EEB 122. Principles of Evolution, Ecology and Behavior

Lecture 09.?The Evolution of Sex

https://oyc.yale.edu/ecology-and-evolutionary-biology/eeb-122/lecture-9

Sex is?a fundamental question in biology, because it shapes almost everything that we study in biology. Sex,?in terms of organized diploid Sex, has been around probably for about one and a half billion years, and it's had many consequences. We will look at some of the consequences of Sexual reproduction for large-scale patterns in the plant and animal kingdoms.?

Now I need to set this up by distinguishing between recombination, reproduction and gender, because the word?Sex?often elicits in the minds of non-biologists a composite of all three things.?

Recombination is the process that causes offspring to differ genetically from their parents and from each other. But there are always fascinating biological exceptions to the idea that recombination makes siblings different from each other. In some cases they are not, but normally they are.?

• For example, armadillos always have identical quadruplets, which makes them convenient for some things.

• Identical twins in humans, of course, are an exception, where the recombination has made them different from their parents, but they're still identical to each other, and that is because they derive from an early mitotic event in development; so they were originally the same zygote.

• And then we have the extravagance of polyembryonic wasps where a parasitic wasp lays a single egg into a caterpillar; the egg starts to develop into a blastula; the blastula fragments into hundreds or even thousands of pieces, each one of which then develops into an embryonic wasp.Some of those sister wasps differentiate into warrior castes and go cruising around the caterpillar, wiping out other wasps that may have laid their eggs into the caterpillar. They don't make it, they die, but they clear the way for the others, that then eat up the caterpillar and hatch as wasps, out of the caterpillar.?

Reproduction is not the same as recombination, and we can see comparatively, through these contrasting examples, why it is that recombination and reproduction are not always necessarily coupled. In us they are, but if we look at bacteria and clonal plants, we can see that they can reproduce without recombining.?

• Bacteria can actually arrange to have Sex and not divide at all. They can undergo a recombination event and simply change themselves genetically, and then wait for awhile and divide later.

• In plants, clonal plants have the option, many of them have the option of either producing aSexually or Sexually. Often they produce Sexually in the parts of them that will then disperse to another place, and aSexually in the parts of them that will stay here; here being more predictable than there.?

Gender is something that is really not at all the same as recombination or reproduction. Gender is maleness and femaleness. So it's all of the secondary Sexual characteristics of the two genders. And that is something that originated with the production of gametes of different sizes.?That didn't happen until after meiosis originated in evolution, and it then created a situation in which Sexual selection could occur; where there was one kind of selection on things that made lots of small gametes--sperm--and another kind of selection that operated on things that made a few large gametes--eggs.?

• Isogamy means that we're dealing with a species in which all of the gametes are the same size. That happens often in the protists, in unicellular algae and protozoa, that they produce gametes of the same size.?

• Anisogamy comes where there are gametes in two different sizes, the big ones being eggs and the small ones being sperm. So anisogamy is the condition with which most of you are familiar.?

• Syngamy means fusion of gametes to form a zygote; that is one step in the process of Sexual reproduction.?

• Karyogamy is fusion of the two gametic haploid nuclei. So the gametes come together, and then after that happens their nuclei fuse. And these things take time. We will see that?the time they take is some of the cost of Sex.

• Now mating types occur at this stage, with isogamous organisms, and they reduce inbreeding. Mating types are common in many unicellular algae and in many ciliates, like Paramecium. The population then differentiates and evolution produces a huge number of mating types.?

Now the traditional view on why Sex exists was formulated by August Weismann and then elaborated by Mueller, and clarified by Crow and Kimura.

• Recombination is there in nature basically because it increases the rate of evolution, and it does so in two ways.?It increases the rate at which two advantageous mutations can be brought together.?It increases the rate at which disadvantageous mutations can be discarded.?A consequence of this is that it decreases the probability of extinction.

• A, B and C are beneficial mutations that are arising at different places in the genome. They're not alleles with a single locus. They are three different genes whose combination it would be really cool to have, because it's going to improve reproductive success, defend you against diseases and so forth.

• In the aSexual population, first A pops up and it takes over the population because it's advantageous. Then C, which had occurred once before but not in combination with A, happens sequentially in the same organism that's already gotten A. So in the aSexual population the advantageous mutations have to happen one after another, in a descendant lineage, because there's no Sex to bring them together. AC dies out because shortly after it arose, AB came along and AB was preferential to AC, and then eventually C arises in an organism that already has A and B, and ABC takes over. That's a process of clonal interference.

• In the Sexual population these mutations can be conceived of as occurring at just about the same time as they did in the aSexual population, but they are rapidly brought together by Sex and recombination, and the combination ABC spreads through the population much earlier, achieving fixation here rather than here.?

Now if we look in small populations, the advantage of Sex is not nearly as great.?It still can be advantageous, but it's not as great as it is in the large population. Because there is less genetic variation in the small population.?You can think of the population size, all those genomes out there, as being a net that catches mutations. The smaller population is catching fewer of them, and therefore there are fewer things that it could bring together, and therefore it takes a longer time for Sex to become advantageous?in the small population,?because it has to wait for that mutation to come along. In the large population, it's relatively quickly.?

Now about the costs of Sex. In an isogamous organism the costs are genome dilution, the amount of time it takes to have Sex, and the risk of predation, of Sexually transmitted diseases and of the difficulty of finding mates.?

The cost of genome dilution basically is that by engaging in Sex you've made a decision that your offspring will only have 50% of your genes, and it's going to have 50% of somebody else's genes; whereas if you were aSexual it would be 100% your genes. And?this is indirectly also the cost of having males.?You don't really need to have males at all, if you're aSexual. We usually think of aSexual species as consisting only of females, and the reason for that is that they make eggs.

The other cost?is that if you have to go find a mate and take time to mate, you expose yourself to being eaten by a predator. In the process of mating, any kind of disease that mate has could jump into your body or into your offspring. It could be a selfish genetic element that got into your offspring, coming in through the genome of your mate. And it's pretty hard to find mates at low population density, which is why we find that aSexuality?increases in frequency as we go into the deep ocean. And if you look at the organisms that are specialized on eating the carcasses of dead whales, which drop onto the ocean floor infrequently and at great distances from each other, you discover that they have a higher rate of being aSexual, or being simultaneous hermaphrodites, than do things that say live on tropical reefs near the surface at high population density.?

Then if you have anisogamy, in its simplest form, the cost of males is a twofold cost. So if you're a female and you have the option of being aSexual,?basically if you count through to the number of grandchildren you have, you'll have twice as many grandchildren, if you don't make any males--if you only make daughters you'll get twice as many--through your female line, bringing--and this is because also the genome dilution effect is coming in.?So anisogamy, plus genome dilution, gives you a twofold cost of Sex.?

• Acarophenax is a mite that has an extreme example of local mate competition. Mites, many mites, not just Acarophenax, lay their eggs into their abdomen, where the eggs hatch out inside the mother, and the brothers then impregnate their sisters, inside the mother, and the brothers die and the sisters eat the mother. That's pretty spectacularly perverse.

• The question is?how many sons and daughters?should the mother?make?in order to get the maximum number of grandchildren??You only make one son with many daughters, and that's because that one son can make enough sperm to inseminate all of his sisters. And if you made two sons, you would have some sperm that was going to waste, and you could've used that egg to make another daughter that got inseminated.?

So the paradox of Sex is basically that's it regular, complicated and costly. And, as I indicated with the example of the yeast in the brewer's vat, aSex should rapidly take over Sexual populations. Nevertheless, when we look at the Tree of Life, we see that the majority of organisms are Sexual, and even the ones that we think of as being aSexual, like bacteria and viruses, in fact have evolved something like Sex.

• We've got this traditional explanation that Sex speeds up evolution and reduces extinction probability. But it has a problem. It is couched at the level of the species or the group.?And it's not strong enough to maintain Sex against the invasion of aSexual mutants. The reason is that if you think of it in terms of being good for the species because it causes the species to last a longer time before it goes extinct, well the generation times of species are orders of magnitude longer than the generation times of individuals.

• Vertebrate species last usually one to ten million years. Individuals last months to years. So about 106?difference in how fast things happen at the individual and the species level. So any individual advantage--for example, aSex--could be multiplied thousands or millions of times before the group or the species advantage of not going extinct so frequently could take effect.

• The individual advantage of aSex seems to be roughly twofold each generation, and that adds up to a big difference over a lot of generations. So aSexual mutants should always be taking over. But they don't.?

Now before I go into the solution to that problem, I want to give you a little bit of what we think is the evolutionary sequence in matters Sexual.?

• In prokaryotes, bacteria and archaea, probably the repair of ultraviolet damage to DNA was very important.

• Then mitosis originated and eukaryotic cell division. So once the eukaryote ancestor formed, with the proper cytoplasm and nucleus, and we had multiple chromosomes, mitosis originated. We're back about probably 1.5 to 2 billion years here.

• Then meiosis, which is really a very, very complicated symphonic arrangement, originated by a duplication and modification of mitosis.

• Then only after we had mitosis did we get isogamous mating types, and then we had the evolution of anisogamy. Now the evolution of anisogamy is actually a big deal because it is what eventually led to the differences between males and females.

• So Sexual selection only starts to happen after we have things that make gametes of different sizes.

The ideas about why gametes?of different sizes?happened are kind of interesting, because they're right at the origin of male/female difference.?

• One of the ideas is that a bigger egg would improve offspring survival. So some of the individuals in the population, in the isogamous population, might be under selection to produce bigger eggs, because they could then have babies that survive better. They could also produce more pheromones?so those eggs could advertise their presence better. A bigger egg is a better perfume factory.

• It is now frequency dependent selection. Once some of the organisms started to make bigger eggs, some of the others?could decide that they?don't need to make a big egg and invest a lot of energy in it because somebody else is doing that for me; instead they will?try to inseminate lots of eggs.?And they got selected to make sperm.?So they made many small gametes that could swim fast and were good at detecting perfume.

• Another idea on anisogamy is that those big eggs have got cytoplasmic organelles, and those cytoplasmic organelles have got their own independent genome in them, that they had when they came in as mitochondria or as chloroplasts or as spindle apparatus. And you don't want to generate a situation in which you have competing cytoplasmic genomes, because if you do, you get an uncontrollable evolution, microevolutionary process going on in the cytoplasm that can cause the takeover of the cytoplasm by a basically selfish mitochondrion or a selfish chloroplast.

• There are, in fact, mitochondrial cancers. There are cases in which mitochondria get out of hand and you end up with cells that are just packed wall to wall with mitochondria. You don't want that. You want to have the cell to be a relatively well regulated, well biochemically balanced environment. So one of the consequences of biparental inheritance, where you are only getting your organelles from one of the parents, normally the female, is that you avoid conflicts. This may or may not have been important at the origin of anisogamy, but it is certainly one of the reasons for its maintenance.?

We're dealing with a situation in which the original reasons are concealed by lots of layers of adaptations that have built up since then.?So we have to clearly distinguish between causes and consequences of Sex. But this is now very hard to do because the original causes are now covered up with so many of the secondary consequences. People have been repeatedly fooled by confusing consequences for causes.

Okay, so what kinds of forces maintain recombination??I'm only going to list the ones that I think remain plausible and can be demonstrated experimentally or comparatively. However, all the reasons that people have given for the origin and maintenance of Sex, that the list is on the order of forty or fifty hypotheses. The reasons as falling into two general categories: genetic and ecological.?

• There are two important genetic hypotheses. One is repair and the other is mutations, and in a sense mutations really are an issue of repair at the level of the population.

• There are ecological hypotheses. Parasites and pathogens, and the co-evolutionary problem that they pose, are accepted by many now as a major reason why Sex is maintained in populations.

• And it is also true that recombination spreads risks and hedges bets in ways that go beyond the issue of whether your children are going to be infected by a particular pathogen. You can deal with all sorts of ecological situations.?

In prokaryotes, a lot of repair mechanisms were evolved?and they are sophisticated. They're still in operation and?readily studied in microbiology laboratories. DNA polymerase itself does proofreading. If a nucleotide has been excised and is missing from the sequence, then you can use the complementary strand to patch it in. So that happens, and that needs a double-stranded DNA, not a single-stranded RNA. So if you're just dealing with a single-stranded RNA virus, it may very well have difficulty doing this kind of repair?and has a very high mutation rate. I want you to remember whenever I say mutation, that it is often a problem of inadequate repair. So the repair mechanisms actually control the mutation rates.?

In eukaryotes we have a lot more of?this kind of proofreading.?There are some repair mechanisms that actually need diploidy. So you have a whole extra chromosome. You have two double-stranded DNA molecules, and you can go to the alternate as a backup. So you can use that to repair any mutational damage.?

At the population level, the most interesting kind is recombinational repair, and that is because it isolates the defects on a subset of gametes. You can have mutations in five or six genes. Recombination could put them all into one set of gametes, and if those gametes die, those mutations are gone. So recombinational repair isolates and throws away, through natural selection, the defects in the genome.?

In a small population, the class of organisms that has the fewest mutations is eventually lost by drift. The first mutation arises, and eventually it drifts through the population and it is fixed. That will eventually happen. At that point all the organisms in the small population have one mutation.?Because they all have one, they can't get rid of it. The process happens again. So that leads to an inexorable increase in the number of mutations in the class of organisms that has the fewest.?And the kinds of organisms that are afflicted by this would be mitochondria and chloroplast in the germ line, and ancient aSexuals like bdelloid rotifers.?

What's going on basically is that this correlation between reproductive success and trait or genetic state gets wiped out by the Law of Small Numbers. As you decrease the size of the population,?natural selection becomes less and less powerful.?When it's very small, natural selection has very little opportunity to operate, and the reason it loses its force is that the correlation of trait variation with reproductive success is lost in the noise of a small number of arbitrary events.?

• So that's what's going to go on when you start off an oocyte with two or three mitochondria; that's a very small number of mitochondria to go into an oocyte, and that's a genetic bottleneck through which mitochondria will go in every generation. There might be 10,000 of them in your liver cells, but if they're a small number in oocytes, then they are going to experience drift.

• So you can think of this as stochasticity driving a wheel around, and there is a lever here that allows it to go forward but won't allow it to go back. Muller's ratchet will take this population and at first one of these genes will get replaced, through drift, by a deleterious mutation; then two and?so forth. The number of deleterious mutations that are carried by the least loaded genotype--that is, the type in the population that has the fewest deleterious mutations--it's increasing, and fitness is going down.

• This won't happen in a Sexual population or?an infinite aSexual population. The infinite aSexual population is big enough always to have some individuals in it that don't have any mutation, and they will keep taking over. But in a finite aSexual population, Muller's ratchet operates.?

So it's important in organelle DNA, and this problem of Muller's ratchet in organelle DNA could be solved, for example, if mitochondria had Sex.?In mammals, mutations in organelle DNA may be solved with gamete selection through oocytic atresia. One of the reasons why female mammals may make 7,000,000 oocytes, when they're embryos, and then kill most of them before they start menstruating, is that they are getting rid of mutations that may have built up in the mitochondria.?

What about the ancient aSexuals, those bdelloid rotifers? Well they have really two possibilities.?

• One is that they could try and arrange their physiology so that they could make the effects of any mutation more serious.?If you can make any mutation really serious, so that it kills anything that it occurs in, it has no chance to accumulate. It's only the deleterious but not fatal mutations that can accumulate. So that's a logical possibility, but biologically I find it implausible.

• Or they could always maintain a very large population, so that drift is not a problem. And most of the things that are ancient aSexuals do have at least large populations; not infinite but certainly large.

Nobody has ever seen a male bdelloid rotifer. Even though it's avoided the problems with mutations, we don't know how it's dealt with pathogens and parasites.?

Parasites are the principle way that the idea of co-evolution is realized in the context of the evolution of Sex.?

Red Queen in Lewis Carroll's book?Through the Looking Glass?says, "Alice, in this game you have to run as fast as you possibly can, only to stay in place."?So it's called the Red Queen Hypothesis, and the idea is that in evolution organisms are evolving as fast as they can, but they're in fact not increasing their fitness, and they are not decreasing their long-term extinction probability because the parasites and pathogens in their environment are coevolving with them and keeping up with them. They are?in a co-evolutionary arms race, then they may have to run as fast as possible?just to stay in the same place.?

What it requires is genetic variation for resistance in the host; genetic variation for virulence in the pathogen. We can see that in Daphnia and its parasites, and in crop plants and their pathogens. The parasites are selecting for host resistance. The hosts are selecting for parasite virulence, but the parasites have to keep hopping around, onto different hosts.?So that's just what you need to maintain Sex.

ASex hardly ever has an exactly twofold advantage.?There are cyclical parthenogens--Daphnia, aphids and?beetles, have a series of aSexual generations, followed by one Sexual generation.?You can have Sex about once every ten to a hundred generations, and it is almost as effective as having it every generation.?

And in mammals and birds, there are no costs of Sex,?because early development requires genes from each parent to activate in complementary fashion. So when you were a very, very small embryo, consisting of a few cells, you had to have some genes from your father turn on, and then some genes from your mother, and then some genes from your father, and then some genes from your mother, in sequential fashion, or development would not occur. That pretty much means that aSexuality becomes impossible.?And apparently there has been a process, an evolutionary arms race, probably involving conflict resolution, that has led to the kind of development that birds and mammals have.?

We now have so many advantages of Sex that we have a hard time explaining aSex. How did those bdelloid rotifers survive? We can easily understand why aSexuality would repeatedly originate and spread?like gangbusters. It has low cost short-term; big cost long-term. The long-term cost basically is pathogens and parasites, even if it can arrange a solution to the mutations that drive Muller's ratchet. If you look at the Tree of Life, the aSexual types are up on the twigs and they have Sexual ancestors.?

We have good individual selection explanations for recombination. You don't have to invoke group selection or species selection.?The ones that seem to be pretty general are repair -- mutations - and parasites. Those are certainly experimentally substantiated. We do not understand how ancient aSexuals have survived; that's an open issue. And Sex has had some very important macroevolutionary consequences.?Probably the most striking result?is the very existence of species.?What Sex does is it integrates populations and causes the co-adaptation of their genomes, so that we get breaks separating the things that we call species.?