3 Stories of Sex and Death in Evolution

Time and again, evolution has learned (after repeated blind alleys) to do what is best for the community in the long term and not always what is best for the individuals in the short term.  But such gains are fragile, easily lost if a cheater can gain a short-term advantage and its progeny take over the community.

Human societies have rules that encourage cooperation, and enforcement mechanisms for people who are reluctant to cooperate.  Cooperation in biology is very old, and it turns out that evolution thought about enforcement a billion years before Thomas Hobbes.  To see what this has to do with theories of aging, you’ll have to be patient.

Story #1: Conjugation and Cell Senescence
Story #2: Sex Required for Reproduction in Plants and Animals
Story #3: Antagonistic Pleiotropy — a Revisionist Theory


To begin, I’m going to ask you to think fresh thoughts about sex.  (Have I lost you already?)

Sex and reproduction, reproduction and sex.  Go together like a horse and carriage, right?  Well, how did it come to be that way? Sex is not a way to reproduce.  Sex is a way to share genes. But sex has become so tightly linked to reproduction that it requires mental gymnastics to imagine that it might have been otherwise.

Reproduction without sex—that’s not too hard.  It’s cloning. Or it’s mitosis, simple cell division which is how bacteria do it.

But sex without reproduction?  What’s that? Remember—sex is the mixing of genomes between different individuals with different genomes.  Does anyone do that except as a prelude to reproduction? What would it even look like?

Bacteria share genes willy-nilly.  They shed plasmids, which are little loops of DNA, and they pick up plasmids from around them.  The plasmid may be from the same kind of bacteria or another kind of bacteria entirely. Sometimes the gene they pick up is useful; sometimes, not so much;  sometimes the imported gene kills them. Bacteria can afford this daredevil lifestyle because there are a lot of them, and their credo is experimentation. Change or die.  Bacteria are constantly changing, not only because their generations are measured in hours instead of years, but the change from generation to generation is also greater than large animals and plants.  Under stress, they mutate and change even faster. Bacteria are artists of change, and their genius is figuring out what it takes to survive in the environment where they happen to be now. For bacteria, sex is spitting out plasmids and picking them up.

Bacterial plasmid (electron micrograph)

Story #1: Conjugation and Cell Senescence

Protists, or protoctista, are single-cell eukaryotes—far more complex and structured than bacteria, with a cell nucleus and many more organelles, a million times bigger than bacteria but still a single cell.  Examples are amoebas and paramecia. Protists share genes by a process called conjugation that challenges our idea of the individual.  As promised, sex in protists is not linked to reproduction…well, maybe indirectly linked, as we’ll see.


(This movie isn’t conjugation; it’s a hunting expedition.)

In conjugation, two paramecia (Dick and Jane) sidle up to each other and their cell membranes coalesce, forming one big cell.  Then the cell nuclei, where the chromosomes live, find each other and the two nuclear membranes open up and merge, just as the cells did.  A double size cell with double size nucleus, and two copies of each chromosome. Somehow the chromosomes pair up with the appropriate partner.  Like blind people trying to navigate a crowded room, how do the chromosomes arrange a meeting place with their partners? (If chromosomes had telephones, I suppose they would be cell phones.  OK, it isn’t funny.) Somehow, Dick’s chromosomes finds Jane’s corresponding chromosome, nearly identical but for the crucial variations that make them individuals. The chromosomes line up in pairs so they can swap genes with one another.  Genes cross over until each chromosome contains about half Dick’s genes and half Jane’s. Then—again using their cell phones for coordination—the chromosomes segregate. One from each pair goes north, the other goes south, so that when the nucleus splits in two again, each half has a full complement.  Two cells go their separate ways, but the cells that emerge from this process are no longer Dick and Jane. Each one of them is half Dick and half Jane, in its genes, in its cytoplasm, and in its mitochondria.

THIS is conjugation. It only takes place between protozoa of the same species.

Conjugation is sex without reproduction.  We started with two cells and ended with two cells.  They pooled their genes, but didn’t produce “offspring”.  Both Dick/Jane and Jane/Dick will someday undergo mitosis and copy themselves, but Dick and Jane have ceased to be, merged instead into an amalgam.

This has nothing
to do with
propagating

The species
is continued
as so many are
(among the smaller creatures)
by fission

(and this species
is very small
next in order to
the amoeba, the beginning one)

The paramecium
achieves, then,
immortality
by dividing

But when
the paramecium
desires renewal
strength another joy
this is what
the paramecium does:

The paramecium
lies down beside
another paramecium

Slowly inexplicably
the exchange
takes place
in which
some bits
of the nucleus of each
are exchanged

for some bits
of the nucleus
of the other

This is called
the conjugation of the paramecium.
poem by Muriel Rukeyser

Individual Selection and Group Selection,
Short-term Advantage and Long-term Welfare

Why do cells do this?  Let’s talk about fitness.  In the short term, the race is to the swift.  Reproduction is everything, especially among microbes which are always in a tight race with billions of others, and the one that reproduces fastest is the victor in Darwin’s lottery.  So natural selection at the individual level motivates Dick and Jane to get on with the business of copying themselves as fast aspossible.

Why did they take time out to merge their genes?  Dick and Jane individually must have thought they had a good thing going, each having survived a long while, and beaten out the competition.  They each had a combination of genes that work well together. Why would they take a flier on the off-chance that their genes might do even better in some other combination?  “Survival of the fittest” at its crudest level simply means that those who reproduce fastest crowd out everyone else.  Sharing genes takes time and energy. You can’t afford it.

To make this less abstract:  Imagine a puddle with cells swimming in it, all the same species.  Suppose some of the cells—the Joneses—go straight to work reproducing, doubling their numbers, while others—the Smiths—stop along the way to have sex with other Smiths.  They’re all increasing exponentially, but the Joneses grow at a faster rate. More doublings of the Joneses leads to a powerful numerical advantage. Pretty soon, the Joneses have overwhelmed the Smiths and crowded them out.  The Smiths are a thing of the past, driven to extinction. We say, “the Joneses have evolved to fixation.”

Short-term individual selection says “Don’t do it!  Don’t have sex!” But in the long run, the communal legacy is more robust if they DO share genes.  Having many diverse combinations of genes is insurance against changes in the environment, and a high-risk investment that just might yield big dividends if the right opportunity opens up in the future.  But there’s a danger that the Joneses will crowd out the Smiths in short order, and they won’t live to see the day when their robust diversity shows to their advantage.

After many, many cycles of losing sex in the short term and missing diversity in the long term, evolution stumbled on an expedient.  A counter was built into the chromosomes, counting replications. Everyone is allowed to clone about a hundred times, without sharing genes.  After that, without conjugation, the cell slows down and dies, stopped dead in its tracks. Every so often, every cell lineage must take time out for conjugation, or the lineage dies.

The counter is the telomere.  To enforce conjugation, nature arranged for telomerase to be locked away (in paramecia and other protists) during mitosis.  Each act of reproduction makes the telomeres a little shorter. Only during conjugation is telomerase unlocked, and the counter is reset, so the lineage can continue to clone.

Twenty years ago, William Clark wrote two books on this subject at a level accessible to readers of this column.  Sex and the Origins of Death, followed by A Means to an End.  I read both as they came out, and they had a profound effect on my thinking about evolution and aging.

Cell senescence is programmed death.  Can this be an evolutionary advantage?  Can programmed death evolve to protect the community from the fast crowd that doesn’t want to share their genes?  Sure, there is a long-term advantage, but how was evolution so clever as to arrange this? How did it happen that telomerase came to be sequestered, available only during conjugation?  I’ve looked through the evolutionary literature, and found no explanations, so I have asked this question myself, modeling with a computer simulation. The model works surprisingly well.  One important feature of the model is that there is a limited reservoir of the food that cells need in order to grow. This means that the “cheaters” who avoid conjugation and reproduce faster don’t have an advantage for long, because they use up the available food store faster.  Another crucial feature is that conjugation sometimes leads to combinations of genes that are more efficient at using food resources.

Here is a preliminary write-up — I plan to finish and publish this work in the near future.
 

Story #2: Sex and Reproduction in Plants and Animals

Half a billion years ago, there was an explosion of multicelled life.  Gene sharing is not so easily arranged when there are billions or trillions of cells in each fully-grown organism.  Sure, all life passes through an embryo stage, starting with a single cell. But embryos are hardly in a position to seek out a partner and share genes.  So evolution needed to invent anew both the mechanics of gene sharing and a means to enforce it on individuals whose primary Darwinian motivation was to reproduce as fast as possible.

So nature took the bull by the horns (or perhaps another part of his anatomy).  She laid down the law: “From now on, it takes two to tango. Anyone who wants to reproduce is going to have to share genes.”

Sex and reproduction were tied together anatomically, and the connection was so tight that no would-be cheater could get around the barriers.  For some (dioecious) species, there were two separate sexes so that no single individual had the tools to reproduce by itself.  In other (hermaphroditic) species, each individual could make both eggs and sperm, and there had to be barriers to self-fertilization, custom-designed for each anatomy.

Exactly how this came about is unknown.  Meiosis is an operation of baroque complexity, though clearly an outgrowth of both protist conjugation and mitosis.  Graham Bell (quoting Emerson) called it the Masterpiece of Nature, but neither he nor anyone proposed an evolutionary pathway that might have created it.

We know that this whole business of separate sexes and all the cellular and metabolic complexity that it entails managed to evolve, and we know that it offers no conventional advantage in terms that neo-Darwinist theory can understand.  No one doubts that the link between sex and reproduction femerged from a process of evolution, but the standard mechanisms recognized by conservative evolutionary theory are at a loss to explain it.

 

How do we understand evolution of sex?  What is the accepted explanation?

Classical evolutionary theory (neo-Darwinism) is in a bind.  The theory inherited from R. A. Fisher in the early part of the 20th Century insists that there is only one mechanism of evolution, and that is one-mutation-at-a-time.  Each incremental change has to provide a benefit that is capable of gradually spreading through the gene pool. In other words, all by itself and immediately it has to offer the bearers (on average) a faster rate of reproduction.   On the other hand, there are numerous examples of complex adaptations (like sexual reproduction) that provide no immediate benefit for reproduction, and that require many changes to many genes in order to be functional at all.  Classical evolutionary theory just says, “that’s a tough problem that we haven’t solved yet.”

But it’s more than that.  The very limited repertoire of mechanisms recognized by classical evolutionary theory quite obviously can never explain the provenance of sex, or of aging, or of countless other common traits.  Classical evolutionary theory is going to have to adapt or die.

I haven’t tried to model the evolution of sex because I can’t think how to do it.  The problem is just too hard—all the advantage is with the cheaters, who can reproduce twice as fast because they don’t have two different sexes to support.  Nevertheless, look around you—somehow nature managed to arrange most plants and animals in two sexes.

 

Story #3: Antagonistic Pleiotropy — a Revisionist Theory

Like sex, aging is a trait that benefits the community in the long run, but is costly to the individual in the short run.  It’s not as extreme as sex—the benefit is not so essential, and the cost is much less than the cost of sex. (Two sexes cuts fitness by half, by the classical definition of “fitness”.  Time and energy required for the mechanics of sex only add to the cost.)  So the problem is not as severe as Story #2, but once again, nature has a problem:  How to make death obligatory, so that there is population turnover and population diversity and (more important) so the population doesn’t explode past sustainable levels, leading to population crashes and extinction.

Nature’s solution was once again to tie together aging with reproduction, but the link isn’t nearly so tight and consistent as in the case of sex.  In fact, population can be kept within sustainable limits either by controlling fertility or limiting lifespan, or any combination of the two, so tying longer lifespan to lower fertility (and vice versa) helps to allow for diversity and flexible strategies, while guarding against those deadly population blooms.

The name for nature’s solution is Antagonistic Pleiotropy.  Fertility and longevity are coded in the genome in such a way that inheritance of lifespan and fertility are inversely linked.  Higher fertility goes with shorter lifespan. Lower fertility goes with longer lifespan. As long as the two vary together in this way, the threat of population explosion can be kept at bay.

You might be thinking: pleiotropy is everywhere.  We don’t need an explanation for pleiotropy, because it’s built into the way genomes are organized.  Very few genes have just one mission. A web of regulation affects everything at once, so that distinct traits emerges from many genes, and every gene contributes to many traits.  This is true of the way that adaptive traits are realized in nature. To think this way, you have to think of aging as an adaptive trait that nature actively wants to protect.

 

The Classical view of Antagonistic Pleiotropy

Contrast this with the orthodox theory of Antagonistic Pleiotropy, which has become the best-accepted theory for the evolution of aging.  In the orthodox theory, genes for fertility and other traits that are highly beneficial to the individual are tightly linked to deterioration that we call “aging”.  Out of the box, the genes work this way, and the forces of evolution have been unable, over half a billion years, to tease the two apart. There is a mighty motivation (says classical theory) to separate aging from fertility so that the individual can have the best of both worlds, but there are physical limitations or logical connections that make this impossible.  Hence, natural selection has had to swallow the bitter pill of aging in order to get the sweet nectar of faster reproduction.

In my version, antagonistic pleiotropy is an evolved linkage, after the fact.  In the standard version, antagonistic pleiotropy is an inescapable precondition, a given fact about the way genes work that evolution, with all her wiles, has been unable to evade.

How do we know that my interpretation of AP is the right one and all the theorists have it wrong?

  • Because the classic theory requires that every “aging gene” must have a benefit that more than compensates, and after 30 years of genetic experiments, pleiotropic costs.have been identified for only about half of the known aging genes.
  • We’ve seen that evolution is capable of some amazing feats.  It just doesn’t pass muster that evolution has been trying to find a pleiotropy bypass for half a billion years but doesn’t seem to be able to find one.
  • Because some of the best-known cases involve quasi-pleiotropic linkages that can be broken in the lab.  It’s just not that hard to have your cake and eat it, too. The first example was AGE-1, the first bona fide aging gene to be discovered (in lab worms, 1989).
  • When you look at the actual mechanisms of pleiotropy, many of them don’t seem to be functionally essential, but involve unexpected connections between unrelated functions.  The most recent example is that methylation aging seems to be inversely related to telomerase expression.

Of these 3 stories, the story of evolved Antagonistic Pleiotropy (#3) is the easiest to model and simulate, which is to say that the model requires few assumptions and works to evolve pleiotropy without a lot of adjustment or tinkering.  This alone gives me confidence that AP is evolved, and that the usual interpretation for the meaning of AP is upside down.

I have been working to turn my computer model into an academic article, and a draft of the paper, not yet submitted, is posted here.

25 thoughts on “3 Stories of Sex and Death in Evolution

  1. What about sex being an advantage (along with a shorter lifespan) because it enables faster evolution? After all sexual selection is much faster than random single mutations. This can be decisive in predator-prey relationships.

    It makes sense to me because short lived prey aways seem to get the advantage over their slower moving predators. It’s only the very young, old or sick that get caught and eaten. Jeff Bowles has written about this.

    • Yes – I think I’ve incorporated this in my story. In my opinion, the ability to adapt faster is a slow, group advantage. It is important in the long run, but easily lost to rapid individual selection if not protected.

  2. HI there ..if you are intersted in a simpler (I believe) and similar take on this line of thinking check out my article>>>

    https://jefftbowles.com/a-unifying-theory-of-the-evolution-of-sex-and-aging-via-predator-selection/

    in summary>>

    SEX EXISTS TO RAPIDLY CREATE BENEFICAL DIVERSITY IN GENES AND PHENOTYPES–

    Sex exists to rapidly increase beneficial phenotypic diversity in the face of evolving local predation-via recombination.

    The male sex exists to generate a high number of mutations that are usually detrimental, but occasionally beneficial with respect to surviving evolving predation – via the male mutation bias.

    Most male sex traits exist to attract predators who weed out the detrimental mutations and phenotypes, and select for the smaller number of beneficial mutations. Male traits are attractive to females but also attractive to predators – sexual selection.

    Some male sex traits exist to inform females that their male genes are older, predator-tested and superior to younger individuals’ genes (age markers).

    AGING EXISTS TO PREVENT THE LOSS OF BENEFICAL DIVERSITY IN GENES AND PHENOTYPES–

    Aging exists to prevent the loss of beneficial genetic diversity by restricting the amount of any one individual’s contribution to the gene pool.

    AND HERE WAS THE ABSTRACT>>>>

    Abstract: The last two major areas of evolution that continue to be shrouded in confusion and suffer from unsatisfactory explanation, are sex and aging. A new higher level order of selection is defined as a special form of species selection termed “predator selection” which allows for a simple solution to the question of the evolutionary purpose of sex and aging. Sex exists to generate and capture beneficial genetic and phenotypic diversity that helps a species survive when confronted with evolving predation. Aging exists to prevent the loss of this beneficial diversity. In the prolonged absence of predation, sex and aging will be lost in a species which will ultimately consist of all clonally reproducing females such as the all-female walking stick insect, whiptail lizards, Brahminy blind snakes, and cave crickets, to name a few. In the absence of predation, programmed aging will be lost and longevity will gradually evolve which can explain all species with exceptionally long lives based on their body size, such as arctic clams 500 years, mouse sized bats 41 years, humans 120 years, box tortoises 130 years, all cave animals, etc. These long-lived examples all have one thing in common: an excellent defense to predation, full body armor, isolation, flight, and extreme intelligence. This article basically summarizes the missing half of Darwin’s theory of evolution.

  3. A good example of this is the marbled crayfish, or Marmorkreb in German. They emerged from breeding in a German aquarium and have spread rapidly in the wild due to their ability to clone themselves.

    I wonder how long lasting their success will be, however? Once a predator appears that can catch them, or the crayfish themselves run out of food, they will have no genetic variability that could allow for some part of their population to survive, and they’ll all quickly disappear.

  4. I believe telomerase expression and epigenetic aging are not detached from each other.
    In the developing embryo and fetus a lot of telomerase must be expressed to keep stem cells able to divide, also a lot of epigenetic aging has to happen so that the development program counter keeps ticking.

    I have vague feeling that the time when aging and sex took their dominant form was the cambrian explosion when triploblastic animals with a complex structured body plan emerged. Such body is much harder to repair or to reproduce with budding, so these animals just took the path of reproduction by sex only and one way development with fast aging.
    Later where the niche allowed benefits for longer lifestyles the species evolved hacks to overcome the fast development and aging program. Crocodiles, naked mole rat, primates use different strategies for longevity.

    • >>In the developing embryo and fetus a lot of telomerase must be expressed…

      Actually, during development in the womb, human embryos lose 1/3 of their total telomere length in the first 9 months. This is as much as we lose in the ensuing 70 years.

      >>Such body is much harder to repair or to reproduce with budding, so these animals just took the path of reproduction by sex only and one way development with fast aging.

      In fact, there are simple animals (hydras) and, of course, many, many plants that reproduce by budding. Make no mistake about it. Creating the mechanics of sexual reproduction was a large, extensive project. And it yielded no benefit in “fitness” as neo-Darwinism defines fitness.

    • To take things right back to a basic question: do we actually have any evidence that epigenetic differentiation has any bearing on aging, other than the fact that ‘more’ differentiated cells have less access to telomerase?

      Is it not more likely that telomere length marks the ‘age’ of a cell (in terms of how many more times it can divide) and non telomeric epigenetic marks control the function of a cell – fibroplast, leukocyte, osteoblast, etc.?

      I am sure they are intimately connected, given that is how evolution builds things, but I think we badly need to draw a line somewhere to understand this properly.

      • There is the Ocampo Belmonte paper about epigenetic rejuvenation. There is no such result with telomer elongation as far as I know.
        Also it is a fact that during IPSC reprogramming epigenetic changes happen first, telomeres are elongated next.

        • Don’t forget Gabor that one of the OSKM factors, c-Myc, is right next to (and activates) TERT – so it could be argued that much of the benefit is coming from telomere elongation.

          Belmonte results (so far) are only with progeria-strains of mice, whereas Blasco has achieved impressive results with wild strains, using only HTERT – so I don’t think we can confidently say where the benefit is coming from.

          And given that the problems with OSKM-type regeneration are that if it is done for too long you are left with a lot of iPSCs in your body, we need to try and tease apart these factors and see what we need to do and what would be best avoided.

  5. Creatures that reproduce by cloning can have a great deal of diversity from splicing variations and splicing errors in genes that are divided into many segments. In some cases there are thousands of splicing variations for a single “gene”. This source of genetic diversity applies to non-clonal animals as well, and looks like an evolved mechanism of evolvability.

    • Genes do seem to have a great deal of flexibility, but obviously there are limits.

      The fact of the matter is that cloning is a niche way of reproducing and sexual sharing of genes is the norm. So clearly evolution favours the species that has diversity and can out adapt a cloned species.

      • Yet our energy factories are clonal. (Mitochondria do not share in sexual reproduction). I should say clonal with respect to the genes located within the mitochondria. Most of their genes have migrated to the nucleus and do share in sexual reproduction.

  6. “The changes that happen over 15 years in HGPS [progeria] also normally happen in dermal cells and vascular cells of normal individuals, but at a much slower rate. We all seem to have slow-acting HGPS.” James P. Watson @ Anti-Aging Firewalls. Splicing errors increase with age which looks like programmed aging to me. Splicing errors are reduced by
    Rapamycin
    Methylene Blue
    Sulforaphane

    • This is great stuff Robert, thanks for pointing it out.
      Alternative splicing as it relates to progeria certainly lends credence to the theory of programmed aging.
      Watson points out that there is a splicing factor, SRSF1 , which is induced by cellular senescence as well as cellular stress . This factor is also a cytoplasmic mTOR stimulator. So once again it’s rapamycin to the rescue.
      It’s also interesting that we all have a form of dermal progeria caused by alternative splicing which is secondary to UVA. MB has been shown to be very effective in skin rejuvenation.
      The problem with both rapamycin and MB is dosing. We’re really just guessing. And this is particularly true with MB.
      The best and most available form of sulforaphane continues to be chewed broccoli sprouts.

  7. Makes me think of the problem of gamblers ruin – that a player with limited wealth playing a fair game will eventually go bankrupt playing against an opponent with infinite wealth. Every morning a Hydra has a good chance of making it through the day but the environment is not static and eventually a black swan event will occur in the niche in which it lives. Sex and death make sense as a way of getting around gamblers ruin which would apply to long lived species and may be the reason why there aren’t too many of them around.

  8. Mark as promised an update on our pre-clinical trial to upregulate repair systems using natural activators: we have completed a 58 day study on rats. The treated old rat’s TNF-alpha and IL6 levels significantly reduced vs untreated old rats and reached at levels similar to young control rats. Similar results with barnes maze and grip strength.

      • Will reveal soon. Currently in process of filing patent. Post that will be submitting for publication in peer reviewed Journals. It was a cocktail of activators selected as per theory that the aging program through methylation changes selectively down regulates agonists of repair systems whereby the antagonists progressively dominate. I have shared the idea in my post mechanism of aging on my blog atomic bliss. I wanted to see what happens if we bring back the levels of agonists of the known major repair pathways – I tried to cover all – except direct upregulation of mitophagy as just could not source it so I can reveal it’s name as it could not be part of the study: urolithin a.
        As all the pathways seem to be interconnected I also wanted to see what happens if we resurrect some of the poles holding up a folding tent – will it be sufficient to raise the entire tent. Apparently it does. We did not expect such dramatic reversal. Also in some of the markers second month showed better results than first month so duration of treatment is also important. It’s like a 70 year old man getting back memory, strength and low grade inflammation levels of a 18 year old. Didn’t realize how expensive it could be – that too crossed our expectations.

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