About the guest: Michael Lynch, PhD is an evolutionary biologist at Arizona State University who studies the origins of genomic and cellular complexity.
Episode summary: Nick and Dr. Lynch discuss: natural selection vs. genetic drift; genetic mutations & the speed of evolution; origin of life; the evolution of cellular complexity; epigenetics & the inheritance of acquired characteristics; and more.
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Episode transcript below.
Full AI-generated transcript below. Beware of typos & mistranslations!
Michael Lynch 3:45
Well, I'm currently a professor in Life Sciences here at Arizona State University. But I've gone through quite a trajectory. I almost went to med school, then accidentally found out about this thing called graduate school and went off and studied to become a monologist. That's a person who studies lakes, University of Minnesota and got into ecology their start starting to learn about application of models to biology for the first time. That was good because I was interested in mathematics as well. And went through graduate school kind of rapidly that a lot of fields were was getting a little bit uncomfortable with it with the generality the results we were getting were on community structure and lakes, then discovered population genetics and my last year I was able to sit in a nice course by Michael Simmons and the genetics department there. And lo and behold, then got a job. At University of Illinois I applied kind of early, I thought it might be hard for me to get a job. I applied kind of early and before I ever My thesis and got a job at Illinois and the ecology ethology and evolution department. Higher was in aquatic ecologist but then was able to gradually get into population genetics with system organisms we were working with a time daphnia micro crustacean, this is back in the very early days of population genetics, the whole field was almost entirely theory. But there were these new things called allozyme that had been discovered, that enabled us to separate proteins on shells and crudely figure out of different individuals are carrying different alleles that it all worked. The first time we applied it to daphnia and I. So I rather quickly moved into this new field, my department had at the time apparently didn't pay too much attention to Peter was happy for me to do any research I wanted, but I essentially shifted fields. And within the first five years, I was no longer doing limnology, but population genetics, and then just moved on to that field from there. Shortly thereafter, I moved to University of Oregon, to start a new group in ecology, and evolution, or first program and whole organism biology there. And I guess about a decade after that, that's when the age of genomic started. So in that transition, I was really working in the area of quantitative genetics, I learned a lot of the field at Illinois, from the animal breeders there. But then I was in the right place at the right time with people started sequencing genomes. And then we started seeing ways to connect evolutionary theory with genomics. Spent a while on that wrote a book on that topic on ideas of how I think genomic diversity developed across the tree of life. From there moved down to Indiana University that was about when the book got published, and continued working along many of the same lines I had worked on before. But a lot of people moved into the field of genomics, and I was sort of looking for things to do. And for me, the natural next step was to see if the ideas I had on genome evolution would extend to a higher level of organization. And at that time, the, the attraction was cell biology. And so, since about the, I guess, since around 2010, or so I've been focused on trying to help develop this new field of evolutionary cell biology. Of course, there's a really sophisticated field of cell biology out there with exquisite ly detailed measures and cellular structures and rates of reactions and so on. But it's really far removed from evolutionary biology. You the other hand, most of evolutionary biology pays no attention to what goes on inside cells. And so to me, the natural mechanisms that are relevant to understanding evolution must start at the cellular level, that's where all phenotypes are built. And so we're now trying to make this bridge this gap between evolutionary theory and diversity of cells within and among phylogenetic lineages. And as I moved Arizona State University, I started this whole new center called center for mechanisms of evolution. And that's more or less what we're focused on. We're sort of a group of misfits, from different areas of biology all focused on developing this new field.
Nick Jikomes 8:50
So I want to start off by just giving people a sense for what the tree of life actually looks like. So can you tell us a little bit about what the major branches of the tree of life are? And sort of how big and how diverse each one is? Like how, how diverse are bacteria compared to animals, multicellular organisms, and so on and so forth?
Michael Lynch 9:14
Well, the tree of life has undergone quite a transitions since I started at the University of Illinois, I was there at an optimal time actually. One of my colleagues was a guy named Carlos. And Carl figured out how to sequence RNAs and particular ribosomal RNAs and he used that to attempt to develop the first deep, branching form of the tree of life and, of course, discovered this big split between various prokaryotic lineages in particular one group that became known as the archaebacteria. And another at the time was known as the Eubacteria. And so Suddenly there's this two domain of life free. Before are all prokaryotes. We're just lumped into what was thought as one big phylogenetic group. Of course, this got, I should go back, I shouldn't call it the two domain of life, there were two domains of prokaryotes, the third domain, whereas eukaryotes, there's a big question and where the eukaryotic lineage fell in the tree, was it outside of all prokaryotes? I think that was the natural inclination initially, or was it derived from inside the bacteria or the archaea, was adobo, Zach, and so on. A lots changed since that this was a revolutionary finding the archaea, bacteria, of course. But now that we've sequencing whole genomes, and a much broader assessment than just the ribosomal RNAs, it's pretty clear that we eukaryotes are derived archaea. So now we've gone back to the two domain of life. The two domains are no longer though. Prokaryotes versus eukaryotes, it's the bacteria on one side of what we think is the root of the tree. And on the other side are the archaea. And essentially, we eukaryotes are derived Archaea were one branch within the Archaea lineage.
Nick Jikomes 11:25
Okay, so big picture. So at one point, we kind of thought, there's simple organisms like bacteria, and other complicated organisms that include us and some other things. And then eventually, we figured out there's actually two sort of completely different types of simple single celled organisms. And then there's the complex organisms. And we'll get into that a little bit in more detail later. But what we figured out it sounds like is that we didn't sort of evolve independently of those two, we sort of emerged, eukaryotes, complex organisms emerged from one of those types of simple bacteria.
Michael Lynch 12:01
Yeah, that's the prevailing idea. Now, and it looks pretty solid. It's fair to say we're on mosaic, though, in the sense that somewhere below the root of our key of eukaryotes, the Archaea lineage that led to us picked up endosymbiosis endosymbiotic, now called the mitochondria. And that endosymbiont was pretty clearly derived from bacteria. We've known that for quite a long time. I
Nick Jikomes 12:35
see. So one type of single celled organisms sort of absorbed, another completely different type. That's
Michael Lynch 12:40
right. And many of the genes inside the mitochondria were transferred to what is now the nuclear gene of eukaryotes. So we're really a mosaic of the two major prokaryotic domains of life in some sense, there's still some debate about, you know, the timing of events here, and so on. But this seems to be the really broad picture at this point in time.
Nick Jikomes 13:12
And so how so so you've got these sort of three big branches of life, two types of prokaryotes, which I'll just call simple organisms, and then you've got the branch of complex organisms called eukaryotes. how dense are each of these branches? Are there way more bacteria and simple organisms than there? Are eukaryotes and complex organisms like us? Or is it comparable? Or how do we start to assess that?
Michael Lynch 13:40
Well, that's a that's a good question. And it's partly unresolved, how dance that sort of is asking how many species there are, and so on. And we're getting more of a glimpse of that. Because we can do environmental sequencing of DNA where we don't even really look at the organism. Many, many prokaryotes are on cultivatable. I guess the bigger question is How deep are the branches, and the different domains and it's pretty clear now that the if you just think about the depth of all the branches and diversity in the entire tree of life, most of it is in fact prokaryotic. Even within, as I said, we're just one branch and the archaebacteria, which contains many, many deeply divided lineages. So we're one branch and one part of the one side of the root of the tree of life. Most of us eukaryotes are unicellular. And so there's many deep branches of unicellular eukaryotes. It's all the result of a quick radiation of the eukaryotic lineages. And then a small number of US decided to go down the route of multicellularity. metazoans are animals, of course, are the, one of the more prominent ones and land plants and other fungi to a certain extent. But us, animals are a very tiny part of the branch or the entire eukaryotic Tree of Life and mammals an even tinier speck on the tree. So we, you know, most biologists, even evolutionary biologists tend to study land plants and, and, well, vertebrates, I mean, there's quite a bit of invertebrate biology as well. But we're really studying only a very small portion of the entire tree of, of biological diversity, most of biological research is based on a very small fraction of the tree life.
Nick Jikomes 15:50
And so because it's so hard to cultivate, to just find life forms that are out there, there's, you know, probably a whole bunch of stuff we haven't discovered, do we have any sense for? How many, how much of the tree of life we've actually discovered? And how much is out there to be discovered?
Michael Lynch 16:09
Yeah, that's a really good question. mean, this whole idea of us being derived Archaea is only come about in the last 10 years. And that was a consequence of, of sampling, some, you know, deep sea samples, just doing what's called meta genomic sequencing. So just taking a lot of DNA out of a bottle of mud, and then sequencing to a high enough depth that you can actually start to construct the organisms or down or even the absence of any visual data on them. But you know, that's just one, you know, semi unusual environment, there's almost certainly other are maybe very substantial discoveries to be made. We still have uncertainty about what particular branch and the archaea, eukaryotes came out for this very reason. And we may eventually find particular lineages that are intermediate states between current archaea and eukaryotes. So this is the problem we have right now is most eukaryotic lineage that we've looked at, like everything was there. So mitosis was there, an internal organelles, and so on. And so this is big morphological gap between us and archaea. But it's not to say there are some, you know, deep Archaea lineages with intermediate phenotypes that might then help us understand the order of events. And the emergence of eukaryotes.
Nick Jikomes 17:55
Going back even deeper, when we think about, suddenly look at the diversity of life that we have uncovered, and we think about the origin of life, do we know pretty definitively there was one origin of life on Earth? Or what what do we actually know about the origin of life? Is that something we can figure out? Is it something that we know happened once, or at least once? Is it possible that some that multiple origins of life happened and then there was some kind of, you know, mixing of them? What do we know about about that root of the tree of life?
Michael Lynch 18:28
Well, there's a lot of things done back there. We think that, oh, current lineages that we're aware of go back to as a single origin that's based on a very small number of genes shared, you know, less than 100 genes that are shared among all organisms. We need that those genes, they provide the information on developing genealogies of shared and unique differences. So there's not a lot to go on there. There are a number of other issues here. One is that the way we replicate DNA we archaea, and US derived eukaryotes, replicate DNA is using machinery quite different than bacterial lineages use. So that's led Eugene Koonin and colleagues to suggest maybe replication mechanisms. And these two lineages today evolved independently. there very well could have been many other independent lineages of life that were going on at the time. There's this thing that we call Luca, the last universal common ancestor. That's the ancestor to all of us living organisms on Earth, could very well have been other lineages. that were around at the time that went extinct, it's unlikely we're ever going to be able to resolve that because DNA, you know, the remnants, the molecular fossils we need, are just not going to be there. We can't even formally rule out the possibility of life originated in another planet, and was transmitted to hear, hear by a comment, comment or so. So we've, we know that based on phylogenetic information, using molecular fossils and Gene genealogies that lifestart seems to have started very soon after the the earth originated, you know, close, getting very, very close back to 4 billion years. So things happen pretty quickly. And of course, at that time, we, well, the earliest forms of life would have been pre cellular, we're gonna have no information on that there's this whole hypothesis about an RNA world, Carl will always have this idea that early, the earliest form of life was sort of a, you know, almost kumbaya sort of community went through had all kinds of became very unclear what what an organism even was, under his view, and what a population was, and so on. But then eventually cellularity took hold. And now we've got independent lineages where individual genotypes are linked inside internal cell membranes. So there's a direct connection now, between genotype and phenotype. And inheritance from parent to offspring cell.
Nick Jikomes 21:45
What's the best estimate for when the first cell evolved?
Michael Lynch 21:52
Well, the latest estimates as alluding to, again, this is based on shared inheritance of this small number of genes that we all have. And making assumptions about what a thing we call the molecular clock. So we can measure divergence among phylogenetic lineages, we can do that, you know, there's X percent divergence, but we need to know how to translate that into time. How many changes occur per nucleotide site and a genome per unit time. So we have to use these calibrated molecular clocks. The latest estimates are pushing the root of the tree of life back to about four point 1 billion years. But it's getting very tight because we think the the earth originated about 4.4 billion years.
Nick Jikomes 22:52
Is it fair to say that over time, our understanding of the origins of our estimates of the origin of life have gotten closer and closer to the the origins of the earth? In other words, that life emerged more quickly than we used to think.
Michael Lynch 23:04
Yeah, these molecular estimates are pushing things back farther, there are quite convincing fossils. We don't know what they are. But we're pretty convinced they're biological. Certainly go back to 3.8 billion, so that much, we're sure. But now the molecular data are pushing things back even further.
Nick Jikomes 23:29
And, you know, going back, so you said there's these about 100 genes that that are sort of common to all life forms? What are those genes encoding? That's related to the question of what are sort of the universal features that all forms of cellular life share? What what are the structures and the cellular functions that they're all doing that? Are that that core set of things?
Michael Lynch 23:53
Well, the core set of biology, you know, what is biology made up, like, what's the basic biology all organism have is pretty broad. But over time, there been what we call known orthologous, Gene replacements and so on. So the same function that's in a certain lineage won't necessarily be carried out by the same gene. And there have been probably de novo origins of different genes and so on. So there are a lot of functions that we share, you know, things like you know, the Krebs cycle, we all make lipids to produce membranes glycolysis you know, things that go back very deep, all the translation machinery, as I just pointed out, you know, the transport, or sorry, the replication machinery is quite different. The translation machinery, the ribosomes that goes back all the way, that's why Carl was using ribosomal RNA to really look at the entire tree of life. The ribosome itself is bizarrely Complex. organelle their hands on what lineage but there's on the order of 100 proteins wrapped around the ribosomal RNA, some of those proteins seem to be shared by everybody. So this
Nick Jikomes 25:12
is this is the protein, the protein structure in cells that takes genetic material and transforms it into proteins. Parts of this go back all the way as far as we can tell, that's what you're saying.
Michael Lynch 25:24
Yeah. Yeah. So we, we really had other some bizarre features of biology, you know, rehab genomes made up DNA. That's where the messages are. That's where the, you know, the vocabulary is to produce proteins. But the DNA has to be translated, transcribed into these things we call messenger RNAs, that's RNA. The RNA then has to be read by the ribosomes. That translates codons, which are each three nucleotides long, each one stands for a particular amino acid. And then there's a stop codon. Three of them are stop codons. We have triplets or stops. The ribosome works together with things called transfer RNA that bring in an amino acid that then links to the anticodon, that then reads off the codon. So all biology has t RNAs, and ribosomes. So those are example things that go all the way back.
Nick Jikomes 26:32
And I suppose that's why people have ideas about this RNA world that that RNA and proteins were there before DNA came into the mix?
Michael Lynch 26:42
Well, that's a good question. Did proteins come before DNA or or vice versa? There's a strong feeling that RNAs had to bend around early on. The fact that transfer RNAs are made out of RNA and ribosomes are made out of RNA suggests that there must have been some code early on whether that code itself the genome itself, that was being read off was also RNA, or and then there was a later DNA takeover is, is a bit unclear. But given there was a code, then seems likely there were amino acids doing something. Right, because the code is for the readout of amino acids. You know, whether they were being read out to make the kinds of complex proteins that we have today is another question as well.
Nick Jikomes 27:51
And so I think you hinted at this, how diverse is cellular metabolism are their core features of metabolism that are shared across the tree of life in terms of how we're generating ATP and in making energy for the cell?
Michael Lynch 28:06
Yeah, there are certain ones where you have one would be making ATP. We have this bizarre molecular machine called ATP synthase. We all use this by all I mean everybody across the tree of life. It's a turbine that sits in membranes of bacteria and archaea. We pump out hydrogen we well we produce hydrogen ions from organic compounds that goes through a shared set of machinery called the electron transport chain. That also sits in membranes of prokaryotic cells. That leads to the pumping out of hydrogen ions outside the cell membrane that that produces a hydrogen ion gradient. A proton protons are hydrogen ions. Those protons then go back through this molecular turbine called ATP synthase, twirling it around. And in that process, ADP is converted to ATP. So this is a I find this one of the most bizarre aspects of all biology, essentially, you know, think about building a dam on a river for a hydroelectric plant, and normally we check the river to make sure there's water in it before you build the dam and then the water just naturally comes down, goes through the turbine and makes electricity Well, ATP synthase is sort of like building a dam and then realizing oops, where there's no water above the dam. You gotta get the water out, you know? Our water in the case of ATP synthase is proton gradient, but we have to pump that out outside of bacterial cells. So that naturally comes flows back in through ATP synthase. I
Nick Jikomes 30:11
see Well, that imply that the original cell, maybe it needed to exist somewhere where such a gradient was already present in the external environment.
Michael Lynch 30:22
Yeah, that's the idea. It's a it's one idea. It's a hint that, you know, why are we using a proton gradient? Where did that come from? Well, maybe because the original form of life was sort of naturally exposed to some kind of proton gradient. One ideas that might have happened around hydrothermal vents, where, you know, geology is just naturally producing a gradient. That's, that's a really attractive idea, because now you've got a non biological, long, sustaining force producing sort of a gradient. There's a big step between that gradient and producing the molecular machine that we use today.
Nick Jikomes 31:11
I see. Okay, so that that would be that would be why, one idea is, is that these deep sea events could be a site of the origin of life.
Michael Lynch 31:20
Yeah, that's one proposed location. To think about these things, and just found the basis of the peculiarities of biology today, are these remnants telling us something about where life originated? Why did we certain metals in ourselves, you know, only a handful of them and not others, and so on. So
Nick Jikomes 31:41
all life uses ATP for energy? There's no, you know, there's a lot of probably variation, on top of that, in terms of, you know, you know, obviously, you've got plants using photosynthesis. And you know, animals, you know, making the ATP from different sources. But they're all using ATP. They're all using this turbine, this molecular machinery that relies on this proton gradient, that's a universal,
Michael Lynch 32:03
that's a universal so that, that goes back to this thing we call Luca. So that would be another example of certain set of shared proteins that we all have.
Nick Jikomes 32:19
So once I've got started, obviously, you know, it's there. And then it starts to diversify over time. That's the process of evolution that we're going to talk about. I want to start with some, some just basics here on some of the basic principles of evolution. So when we talk about evolution, typically people are thinking in terms of evolution by natural selection. So there's some natural diversity that's just produced intrinsically from the way that biology works. And individuals in a population are going to vary some way or another. And some of them will do better in a given environment. And that environment is sort of selecting them. And that's the process of natural selection. Can you just define for us? What is natural selection? And is that is that the only thing that explains the diversity that we see in biology or even the main thing?
Michael Lynch 33:08
Yeah, so you did a pretty good, provide a pretty good definition of natural selection. You know, I view natural selection is most powerful, one of the most powerful forces in the biological world, if you have very variation. And that variation exists at the genetic level, and can be inherited from parent to offspring, and it's related to differences in fitness among individuals, then natural selection will occur. The bigger question is how powerful selection is it's not all powerful. And natural selection can only promote certain changes that are significant enough at the level of fitness differences. In association with the phenotypic changes, that's what natural selection can do. But many mutations have very, very tiny effects. And in certain lineages of organisms, those effects are small enough that selection can grab onto them and push them on to the next generation. This gets into the whole idea of noise and the evolutionary process. So all would work fine. And natural selection would be a capable almost anything of populations for we're infinite in size, and everything was deterministic. But nothing in biology is deterministic populations are finite and size. There's a lot of noise due to the fact that a mutation arises here and oops, another bad one arises linked right next to it. That's no longer has a net selective advantage and so on. So there's this noise in the evolutionary process we call drift, random genetic drift. And if that level of noise is high enough so that the magnitude of fluctuations in allele gene frequencies from generation by the noise process, that that exceeds the deterministic push by natural selection, then drift winds, sort of there's this sort of fine point where we call this the direct barrier, there's this fine point where the two forces are essentially equivalent. If you go over to one edge far enough, and selection wins. If you go over to the other edge far enough, then random genetic drift wins. And we think, especially at the genomic level, drift wins in many, many cases in certain phylogenetic lineages.
Nick Jikomes 35:45
So if I'm understanding you, the bigger the population is, the more individual in the population, the easier it is for natural selection to act in the way that we normally think about it for it to push changes, quote, unquote, on purpose into the next generation, because they have better fit, they're better better match the environment. But the smaller the population, the more likely it is for this noise to dominate. And for natural selection, not to be able to work so well. And so I would imagine that as you sort of go from one branch or the tree of life to another, as you go from something like E. coli or simple organisms that have very, very large populations to something like us, you know, even even though there's, you know, a few billion people on Earth, that's still probably pales in comparison to the population of E. coli, you know, swimming around out there, that would mean that this sort of drift dominates in the sort of the physically bigger organisms because they have smaller populations.
Michael Lynch 36:45
Yeah, that's a pretty good description. And then there's a negative relationship between the size of an organism and its population size. That's certainly true. And bacterial populations are literally astronomical. In number. It's a little more complicated than that. That something I was alluding to is that the only determinant of the magnitude of drift is not just numbers of individuals. It's also the fact that our genes are tied together on chromosomes. And this causes selective interference. So the organisms could be genomes could be constructed in such a way that every nucleotide or separate than natural selection could operate and each nucleotide in a separate way, but we're all linked together on genotypes, and that causes what's called selective interference.
Nick Jikomes 37:45
I see. So so if I get a mutation that's in a gene on one chromosome, and it makes me better at surviving in some way. But then I have another mutation on the same chromosome in a different gene. And that makes me worse, those things can cancel out, because I can't I have to inherit that whole chromosome all at once. Yeah,
Michael Lynch 38:03
that's, that's one thing that can go on. That's called selective interference. Another kind of selective interference, it's very, very broad based, as far as we know, that occurs in all organisms related the fact that most mutations are deleterious. And so there's this constant rain of deleterious mutations coming down on all chromosomes and all organisms. And then those are being weeded out of the population. And when they're pulled out of the population, they pull out any linked genes with them. And so in a sense, you know, the population size can remain really large numerically. But genetically, it's behaving as though it's, it's quite small, because you have this persistent purging of variation that would otherwise be there are an enormous, physically enormous population.
Nick Jikomes 39:01
So if most, if most mutations are deleterious, and you're purging those from the population, this means that inevitably, you're going to be taking away new adaptations at some rate, even though they would be at a patient's because they're, they're tied to these deleterious mutations.
Michael Lynch 39:17
Yeah, in some sense. Yeah. So this becomes a really powerful for so you know, bacteria, you know, like an E. coli population has an effect what we call an effective population size, which is very different absolute, of only about a billion individuals. That's a very tiny pile of E. coli cells. But genetically, the population is behaving that way in a Gini illogical sense. Still, that's a lot of individuals. And that allows natural selection to be quite effective that can basically take advantage of mutations that have a an effect or Roughly one over the population size and effect small, the smallest 10 to the minus nine, and fitness.
Nick Jikomes 40:08
What about human beings? What What would? Do we know, humanity's effective population size?
Michael Lynch 40:13
Well, there's a lot of us on the planet today. But historically, the human population effective population size. You know, there's a lot of us today, but that wasn't true even 10,000 years ago. And historically, a human effective size is only about 10 to the fourth individuals. And you know, numbers like that are common for lots of vertebrates, and even some invertebrates. So
Nick Jikomes 40:41
similar words, even though there's billions of people walking around on the planet today, genetically the diversity we have looks like we're a population of 10s of 1000s. Yeah,
Michael Lynch 40:52
that's right. New diversity generated by mutation hasn't quite caught up, or what you would call out of equilibrium. But the point here is that these reductions in population size, especially in multicellular organisms, mean that natural natural selection is going to be more very more, much more coarse grained, that can only take advantage of mutations of relatively large effect, large enough to overcome the power of drift, whereas selection and bacteria can be very, very fine grained things can be very, very fine tuned over evolutionary time.
Nick Jikomes 41:33
And so is it so So can you give us so you said most mutations are deleterious? So you get a genetic mutation that can harm the organisms chance for survival? It could enhance the organism chance for survival? Or it could just be a wash, it could be neutral, somewhere in the middle? Can you give us a sense for how common each of those is? Like, are our adaptive mutations? Like very, very, very rare? Are there a lot of mutations that are sort of neutral? And they don't really matter so much? Or is everything just, you know, it's 99%? Of everything deleterious?
Michael Lynch 42:05
Yeah, that's a good question to that evolutionary geneticists are still struggling with we're trying to catalogue what what's called the distribution, fitness effects among all de novo mutations, what fraction are beneficial, what fraction are deleterious and of the beneficials? How many are so close to, you know, they're very, very slightly beneficial selection can take advantage of them. In generally, we think that only a small fraction are beneficial, maybe, maybe 1% or so mutations are beneficial, most are most are deleterious. And that's just the consequence of, you know, the eons of natural selection, refining, structures and functions in organisms so that most tweaks are going to make things worse. But, you know, things do move on when organisms are exposed to new adaptive challenges. When
Nick Jikomes 43:07
we think about when we look at animals and other creatures, and when we think about why they got to be the way they are, there's this natural tendency in evolutionary biology to think about things in adaptive terms. And we say like, Okay, this, this animal has got a really long tail, or it's got horns, or it's got this or that. We naturally want to think, Okay, why did that evolve in the sense of how did those things? How are those adaptations for the organism? How did it enhance the organism survival? But if the sort of neutral and random processes can be so strong, especially in relatively large organisms with small populations, what does that sort of tell us about like, how much of what we see in the tree of life actually evolved by natural selection is adaptive versus how much of it is just basically, you know, random or close to it?
Michael Lynch 44:00
Yeah, well, that's a broad issue that we're still struggling with. I guess, you know, one example would be genome architecture in different lineages. So bacteria, very, very streamlined genomes, there's there are almost 100% coding DNA, you know, 95%, plus very little excess DNA between genes and so on. And then you move into eukaryotes, you know, a lot of excess DNA and between genes. Our genes are split up by things called introns. So our coding DNA are actually islands in a sea of intronic DNA that actually gets transcribed but then has to be spliced out, or to make a productive messenger RNA by a machine called the spliceosome. bacteria don't have these kinds of introns. They don't have this kind of problem. Our genomes, especially in animals, and land plants are just littered with what are called mobile genetic elements, or some people call them jumping genes, transposable elements. The human genome has only about 1.5% coding DNA. So how did we get here? And why is it such a mess in US multicellular lineages and eukaryotes in general, good bacteria. The idea is a consequence of a reduction in effective population size is one the eukaryotic domain started to emerge and further reductions in multicellular lineages that made it easier for these genomic changes to accumulate in effectively neutral fashion. So,
Nick Jikomes 45:52
so if I'm hearing you correctly, basically, we when we compare simple organisms, like prokaryotes to complicated organisms, like eukaryotes, one of the things that what we mean by complexity, in one way is genomic complexity. So we've got, we've got more stuff, there are more features to our genes. It's not just purely chunk of DNA coding protein, there's a bunch of stuff in the middle, like the introns. And there's non coding elements that you mentioned. So I guess in principle, there's two ways you could start to think about that one would be okay, all this complexity must be doing something it must be buying us something it's been selected in, because there's an advant advantage to having all that extra stuff. The other way to think about it would be that it's a, because the populations are smaller, and these types of organisms, this stuff just accumulates passively, because selection can't really fine tune things and get rid of it. And it sounds like you're saying that a lot of it can be explained in that way, that it's just the natural passive accumulation of stuff based on population size.
Michael Lynch 46:59
Yeah, that's basically my my view of all this, it's a passive expansion of excess DNA in in genomes. Now, you know, if the mutation bias was for deletions, things would go the other way. And in sufficiently small populations, you're just being pushed by mutation pressure. And for mobile, genetic, genetic elements, they have a built in mutation pressure, there are copies of DNA selfish DNA that can make offspring of themselves in certain large chunks and other regions of the genome. So that's why we're biased towards large size. But there is an interesting point to be made here is that there's a, we should make a distinction between the origins of alterations in something like genome architecture or any other feature of an organism, which could be bad passive, completely passive mechanisms, not advanced by adaptive mechanisms. But now you have sort of changed the genomic real estate. And you have, you know, different kinds of material upon which natural selection might operate wasn't there before. A good example of this would be introns. As I said, our genes are in our eukaryotic genes are in pieces. And in us, multicellular species, the coding DNA, our little tiny islands separated by these early large introns. And in multicellular lineages, these have become useful because it's possible to differentially splice out introns. So you can have alternative tissue specific splicing of genes. And you can make different variants of genes that might work in one way in one tissue and be utilized in another way in a different tissue. So that's a that's a way of thinking about how introns might be advantageous in certain lineages and multicellular organism in different tissues, for example, but introns evolved at the root of eukaryotes before there were multicellular organisms. So you can't invoke, you know, tissue specific alternative splicing as the mechanism that you know, promoted intron evolution by natural selection that came later.
Nick Jikomes 49:32
I see. So, it sounds like basically, due to the interaction between drift and selection and the population size, you can get these increases in genome size and complexity by completely passive means it just sort of naturally accumulates over time. But in doing that, you're sort of creating a richer, more diverse substrate upon which selection can subsequently act. So you can take advantage of some of this complexity that emerges passive Li, and they'll do things that couldn't have done before. Before to merged.
Michael Lynch 50:04
Yeah. But you're going down a certain pathway that was developed by a non adaptive mechanisms. That's a lot of what biology is all about is, you know, historical events that, you know, sat us down a certain course forever, such as ATP synthase, you know, a bizarre way for us to produce energy. But that was the state of affairs and last universal common ancestor. And there's, there's no way going back anymore. Same thing with the ribosomes.
Nick Jikomes 50:36
What does it say about the the reproducibility or predictability of the evolutionary process? So for example, if you go back to the origin of life, or you go back to the origin of the eukaryotes, or you go back to the origin of animals, and then you let things play forward and time again, for 500 million years, or whatever, would you see similar things play out? Or could it be completely different from that starting point?
Michael Lynch 51:01
Well, I don't know. I'm capable of that kind of crystal gazing, but
I mean, there's a lot of a lot of other events, the worry about here, because, you know, it's, you know, it's the earth geological history to that has played played a role here. So I, you know, it's that's a very difficult question to answer. But, you know, drift is a chance process. And there have been historically contingencies where, for whatever reason, certain kinds of changes arose, and an ancestor to very, very large groups of organisms, for some vital functions that can never be lost. So in that sense, there can be these ratchet like effects. Many of those, I think, would probably be unpredictable in certain geological contexts, not knowing the particular settings.
Nick Jikomes 52:02
Okay, but it sounds like there's, there's a quite a large role for pure chance here.
Michael Lynch 52:08
Yeah, well, that's what I would certainly say, Sure.
Nick Jikomes 52:13
When we think about the evolution of complexity, and we think about the evolution of bigger cells, bigger genomes, going from unicellular clarity to multicellularity, can you give us a sense for? So when we think about what a cell is doing, it's transcribing DNA, it's translating proteins, it's creating gradients of ions, it's, it's doing all sorts of stuff, all that stuff costs, something that can you know, in that cost can be measured in ATP. So certain things can be done efficiently or cheaply, certain things are more expensive, you know, among the core functions of a cell, what are the sort of most important things energetically in terms of is the most expensive thing? So what are the most energetically costly functions of the cell? And how does that start to constrain or influence the evolvability of those things?
Michael Lynch 53:05
Yeah, this is something we're just starting to work on. So we can now catalog you know how much it cost to make each of the 20 amino acids, each of the four nucleotides, lipids, and so on. So we have a catalogue of things like that, and then cost some energy to, you know, glue amino acids together and make a protein and so on. So we have a pretty good sense now how to calculate the cost of making various parts of cells. And so we're, we're trying to merge this field of what's called bioenergetics. Now with evolutionary cell biology to get at these very questions, some of the things that are quite expensive are lipids, lipids are energetically, much more expensive, takes much more ATP to make a lipid than it does to make a amino acid or a nucleotide. Well, our main our cell membranes are made of lipids. So and our internal membranes and US eukaryotes are made of lipids. So we're eukaryotes are investing a lot in, you know, basic biological substrate lipids, that prokaryotes don't necessarily invest in. Now. We use those internal organelles for a lot of different things. But it's just one example. The mitochondrial lipid membranes are very, very expensive. So we have this thing we call the powerhouse of the eukaryotic cell, the mitochondria, and that's where we make energy. That's where our ATP synthesis. So before I alluded to ATP, synthase, being in the cell membrane, the plasma membrane of bacterial cells, it's not in our plasma membranes. It's in our mitochondrial intermembrane So that's why we make energy. But that little powerhouse of the cell is also pretty expensive to keep going. Because it's made out of a lot of lipids. And that's just sort of one example of what we're been able to start moving in this direction. unicellular lineages, swimming turns out to be a pretty high investment, it costs a lot to swim with flagella and the flagella themselves cost a lot, because they're made of long concatenations of proteins. So we're still at a very early stage of trying to figure out just what, you know, how is the the budget of the cell partitioned up. But basically, you know, the estimates we made, I like this one quite a bit, about 1/3 of the investment of cells, and it's an entire life history, from parent cell to baby cell, about 1/3 of the entire energy expenditure goes to making the cell membrane, and in bacteria also cell walls. If you, you know, if you buy a house, and talk to a realtor today, and ask them, you know, how much of my budget should I be spending on, you know, my mortgage bill, per month, and so on. And they'll tell you about a third of your salary. So, I find that quite interesting, because apparently, you know, the bugs are figured out, you know, that rough budget of Porsche nation themselves a long time ago.
Nick Jikomes 56:40
Wow. So a substantial fraction, about a third of the energy budget of a cell is going to constructing and maintaining lipid membranes? Yeah,
Michael Lynch 56:47
well, just the external housing. It's
Nick Jikomes 56:52
interesting, when you think about, like the different ways we can make ATP in our cells. So you've got like glycolysis, you've got, you know, just different different different ways of generating energy from different energetic substrates like dietary fats, dietary carbohydrates, are some of those more energetically efficient than others in terms of how much ATP we can produce. Like, is it more efficient to consume lipids than sugars or something like that?
Michael Lynch 57:21
Well, an individual, if you're breaking it down, I mean, it all ends up going through things like glycolysis. And this thing we call the TCA, or the Krebs cycle, I mean, an individual, as I said, an individual lipid molecule is more expensive to make in terms of the ATP is required to make it than say a glucose molecule would be. But that also means you can squeeze it contains more energy itself, so you can squeeze more energy out of it. So that's one way of looking at it in terms of, you know, dietary contributions to energy that can be extracted.
Nick Jikomes 58:05
Another phenomenon that's sort of interesting to me is called senescence. So cellular senescence, can you tell everyone what that is and where it comes from?
Michael Lynch 58:20
I don't know if I could just like that's one of the let's just start with to start with is a gradual breakdown in the P like the homeostatic mechanisms of the cell. But for single celled organisms, we don't know very much about this at all. You have to follow lineages of individuals to pick any app to know whose mom and whose offspring because you want to be thinking about the senescence of the maternal cell. And things there's a thing called budding yeast that, you know, 1000s of biologists work on and the baby is the bud that comes off so you keep track of the mother that way. And you know, single cell yeast do seem to synapse over time. population lives on because the babies are just like us humans. The babies are, in quotes, rejuvenated. But biologic materials have to break down. Over time, chance has to occur in cells, there has to be this gradual erosion of fitness in maternal cells. Why it arises? That's a big question why senescence has evolved. And that's a long standing problem. One of the and most of the research has been focused on as big multicellular organisms. So one of the Diaz in multicellular organisms is that once you've expressed most of your fitness early in life, you've had all your kids, you're beyond some point, you're not going to be having any more kids. Natural selection is not going to advance any trait that influence us late in life. And any kind of deleterious trait that only expresses itself late in life will be more or less immune to natural selection. So this just will naturally occur. Now, there can be grand parental effects, and some extreme cases of social organisms where you're expressing a little fitness, late in life through your kids, kids. But you know, most organisms aren't engaged in that kind of grand parental care. Another hypothesis is that there's, there's a trade off between genes that have have features and the phenotype that are really good in life, that are bad, late in life. And so since selections generally, you know, it's like a compound interest problem with a bank, you know, the faster you get your money in the bank, you make interest faster, and move on, and make interest off the interest. So the earlier get your progeny into the next generation, the better. Sometimes that might come with penalties for your fitness late in life. And so those are the two major hypotheses right now for the origin of aging or senescence and organisms. I
Nick Jikomes 1:01:44
want to see even a simpler question that I don't even really understand. So if we just think of a cell dividing, you've got your parent cell, you've got your daughter cell, the new cell will look fresher, it'll be rejuvenated, it won't have the broken stuff that the that the parent cell does. But how does? How does that partitioning even happen? How does the price how does the biology work such that one, one of the cells of this division gets all of the fresh stuff? And the other one does not? I don't I don't feel like I understand that? Well,
Michael Lynch 1:02:20
that's a big question for cell biology, and we don't really understand it fully either. I think it's not quite correct to think that all the good stuff goes into one. You know, most unicellular organisms are just reproducing by binary fission. And so there's gonna be a mix. And then it becomes very unclear, you know, whose parent and offspring? I mean, I guess the inclination would be to call the one who's got all the good, you know, more of the goodies than the other one would be the parent. But, you know, that's just sort of a semantic issue here. But we think at some, you know, things that reproduce by normal binary fission, just, you know, a split down the middle. It's not like budding yeast, where there's a distinction between mother and offspring cell. And then, you know, lots of good questions like, uh, you know, I've got a molecular machine like ATP synthase. Well, does the whole complex get inherited, intact from parent to offspring are their components come apart? And there are reassembled and mixture with new and old Arts at the same time? Those are difficult questions that people are still struggling with in cell biology, but they're at the heart of the problem, I think for cellular senescence.
Nick Jikomes 1:03:54
Another thing I want to ask you about is epigenetics. So if we go back even before Darwin, right, before Darwin, and Wallace, came up with the theory of natural selection, you know, people like famously Lamarck had his theory of acquired characteristics that, you know, you could obtain as an adult organism, some new trait during your life, and you could pass it on to your offspring. So that would be like, I don't know, lifting weights as an adult getting bigger muscles, and then your baby has bigger muscles, even though you weren't born that way you became that way during your life. It seems that recently in recent years, people are finding examples of the inheritance of acquired characteristics. So for example, I know that there's certain metabolic phenyl phenotypes that say a rodent can acquire as an adult, and then pass on to their children for some number of generations, the subsequent generations for you know, three or four generations at least, will have some metabolic phenotype that that their parent acquired during their lifetime. So it's not strictly encoded in the genes. It's some kind of epigenetic mechanism. Is how do you start to think about this? Are there true epigenetic inheritance mechanisms that don't depend on the actual DNA sequence? Is it truly possible for phenotypes to evolve within the lifetime of an organism and then persist in a population over time?
Michael Lynch 1:05:17
Yeah, that's a good question. I think there's a lot of misunderstanding about that. So I think we're all convinced now there, there are epigenetic mechanisms. So these are, you know, effects determined by the cellular environment that modifies various aspects of the genetic machinery, including the genome itself, but in non perfectly heritable ways, but they can influence what happens from generation to generation. That means that natural selection can take advantage of some epigenetic effects. So you could have two individuals, for example, with identical genomes, but one's been slightly modified by some kind of methylation or something that another one hasn't. And we'll have more success. But this is not likely to be a persistent evolutionary change. So the, the way, I like to think of it as an epigenetic effect as a transient mark, the DNA and that in some cases can be passed on to the next generation, but there's also a certain probability, it's going to be lost by chance, or just a race by natural cellular processes. The actual DNA doesn't change like that the only way the DNA is going to change lives by a real mutation at the nucleotide level. So you can have these epigenetic facts they can be transmitted, but then there's a bit of a loss each generation.
Nick Jikomes 1:07:00
So that sounds like they're probably inherently less stable, because they can be taken off and removed through normal cellular processes, like Yeah,
Michael Lynch 1:07:08
so you could have, you could have selection, persistently pushing you, in a certain direction, gain a little bit of loss, gain a little bit of slippage, and you will actually reach an equilibrium between the gains and the losses. And selection, if it was persistent, it could keep you over at this point, without any change at the DNA level. But then, if you stop selection in that directional way, you will just revert to where you were before, you'll go back to the prior equilibrium level of these epigenetic effects. So it can lead to a transient change for sure, but not a permanent change by itself.
Nick Jikomes 1:07:54
Oftentimes, when we think about natural selection, we think about a population boom, so there's sort of an excess of individuals produced, and then the population is called, because not all of them can be not all of them fit into the environment, the you know, the external environment can only has a certain carrying capacity, as an ecologist would say. There's also processes like that, that happen within organisms within cells. So for example, genes can duplicate. And then their functions can sort of deteriorate in complementary ways. And you can get some complexity evolving that way. Can you discuss that a little bit about, you know, within an individual within one genome, this process by which there's an expansion of stuff, a duplication of a gene, or a set of genes, or even a whole genome? And then there's sort of degenerative processes that where you can you can have a conservation of the overall function, but then you get a change in the architecture for how that that's actually happening?
Michael Lynch 1:08:49
Yeah, well, you mentioned ecology, I kind of like to think about, you know, gene duplication as a process that's similar to, you know, birth and death of individuals and a population. So, all genes and all organisms are subject to being duplicated. Now, they, you know, it's not always a complete clean duplication of the entire gene. But for purposes here, let's just think about it that way. So all genes are giving birth to baby genes that are direct copies of themselves. And we discovered quite a few years ago now that this occurs at a pretty high clip and all organisms. But then what happens to the duplicate if it's completely redundant, its event one of the copies is going to suffer from degenerative mutations and be lost and eventually become what was called a pseudo gene and maybe eventually be deleted from the genome. So there can be this steady state process and cell so in a population of individuals, if you keep the you know the age specific birth rate Some death rates constant, you will reach us what's called a stable age distribution. That stable age distribution actually can tell you something about the birth and the death rate. So a rapidly growing population will have lots of juveniles in it, and fewer adults. And demographers use that information to infer past history of birth and death. And we can do that with duplicate genes and genomes. So in bacteria, for example, I mentioned before, they're very streamlined genomes, they duplicate genes, pretty much the same rate that we eukaryotes do, but they have very few duplicate copies of genes in the genomes, probably because an additional copy is usually deleterious. And so the death rate for the access copies is relatively high. Whereas in US multicellular species, we have enormous numbers of duplicate genes in the genomes in all of our genomes, and many of them are very, very young. But many of them eventually make it to an old age, some, some get lucky in discover a new function. Sometimes they just partition up old function, so you had a ancestral gene with multiple functions. And you duplicate it, and now they partitioned up different functions, say in different cell types, and we call that sub functionalisation. So it's I like to think of this whole process is very similar to the way population ecologist think about the demography of individuals.
Nick Jikomes 1:11:42
And how do you start to think about things like the the speed of evolution in a given lineage, obviously, that's going to vary for an E. coli compared to a creature like us. But when you think about right, there's, there's a certain fundamental limit on the rate of mutations. There's this, you know, intrinsic error rate of the DNA replication machinery. There's, you know, how many mutagens are in the environment that the organism is exposed to. And then there's the population size effects that we talked about that dictate you know, how easily certain mutations can spread through the population? How do we start to think about the limits on how quickly adaptations can happen? How quickly the genome can change?
Michael Lynch 1:12:22
Yeah, well, that too, is a really good question. There's several ingredients here. One is, yeah, we needed to know something about the mutation rate. 30 years ago, we knew almost nothing about rates of mutations in different lineages. And today, we know a lot about it. And rates are per nucleotide per generation are, oh 100 to 1000 fold higher in eukaryotes than they are in bacteria. So that might seem good, but then you got to take into account the generation time, you know, bacteria might have a generation of only half an hour or an hour. Whereas some of us big multicellular organisms, it's more on the order of 1010 2030 years, and so on. So you got the element of time working. We have bigger genomes, on the other hand, so how does that all factor and there's more nucleotides that might contribute to adaptation. On the other hand, we just have smaller effective population sizes, a natural selection can't be as effective. So all these things work together to define the limiting rate of evolution. But we only have a crude idea how all this really works, because the reason is because we can kind of talk about this thing at the level of the nucleotide. But we don't yet have a good understanding of how nucleotide variation translates into phenotypic variation on which natural selection can operate. This is a really important question today in a changing world, because we'd like to know, you know, what is the limiting rate of environmental change? Beyond which organisms just cannot adapt?
Nick Jikomes 1:14:30
There's probably especially relevant humans
Michael Lynch 1:14:32
change. Maybe they're even keeping up at well, not keeping up. What we think goes on is, you know, in the perfect world, for an organism, say environmental changes changing on a gradient like this, what will happen when the organism will be chasing that environmental optimum, but there always be a lag because every time you move up, the environment moves up as well. So there'll be this lag and This ultimately leads to what we call a lag load, you are evolving in response to the changing environment. But as the lag load gets bigger, your population size is declining. And if your population size is declining, that means you're going extinct, you cannot keep up. So there's a critical rate of environmental change beyond which adaptation must not be possible must not be sustainable. And we don't have definitive answers on what that is and how that varies among phylogenetic lineages.
Nick Jikomes 1:15:36
Yeah, that's interesting, because, well, it's interesting as a human being, because, you know, I think you could make the case that our environment changes faster than any other organisms environment because of because of our cultural capabilities.
Michael Lynch 1:15:51
Yeah, but we modify our environment. And we live in ways I mean, that's what modern medicine is all about, right? We we live in ways that protect us not against just deleterious environments, but deleterious mutations. So the way I think of that is we're, you know, a lot of natural selection on humans as relaxed as a constant, just as a natural consequence, consequence of modern medicine. That's what modern medicine is all about, you know, living with our genetic afflictions.
Nick Jikomes 1:16:25
Yeah. So I mean, not only do we have a small population size, because we're big creatures, you know, relative to smaller creatures. But because humans, you know, because we have the brains we do, and we can invent things like we do. That's a further relaxation of selection, because we don't, you know, we're not subject to the same survival constraints that our ancestors were. How do you think that? I mean, are humans effectively? Are? Would you say that we're not evolving as quickly or not adapting as much that because selection is just such a weaker force for us? Like, how do you think about human evolution and the ways it might be sort of on a different trajectory than other creatures?
Michael Lynch 1:17:05
Well, there's a lot of interesting questions here that, you know, can be a bit of a landmine. But as I said, you know, modern medical procedures are all about, you know, allowing us to live with our genetic afflictions. There's no question about that. There's some other interesting aspects of just human biology. One, one way of thinking about this as the so called middle class neighborhood syndrome, you know, if the way natural selection operates is by variants and family size. And so an interesting question here is, how has that changed over evolutionary time? If everybody decided to just have two kids? Well, everybody's got the same fitness. Right? And that would be a different form of relaxation of up selection. I mean, there has to be, I'm not arguing that natural selection is not operating in some effective ways. On the human population. We're just indirectly by environmental change, you know, some of us are built better for certain environments than others. And as a whole population, this is probably having some effect. But evolution by natural selection to humans is very, very different than it is in other organisms for the mere fact that we're, we construct our own environments.
Nick Jikomes 1:18:38
Does that mean that just the, the level of influence of stochastic processes like genetic drift must be higher in our species than it would be for other species?
Michael Lynch 1:18:52
Yeah, I don't know that I would so much call it a issue with Tourette is just a relaxation of selection. In in some cases. Man, there's a lot a lot of other things to think about here. We're now one giant and mechanic population across the earth randomly mating across the years. So there, there are different segments of the human population in different environments exposed to different factors exposed to different, you know, privileges that we have with respect to medical procedures, and so on. So it's a it's a very heterogeneous sort of thing going on in the human population. And there's a lot of us today a lot more than there were historically the 10,000 that I talked about our historical effective size. That's not our effective population size today.
Nick Jikomes 1:19:49
See, it's larger today.
Michael Lynch 1:19:52
Yeah, I mean, just based on numbers alone, yeah.
Nick Jikomes 1:19:56
What are some of the things what do you what do you think are some The biggest misunderstandings that people, ordinary people or even biologists have about evolution, in terms of things that you feel like we have a good handle on and have a relatively solid understanding of that people are often mistaken or misled about in terms of how evolution actually happens.
Michael Lynch 1:20:19
Well, I think a big unfortunate aspect of biology is Darwin and some of his Bulldogs over the years who've written popular books espoused in the power of natural selection so much, that for most biologists, even many well trained biologist, even many people call themselves evolutionary biologists feel that everything is explainable by natural selection. And that just can't be true. But those are the avenues we have gone down as a consequence. There's lots and lots of excellent comparative biology being done in fields that you know, by people who don't normally think about evolution, but though they'll always be some teasing paragraph at the end of the paper explaining why these differences among organisms, what must have led to this divergence by natural selection. I mean, there's just, it's just accept that this has to be the process that bled to the diversification. And so there is no, it really diminishes the, you know, our ability to think about evolution, when we've already pre decided that the mechanism must be selection.
Nick Jikomes 1:21:47
What do you think are some of you know, in terms of the tree of life, and how it looks and how we understand it? And you know, even going back to where life came out, originated, in the beginning, what do you think are some of the major questions related to the origins of life and related to our understanding of evolution, the process of evolution, that you think will will probably start to answer in the next 510 15 years that we don't have a good handle on today?
Michael Lynch 1:22:19
Well, it's likely we'll, we'll have a bigger understanding of the tree of life itself. I think almost certainly, there's going to be a lot of interesting lineages, microbial lineages, in particular, to discover that might provide us with better insight into the order of events and the emergence of eukaryotes. The big problem with eukaryotes is, as I said, that there's many, many shared characteristics that we all as eukaryotes have, that must have been in the ancestor to us all, at least of the lineage we see today. The nuclear, you know, our DNA is inside a nucleus. We have mitochondria. And you know, the list goes on and on and on. The problem we have trying to understand the origin eukaryotes, is we don't have any ancestral lineages that have, you know, one or two of these changes that others don't have. So we can't, we have no way, really of convincingly come up with an order of events that lead to eukaryotes. This is why I'm wondering if someday we'll discover some what we might still call our keel lineages that have more eukaryotic like, features. So I would be extremely surprised if there aren't a lot of discoveries that will help us decipher the order of events towards what we call you carrier Genesis over the next few years.
Nick Jikomes 1:24:01
What are some of the questions that you're working on today that you're really excited about?
Michael Lynch 1:24:07
Well, as I said, we're interested in this broad connection between cell biology and evolutionary biology. And we have a lot of unsolved problems. Even even theory that hasn't met yet been developed to try and bridge this gap. We're not we don't really have a full grasp with how to link the power of cell biology and amazing level of observation with evolutionary theory, and this is going to have to involve much more complex theory than just saying trial, you know, there's two nucleotides at this one, one site in the genome. And let's figure out if you go this route or the other route, these are complex traits. But one of the things that we're most interested in is trying to understand how some complexities of the cell have evolved by semi neutral mechanisms. I'm trying to extend these ideas that I've mentioned earlier about the origin of genome complexity, the origins of cellular complexity, you know, one good example would be the ribosome. All organisms have ribosomes. But in eukaryotic lineages that we think have much smaller effective population sizes, there's many, many more proteins involved in the ribosome, than there are in bacteria. There's no evidence that our ribosomes are any better at translating, you know, more accurately, more rapidly. But somehow, we picked up this excess complexity over time. And you can talk about that with a number of different aspects of cell biology. So again, this raises the whole issue, not just at the genomic level, but now at the level of cellular complexity. That, you know, we went down certain kinds of evolutionary paths where there's certain kinds of population genetic environments that just predisposed us, us being the ancestral eukaryotes to go down this route of the path of emergence of cellular complexity. So that's, I think there's real possibility to broadening the field that way. And then the next step, a big step for me will be trying to link you know, the things that we've learned, we've learned that the genomic level now extending on the cellular level, and then bringing it up to the level of multicellularity. And how many aspects of the features of multicellular organisms are actually generated by semi neutral processes. And then put us in a, you know, a new kind of, you know, organismal real estate upon which natural selection copper. So, again, I think the key thing is separating out the what mechanisms lead to the origin of a certain change, and then natural selection, subsequent ability to move things around.
Nick Jikomes 1:27:31
Well, Professor Lynch, is there anything that you want to reiterate? Or any final thoughts you want to leave people with about evolution or about any of the topics that we covered today?
Michael Lynch 1:27:42
Well, I don't I don't think too much more. I guess my main point would simply be that, you know, there's a lot more to evolution than just natural selection. And if we really want to understand the mechanism evolution, we need to know how to put all these different themes together in a general cohesive framework.
Nick Jikomes 1:28:02
All right, well, Professor Michael Lynch, thank you for your time.
Michael Lynch 1:28:06
Thank you very much.
Evolution: Natural Selection, Genetic Drift, Origin of Life, Cellular Complexity, Epigenetics | Michael Lynch | #166