[00:00:00] Speaker A: Foreign the Future, a podcast about evolution and intelligent Design.
[00:00:11] Speaker B: Welcome to ID the Future. I'm your host, Andrew McDermott. Today we're kicking off a series of episodes exploring the origin and design of one of the most significant innovations in the history of life, the eukaryotic cell cycle. We're going to discuss why evolutionary processes cannot account for the abrupt transition between prokaryotic and eukaryotic cell division, and why intelligent design is a more satisfactory explanation. My guest is Dr. Jonathan McClatchy, a fellow and resident biologist at the Discovery Institute's center for Science and Culture. He was previously an assistant professor at Sattler College in Boston, where he lectured biology for four years. McClatchy holds a bachelor's degree in forensic biology, a master's degree in evolutionary biology, a second master's in medical and molecular bioscience, and a PhD in evolutionary biology. His research interests include the scientific evidence of design in nature, arguments for the existence of God, and New Testament scholarship. Jonathan is founder and director of talkaboutdoubts.com welcome Jonathan.
[00:01:18] Speaker A: Great to be here. Thanks so much for having me.
[00:01:20] Speaker B: You're welcome. Well, you've long been interested in the origins of the eukaryotic cell division cycle. You've published several articles about it at evolutionnews.org, our flagship news and commentary site that covers the debate over evolution and the evidence for intelligent design. In those posts, you detail the exquisite engineering and design that's manifested by the cycle and its control systems. You also just published a paper on the topic at Bio Complexity. Congratulations on getting that out.
[00:01:49] Speaker A: Thank you.
[00:01:50] Speaker B: So, across four episodes, we're going to unpack your work on the eukaryotic cell cycle so we can really wrap our heads around how the system exhibits irreducible complexity and why it's so implausible to suggest that a gradual, stepwise evolutionary process produced it. Let's start with a few basics just to get us in the game today. What are prokaryotes and eukaryotes, and what are some of the key differences between the two domains of life?
[00:02:18] Speaker A: Sure. So the primary difference between a eukaryotic cell and a prokaryotic cell is that a eukaryotic cell has a nucleus, whereas a prokaryotic cell does not. Eukaryotic cells also have membrane bound or membrane enclosed organelles like mitochondria or chloroplasts, for example, whereas prokaryotic cells don't. They also have fundamentally different forms of cell division. So eukaryotic cells divide by mitosis Whereas prokaryotic cells divide by binary fission.
And there are some other differences as well. The composition of the cell membrane, for example, in bacteria the membrane is comprised of peptidoglycan, whereas in eukaryotes it's a phospholipid bilayer. But so there's a number of differences between the prokaryotic cell and the eukaryotic cell.
[00:03:07] Speaker B: Okay. And it's generally assumed that prokaryotes came first. Right. And eukaryotes evolved from there. Is that right? Is that the general understanding?
[00:03:18] Speaker A: That's correct. And it's thought generally that the eukaryotic cell emerged from a fusion event between an archaeal cell and a bacterial cell. The archaeal cell, having engulfed the bacterial cell and the bacterial cell, give rise to, to the mitochondrion. Mitochondria is plural, mitochondrion. And this energized the, the origins of the eukaryotic cell. The chloroplasts are also thought to have derived from bacterial endosibillance as well. That's, that's the general thinking.
[00:03:50] Speaker B: Yeah. And this is part of the evolutionary story that you just don't buy and that you have real doubts about. And so we're going to explore that over some episodes here. Well, there are multiple phases in eukaryotic cell division, from the first step interphase to the last cytokinesis. Can you review those for us?
[00:04:10] Speaker A: Absolutely. So, as you said, the cardiac cell is divided into four phases which we designate G1, S, G2 and M. G1 and G2 stand for growth phase one, growth phase two, sometimes called gap phases.
S stands for synthesis. And it's basically the phase of cell division where the DNA replicates in preparation for the cell to divide. And then the culmination of the eukaryotic cell cycle is M phase, which stands for mitosis.
And collectively the G1, S and G2 phases are referred to as interphase. And that takes up approximately 90% of the cell's lifespan. So the gap phase one or G1 phase is period of cell growth that occurs prior to chromosome duplication. And during the G1 phase, the cells are able to exit from the cycle and enter a non dividing state called G0. Or they might pass a so called restriction point which commits them to the entire cell cycle. And that irreversible decision is largely dependent on the availability of nutrients and often the cell size. So for many types of cells, commitment to another round of division requires a critical cell size. And there are external factors that are known as growth factors that play an important role in the regulation of the transition past that restriction point. So many human cells, such as neurocells, are permanently arrested in the G0 state and others can be induced to reenter the cell cycle, while others, like skin cells, are constantly dividing. And cells that are in the G0 state have elevated concentrations of cell cycle inhibitors and are characterized by an absence of DNA replication enzymes. Cells in the G1 state, on the other hand, are marked by low concentrations of cell cycle inhibitors and the presence of DNA replication enzymes. So as I mentioned before, the S phase or synthesis phase is a stage at which DNA replication occurs and that produces two sister chromatids which are identical copies of each chromosome. And these sister chromatids are tethered together by a protein known as cohesin until mitosis occurs.
And there are complex regulatory mechanisms that ensure that the DNA is replicated completely inaccurately before the cell is allowed to enter the next phase of the cell cycle. And the the DNA replication process itself, as we've discussed previously on this show, is absolutely astounding process involves many different specialized protein complexes and I've written a number of essays Evolution News, on the subject as well. So the growth phase two, or the gap phase two, G2 phase, is a second phase of growth prior to the separation of the cystoch chromatid. So during that phase, the mitotic spindle, which is the apparatus responsible for driving chromosome segregation, begins to form. The cellular content increases further as well, and that content will later be distributed between the two daughter cells and there's a cell cycle checkpoint.
And cell cycle progression can be temporarily arrested or paused if there is any chromosome damage, such as a double stranded DNA break, until the damage is repaired. So that's what we call the DNA damage checkpoint. And then the culmination of the eukaryotic cell cycle is M phase, which is the final phase of the cell division cycle. And during that phase there are two major events. There is mitosis, which, which is the basically the process by which the sister chromatids are segregated into the opposite sides of the cell, which is followed by cytokinesis, which is a division of the cell to produce the two new daughter cells.
So the chromatids attached to the mitotic spindle, which is made up of composed of microtubules that radiate from organelles called centrosomes, which are also known as microtubule organizing centers, and these kinetochores which radiate from these centrosomes bind to the Kinetochore, which is a complex of proteins that is assembled around the centromere of each chromosome. And the mitotic spindle pulls the sister chromatids apart, creating two identical chromosome clusters, which will go on to populate the two resultant daughter cells. And there are also checkpoints in place to halt the cell cycle progression if there are any problems, such as chromosomal segregation or improper attachment of the chromosomes to the spindle. This is known as the spindle assembly checkpoint, which we can discuss in more detail in a later episode. But so. So that's basically a summary of the different phases of the cell division cycle in eukaryotes.
[00:09:12] Speaker B: Yeah, a very complex process occurring over multiple steps.
And, you know, this is a good time to remind listeners that you don't need to be afraid of the complexity that Jonathan is. Jonathan is drawing us into here. You know, as Marcos Eberlin has put it, you know, we want to dip a toe in this complexity, in this ingenuity, this ocean of ingenuity, as he calls it. And Michael Behe has challenged us to bite the bullet of complexity. You know, if you really want to understand why evolutionary processes cannot do this, we've got to jump in. And as usual, Jonathan is game for helping us jump into that ocean of complexity, even for a few minutes. Okay, well, Jonathan, the last stage in cell division is mitosis. So tell us specifically how that plays a role here.
[00:10:03] Speaker A: Sure. So there are several different mitotic stages, right? So these are known as prophase, prometaphase, metaphase, anaphase, and telophase. And then, of course, the culmination is cytokinesis, which is part of M phase, but not strictly part of mitosis. So prophase, the chromatin condenses into the chromosome structures that we're all familiar with, in which the chromatin becomes visible under the microscope. So if you've ever taken even a high school biology class, you might have seen these chromosome structures under a microscope or seen them in a textbook, at least. And during interphase, the chromosomes are very decondensed, whereas during M phase, chromosomes take on that condensed structure, so that's prophase. And then during prometaphase, the nuclear membrane disintegrates and breaks into membrane vesicles, and the kinetochores form during that stage and become attached to the microtubules that radiate from the centrosomes at the spindle poles. And then during metaphase, the condensed chromosomes line up in the middle of the cell, sometimes called the equatorial plane. Of the cell, driven by motor proteins kinesin and dynein that are associated with the microtubules. And then during anaphase, the chromosomes break up and sister chromatids are pooled to the opposite poles of the cell. And then finally, during telophase, which occurs at the same time as cytokinesis, two daughter nuclei are formed and the chromosomes unravel back into their original expanded chromatin formation.
[00:11:42] Speaker B: Okay, all right, so that's mitosis in a nutshell. Now you write that various components of the mitotic cell division apparatus are indispensable for the system to work. This makes the eukaryotic cell division irreducibly complex, rendering it resistant to explanations in terms of blind evolutionary processes. As you note in your articles, any system that achieves a complex, higher level objective by means of various well matched interacting components requires foresight to come about.
So let's zoom into some of the components that make this system irreducibly complex. First, we have condensents. What are they and why are they important to the process of eukaryotic cell division? Sure.
[00:12:25] Speaker A: So condensents are these protein complexes that play a very important role in the organization and indeed in the segregation of chromosomes during cell division. And they're highly conserved across eukaryotes, so they're found across the the taxonomic board, if you will. And so condensin 1 is active during late prophase, and it contributes to the structural integrity of chromosomes following the breakdown of the nuclear envelope. And then condensin two functions earlier in prophase and is involved in the initial stages of chromosome condensation in the nucleus. So the condensin molecules are composed of five subunits, including the smc, which stands for structural maintenance of chromosomes proteins. You've got SMC2 and SMC4, which possess ATPase activity. So SMC proteins possess coiled coil domains, which are long flexible arms that fall back on themselves that create a V shaped structure, A hinge domain that facilitates the demorization of the two SMC proteins, and head domains contain ATP binding and ATPase sites that energize the activities of the condensins.
And then, as well as the SMC subunits, there's also three non SMC subunits, which bind specific regions of DNA and assist in regulation of condensin activity.
So the condensin complexes load onto chromatin in a stepwise manner, and that's directed by the non SMC subunits. The SMC subunits create loops in the DNA that use their ATPase activity and these loops are stabilized and condensed into mitotic chromosomes and then the condensed. So the condensed proteins are crucial for the process of cell division.
So without them, the consequence would be quite disastrous. You would have chromosomal disorganization as well as great difficulty in achieving proper segregation during mitosis.
[00:14:29] Speaker B: Mm. Okay. Now, another complex of proteins known as the kinetochore, plays a crucial role in ensuring the equal distribution of genetic material. Tell us about kinetochores.
[00:14:40] Speaker A: Sure. So, as I mentioned earlier, kinetochores assemble around the centromere of each chromosome, and they are critical to the process of mitotic cell division. So each kinetochore serves as an attachment site for the spindle microtubules, which radiate from the centrosomes at the cell's poles. And they assist with the alignment of chromosomes at the equatorial plane, the midpoint of the cell during metaphase. And this makes sure that there is an equal distribution of genetic material. So kinetic cores are also able to sense tension generated by the microtubule pooling. And this, this contributes to proper attachment.
[00:15:22] Speaker B: Okay.
[00:15:23] Speaker A: And so if you have improper attachment, for example, if the kinetochores of both sister chromatids are attached to the same pole, then these errors can be corrected by the kinetochore associated machinery. So if you didn't have the kinetochores, it would result in the improper attachment of the chromosomes to the spindle apparatus, and the genetic material would be unequally distributed to the daughter cells. And so the kinetochores are pretty crucial to the whole process of cell division. In fact, they are also found ubiquitously throughout all known eukaryotic organisms. There are no exceptions.
[00:15:55] Speaker B: Okay. And the key with calling it irreducible, irreducibly complex is that you pull out any one of these components and it's not going to work. Right. You're not going to have successful cell division. Well, what about separates and the anaphase promoting complex? How do. How do those ensure the success of this?
[00:16:15] Speaker A: Sure. So progression from metaphase to anaphase is mediated by the anaphase modeling complex, or cyclosome is usually called for short, the apcc, apc, and then the slash C for anaphase immunocomplex or cyclosome, which is an E3 ubiquitin ligase. So it basically functions to attach ubiquitin peptides to substrates to tag them for degradation by the cell's proteasome, which is basically the cell's shredder. And so it's activated by its CO activator known as CDC20. And when it's bound to CDC20, it the polyubiquitylase so attaches multiple ubiquitin peptides to securin, which is a protein that prevents the cleavage of cohesin by the enzyme separase.
So when securin is ubiquitylated, it's targeted for degradation by the cell's proteasome, and that liberates the enzyme separase to cleave the cohesin ring that tethers the sister chromatids together and that promotes sister chromatid separation. Okay, so if separase were missing, then the sister chromatids would fail to separate and the cell would be rendered unable to segregate its chromosomes at anaphase. In fact, experimental knockout studies have shown that deleting separase results in embryonic lethality. So the embryo dies, and cell cycle progression would also be halted in the absence of the anaphase morden complex, inhibiting the progression from anaphase to anaphase. And in fact, experimental studies that knocked out APC2, which is a core subunit of the anaphase mitten complex in mice, has resulted in lethal bone marrow failure within only seven days.
[00:17:57] Speaker B: Wow. Okay. So lethality can definitely occur without the help of some of these components here.
Wow.
[00:18:05] Speaker A: Absolutely right.
[00:18:06] Speaker B: Well, what about Aurora kinases? This is another component. What are those? Tell us about those.
[00:18:12] Speaker A: Sure. So aurorakinases are also crucial to proper spindle formation and chromosome segregation. So, for example, there's orokinase A, B, and C. So, for instance, orokinase A serves to phosphorylate proteins involved in microtubule organization, and it facilitates the accurate attachment of microtubules to kinetochores. In fact, an experimental study has shown that that Aurora A null mice die early during embryonic development during the 16 cell stage. And these Aurora anal embryos have defects in mitosis, particularly in spindle assembly. And this provides evidence of the crucial nature of Aurora A during mitotic transitions. And so this indicates again, that Aurora kinase A is among the components that are essential for successful cell division. So the activity of Aurora kinases is really important.
[00:19:14] Speaker B: And what would eukaryotic cell division look like without the help of microtubules?
[00:19:20] Speaker A: Well, microtubules, as I already mentioned, radiate from the centrosomes and anchor to the kinetochore complex, which is assembled around the centromere each chromosome. And during metaphase, as I mentioned, the chromosomes are aligned along the midpoint of the cell, the equatorial plane, and they are bound by these microtubules, also known as spindle fibers, at the kinetochore. And then in anaphase, the stage after metaphase, the sister chromatids get pulled apart by the microtubules, and this is driven by polar spindle forces.
So the microtubules are absolutely essential for segregating cystochromatids into two daughter cells. And so if you didn't have the microtubules, then the mitotic spindle assembly would be severely impaired, and this would inhibit the chromosome alignment and segregation. In fact, experimental studies that have been conducted with mouse embryos that are deficient in gamma tubulin exhibit mitotic arrest that arrests development at the moroblastocyst stages.
[00:20:23] Speaker B: Okay, now I want to mention one more component here as we're introducing all this and looking at the irreducible complexity of this system. What about the contractile ring? Tell us about that.
[00:20:36] Speaker A: Sure. So the contractile ring plays an important part towards the end of the cell division cycle in the process, specifically of cytokinesis, which is the culmination of M phase, where the cell physically divides into two daughter cells.
It's composed of actin filaments and myosin T motor proteins, together with other regulatory proteins such as foramens, rhoa and septens. And these components form a dynamic belt like structure beneath the membrane at the equator of the dividing cell. The contractile ring produces a force that's needed for the ingression of the cleavage furrow. Myosin 2 proteins interact with actin filaments in the ring to generate the contractile force. And this process is energized by hydrolysis of ATP. And as the ring tightens, the plasma membrane is pinched inward, and this ultimately divides the cytoplasm. And so if you didn't have the contractile ring, then there would be a failure of the cell to divide, and it would lead to binucleated cells as well as other abnormalities. So, again, the contractile ring is absolutely crucial to this whole process.
[00:21:43] Speaker B: Yeah. Now, there's a lot more we could bring up here, but we have a few episodes to unpack all this. So in separate conversations, we'll discuss motor proteins and the various checkpoints that are essential in this process. We'll also dedicate a whole episode to discussing the disparity between the cell division processes of prokaryotes and eukaryotes and why that poses such a challenge for Darwinian processes.
I want to continue. Well, actually, just conclude this introduction by mentioning something you brought up in your New paper on this topic. You note that in his famous book on the Origin of Species, Charles Darwin uses the Latin expression natura non facit saltus, which translates to nature does not make jumps.
Now, I haven't come across this before, and I really like that expression because it kind of illustrates the built in limitation of Darwinian processes. By default, they are stepwise and gradual. And of course, Darwin himself acknowledged this test of evolution in the Origin. He said, if it could be demonstrated that any complex organ existed which not could not possibly have been formed by numerous successive slight modifications, my theory would absolutely break down. Now, Jonathan, the system we're discussing today and all the systems we're unpacking in our ongoing series together on the podcast, are those the complex organs and systems that, that help to break down Darwin's theory?
[00:23:11] Speaker A: Absolutely. And it's the norm rather than the exception? Pretty much. I mean, there are hundreds or thousands of examples in biology of iridescent complex systems. And as we'll see in a future episode, there's a wide gulf between the prokaryotic cell division machinery and the eukaryotic cell division machinery. There's essentially nothing in common either in terms of the protein components that are involved or the underlying logic.
And there's no trace of homologues of eukaryotic cell division proteins among prokaryotes, for the most part, the vast majority of proteins that are involved in mitotic cell division in eukaryotes, you cannot find homologues of them among prokaryotes, including in the archaea, which are believed to be closer related to eukaryotes than our bacteria. They're just not there. And so how do you assemble such a system that requires multiple well matched interacting parts in order to achieve the higher level objective? How do you achieve such a system without knowing what the target is? By virtue of numerous successive slight modifications? And in particular, when we're talking about cell division, which is absolutely crucial for differential survival, how do you accomplish that transition from binary fission that we find in prokaryotes to the world of mitosis without passing through any maladaptive intermediate steps? And so that's, I think, a real hurdle to the evolutionary process, and I think it's far better explained on a design framework.
[00:24:41] Speaker B: Yeah. Well, I am looking forward to unpacking this topic in more detail with you over the next few episodes of our little series here. And I can't think of anybody who has studied this in more detail that's in my network, of course, than you. So thank you for joining us. Today, Jonathan, and beginning this series.
[00:25:01] Speaker A: Thank you. Great to be here.
[00:25:03] Speaker B: Now we'll include links to Jonathan's new paper in Bio Complexity, as well as his relevant
[email protected] in the show notes for this episode. So hop over to idthefuture.com and you'll find the show notes for every single episode. And it's also in condensed form on YouTube where you can listen to the show as well.
You'll also find links to Jonathan's work at his website, jonathanmcclatchy.com jonathanmcclatchey.com well, again, thank you, Jonathan, and we shall see and talk to you again in the near future. For ID the Future, I'm Andrew McDermott. Thanks for listening.
[00:25:41] Speaker A: Visit us at idthefuture.com and intelligent design.org this program is copyright Discovery Institute and recorded by its center for Science and Culture.
