolved.
At the level of the amino-acid sequence, the glycosyltransferase domain has four conserved regions: the first three each contain a D residue, whereas the fourth contains a Q(Q/R)xRW motif. The resulting D–D–D–Q(Q/R)xRW motif is conserved in all BcsA and CesA proteins and is essential for glycosyltransferase function. This highlights a remarkable conservation from sequence to tertiary protein folding, indicative of a conserved enzymatic mechanism. Apart from the D–D–D–Q(Q/R)xRW motif, plant and some algae CesA proteins have three additional domains that are likely involved in protein oligomerization: an amino-terminal RING-like zinc-finger domain (NTD), a plant-conserved region (PCR) and a class-specific region (CSR) (Figure 2B). Although the role of the NTD in CesA oligomerization is still unclear, the PCR and CSR domains are thought to be responsible for the rosette architecture of the cellulose synthase complex in plants (Figure 2C).
N&P discuss some of the similarities and differences in these machines within different species. Some parts are interchangeable, they note. Those details do not affect the overall impression that many parts are needed to make cellulose. Bacterial cellulose polymers can be less organized, because they contribute to biofilm formation. In plants, though, the polymers are shaped into microfibrils, sheets, or ribbons.
There is a strong correlation between terminal complex organization and microfibril dimensions. Rosette CesA complexes from plants and algae form small-diameter microfibrils ranging from 2 to 3.5 nm. However, single or multiple row arrangements of terminal complexes can give rise to much wider and thicker microfibrils, up to 25 nm in diameter, or flat ribbons of cellulose up to 100 nm in width. Depending on the structure, cellulose microfibrils engage with a variety of other polysaccharides and glycoproteins to form complex networks.
Just when our heads are spinning trying to remember all the parts, N&P discuss “Additional subunits of the cellulose synthase complexes.” I count at least 17 more proteins “involved in different regulatory aspects of cellulose synthesis.”
Let’s recap the importance of cellulose with this quote from a chemistry lesson from Imperial College London:
Cellulose is another glucose polymer (molecular weight 150,000-1 million) found in the cell walls of plants. Over 50% of the total organic matter in the world is cellulose. For example, wood is about 50% cellulose, and cotton is almost 100% cellulose. It is a strong, rigid linear molecule, and these features allow it to be used as the main structural support for plants. The glucose units are again held together by linkages, but this time every second glucose unit is flipped over. These links are called b,1:4 linkages, and human bodies do not possess the enzymes necessary to break this bond. Therefore any cellulose we eat passes through the digestive tract undigested, and acts as roughage. Grass feeding animals, such as cows, however, can digest cellulose, since they have extra stomachs to contain the grass for long periods while it is broken down by special bacteria.
Because of the enormous number of parts, machines and regulators involved in cellulose manufacture, we have wood, lumber, and shipbuilding. The art of shipbuilding may not be in the wood, but what would Aristotle have thought about the art of cellulose manufacture therein?
It's design all the way down.
Model Cell Visualized as a Compact Factory
In Episode 6 of Michael Behe’s video series Secrets of the Cell, the animator portrayed little human factory workers, robots, and machines at work inside a magnetotactic bacterial cell. The cartoon characters are seen managing energy production, loading docks with miniature forklifts, coding software, packaging the iron-containing magnetosomes for delivery on conveyor belts, and doing all kinds of things that we can relate to at a human level. Real cells, though they operate with many of the same functional requirements, are squishy. They don’t look like the animation. How can we visualize the innards of a cell in a way that relates the actual appearance to the factory-like operations that go on?
Capturing all the interior parts of a cell in their complex relationships took a lot of work, but some researchers have set a new high bar for biophysical imaging. The Allen Institute in Seattle issued news on April 1 that describes their work visualizing the “shape space” of a typical cell. Senior Scientist Matheus Viana explains the thinking:
“We know that in biology, shape and function are interrelated, and understanding cell shape is important to understand how the cells function,” Viana said. “We’ve come up with a framework that allows us to measure a cell’s shape, and the moment you do that you can find cells that are similar shapes, and for those cells you can then look inside and see how everything is arranged.”
Shape Space Is Function Space
The first task of their project was to get the exterior shape nailed down. Identifying the shape of healthy genetically engineered stem cells was not easy, because they are squishy. No two are identical, even when grown under the same conditions. Stem cells in the middle of the epithelial tissue sample have different shapes than those on the edges. Complicating the task further is the fact that not all similar cells are performing the same functions at the same time. Some may be undergoing mitosis when observed; this profoundly affects the cell’s shape.
The researchers found that most of their 215,081 cells were bean-shaped or pear-shaped to various degrees. By measuring the “bean-ness” and “pear-ness” of thousands of cells according to 8 shape criteria, they arrived at an average shape. This allowed them to study the locations of 25 organelles and other interior parts which they followed using fluorescent tags.
The result is the rotating model cell shown in the press release. It bears a distant resemblance to Behe’s compartmentalized factory. Notice their own words revealing similarities:
When they looked at the position of the 25 highlighted structures, comparing those structures in groups of cells with similar shapes, they found that all the cells set up shop in remarkably similar ways. Despite the massive variations in cell shape, their internal organization was strikingly consistent.
If you’re looking at how thousands of white-collar workers arrange their furniture in a high-rise office building, it’s as if every worker put their desk smack in the middle of their office and their filing cabinet precisely in the far-left corner, no matter the size or shape of the office.
One might apply this description to the Behe cell factory image. The control center, import center and delivery center tend to follow a predictable internal organization.
Visualizing Functional Changes During Mitosis
The Allen Institute team’s first dataset comprised a “large baseline population of cells in interphase.” Then, they studied the shapes of cells at the outer edges of epithelial tissues. Both of those datasets involved static images. Things became really interesting when they added the 4th dimension: time. Their crowning achievement was a 3D model incorporating observations of dividing cells — mapping all 25 organelles and structures — during five stages of mitosis. The result is a colorful, interactive “Interactive Mitotic Stem Cell” that biologists will find profoundly interesting to explore at IMSC.AllenCell.org.
I strongly recommend readers spend a little time at the site. It reminds me of a project described in Illustra’s film Metamorphosis, where biologist Richard Stringer took a time series of MRI images of a butterfly chrysalis, sliced them into hundreds of frames, and built a 3D model of what goes on during the transformation from chrysalis to butterfly. Illustra color-coded the structures so that viewers could watch from any angle as the wings take shape, the digestive system gets dramatically rearranged, and all the new organs for the adult are constructed.
Similarly, in the Allen Cell visualization tool, viewers can watch what happens to each organelle during mitosis. This is a much richer experience than students get in high school biology, where the focus is usually on the chromosomes. Now, one can see what happens to the mitochondria, the Golgi apparatus, the nucleolus, the nuclear envelope, lysosomes, gap junctions, actin filaments and everything else during five mitotic stages. Viewers can spin and magnify the cell, switch the 25 organelles on and off, play a rotation animation, and watch the parts in different degrees of detail.
The team noticed that some organelles stay relatively stable during mitosis, migrating to the apical nodes, while others like the nuclear envelope and Golgi undergo dramatic changes, essentially disintegrating and reorganizing into new structures like marching band players in a “scatter” formation. Biology teachers will love this visualization tool. For ID advocates, it opens new opportunities for design-based hypotheses: for instance, what orchestrates each organelle’s particular sequence of changes from one cell into two cells, and what controls their spatial relationships to other organelles?
The Allen team sees their “shape space” tool as a complement to protein-based studies.
Other systematic image-based approaches have catalogued the location of human proteins in several cell types and used the locations of proteins and structures within cells to identify differences in intracellular spatial patterns among cells in distinct states. Our work complements these approaches with its focus on analyses of 3D cell organization at the intermediate level of cellular structures (rather than individual proteins), and on the generation of quantitative measurements of distinct aspects of organization, which enables statistical comparisons and provides a more nuanced, systematic definition of cellular organization and reorganization. Together, these studies bring a crucial missing dimension — that is, the spatiotemporal component — to the single-cell revolution. The full image dataset and analysis algorithms introduced here, as well as all the reagents, methods, and tools needed to generate them, are shared in an easily accessible way (https://www.allencell.org/). These data are available to all for further biological analyses and as a benchmark for the development of tools and approaches moving towards a holistic understanding of cell behaviour.
Having a model of a normal healthy cell digitized in a computer, medical professionals will be able to identify abnormal states earlier. Watch the Darwin-free video “How do you measure a human cell?” to witness the excitement they experienced when their model cell was all put together after seven years of work. And this is just the beginning. The new model was all for one cell type, but a human body has many different cell types acting in multiple situations, subject to different pathologies.
“This study brings together everything we’ve been doing at the Allen Institute for Cell Science since the institute was launched,” said Ru Gunawardane, Ph.D., Executive Director of the Allen Institute for Cell Science. “We built all of this from scratch, including the metrics to measure and compare different aspects of how cells are organized. What I’m truly excited about is how we and others in the community can now build on this and ask questions about cell biology that we could never ask before.”
Viana’s very large team published their results open access in Nature on January 4. The only things that “evolved” in the paper were the scientists’ own intelligently designed techniques for imaging and setting up experiments. Everything else was in “machine language”—
Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challengeowing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behavioursthat they determine. Here we reduced this complexity by focusing on cellular organization — a key readout and driver of cell behaviour — at the level of major cellular structures that represent distinct organelles and functional machines, and generated the WTC-11 hiPSC Single-Cell Image Dataset v1, which contains more than 200,000 live cells in 3D, spanning 25 key cellular structures.
The Allen team’s pioneering effort to digitize a 3D normal stem cell undergoing mitosis can now be expanded by other teams who want to investigate other cell types — neurons, muscle cells, erythrocytes, bone cells — in any other organism from microbe to mammal. I’m reminded of pictures of various embryonic mammals in the womb: a giraffe taking shape, an elephant, a mouse. Once the basic sequence of gestation was visualized for the human, it became fascinating to look for similarities and differences in other mammals. Similarly, the Allen project visualizing a “model stem cell” begins what will surely lead to additional models for other cell types.
If, as ID advocates know from experience, specified complexity in biology grows as a function of detail, the future looks bright for design apologetics. Leeuwenhoek would have been amazed.
Anecdote
There’s news about magnetotactic bacteria that Dr. Behe discussed in his video. The Helmholtz Association for German Research Centres reports (via Phys.org) that these microbes can remove heavy metals, including uranium, from wastewater. “Due to their structure, they are positively predestined for such a task,” the article says, noting that they can be easily separated from water using magnets. Notable quotes:
Because they exhibit a feature that differentiates them from other bacteria, magnetotactic bacteria form nanoscopic magnetic crystals within the cell. They are arranged like a row of beads and so perfectly formed that humans would currently be unable to reproduce them synthetically. Each individual magnetic crystal is embedded in a protective membrane.
Together, the crystals and membrane form the so-called magnetosome which the bacteria use to align themselves with the Earth’s magnetic field and orientate themselves in their habitat. It also makes them suitable for simple separation processes.
Magnetotactic bacteria can be found in almost any aqueous environment from fresh water to saltwater, including environments with very few nutrients. Microbiologist Dr. Christopher Lefèvre has even discovered them in the hot springs of Nevada.
In search of Adam and Eve?
Protein Evolution, the Waiting-Time Problem, and the Intriguing Possibility of Two First Parents
On a new episode of ID the Future, host Eric Anderson gets an update on the recent work of Dr. Ann Gauger, Senior Fellow at Discovery Institute’s Center for Science and Culture. Dr. Gauger explains her continuing research into the limits of protein evolution, efforts that are challenging prevailing assumptions about the role of proteins and mutations in a Darwinian account of life. She also discusses her work on the related waiting times problem, demonstrating the difficulty for Darwinian processes in accounting for the diversity we see in biology. In addition, Gauger shares her journey into researching human origins. After being asked to evaluate the scientific case against Adam and Eve, she dove into population genetics to see if monogenesis — the hypothesis that all humans are descended from two first parents — was even a possibility. What she discovered may surprise you. Don’t miss this review of Dr. Gauger’s fascinating and important research. Download the podcast or listen to it Here.
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