19 June 2017

Why would our genes kill us?

Evolutionary explanation

Yuri Deigin, Geektimes

In a post about aging and menopause as genetic mechanisms of population control, I mentioned that I consider aging as one of the varieties of the process of programmed phenoptosis (killing an individual). As expected, salmon surfaced in the discussion, and it surfaced belly up – the poor guy is sharply killed by the release of hormones almost immediately after spawning. For me, salmon is a symbol of the suicide program embedded in us, but there is nothing extraordinary about it – there are plenty of examples of active, sharp phenoptosis in nature.

The simplest and most well–known such examples are monocolor (or monocarpic) plants: wheat or corn, for example. Or flowers. Moreover, among them there are perennial species, and if some of them remove the flowers in time, these plants will not die, but will continue to live and even, perhaps, bloom again. At the same time, some trees have been living for millennia. This perfectly demonstrates that there are individuals with active phenoptosis, and there are individuals without it. Which means that biological systems don't have to age at all.

By the way, unicellular yeast, for example, also has active suicide. So, old yeast goes into apoptosis when resources begin to be scarce, and the population exceeds a certain limit. And if "hungry times" come, then up to 95% of the population can go into apoptosis, turning into food for the remaining 5%, which transform into spores and try to wait for better times to revive the colony.

There are also enough examples of programmed death among animals – in fish, insects, mammals. Here is a good, albeit incomplete overview of such species: Semelparous organisms reproduce only once in their lives and then die. The most well known ones are Pacific salmon.

The most illustrative example of a sharp phenoptosis among animals is the already mentioned Pacific salmon. Moreover, this is not a single species, like Atlantic salmon, but a whole genus Oncorhynchus, in which there are a dozen different species, most of which are semelparous (that is, they reproduce only once in a lifetime), although there are iteroparous like Atlantic salmon. That is, those that can reproduce several times, like most salmonids from the genus Salmo.

It has long been proven that salmon death should not be blamed on stress or exhaustion from rising against the current, but on the release of corticosteroids. Firstly, iterated salmon for some reason cope with stress very successfully, but they just like semelpari every spawning cycle go through all this whizzing with a rise against the current. Secondly, there are salmon species living in lakes without access to the sea, which thereby are spared the need to fight the current before spawning (that is, they have nowhere to take physical exhaustion), and they die after spawning anyway. Finally, even in artificial conditions, without any stress, semelparye salmon still die after breeding.

I don't say anything about insects at all – there are thousands of species that die immediately after they leave offspring: starting from the well-known May beetles or butterflies, and ending with my favorite cicadas, which can patiently live underground for 17 years in the larval stage, only to then hatch together and die in a few short weeks.

There are also examples among relatives closer to us. Male marsupial mice die after mating due to the same release of corticosteroids as salmon. A similar fate befalls mammals, the red-legged rat and the smoky mouse.

Therefore, it is naive to believe that an active suicide program cannot arise in the process of evolution. There are at least a dime a dozen such examples. Accordingly, a more gentle version of such a program called aging in no way contradicts the evolutionary theory, if only because there are empirical facts of the existence of even more drastic programs.

And, yes, the existence of programmed death in different species confirms the fact that evolutionary selection is carried out at different levels, and not only at the individual level. For many evolutionary biologists of the old school, this is heresy, since they grew up on the dogma "there can be no group selection!", but dogmas are worth absolutely nothing if they are refuted by facts. Therefore, today many biologists are inclined to the so–called multilevel selection - from genes to cells to individuals to groups:
And there is a lot of evidence confirming group selection. Starting from the very fact of the existence of multicellular organisms. After all, if cells had not learned, to the detriment of their personal interests, to put above the interests of their colony, which later received the title of "organism" – and a colony in which the vast majority of cells are doomed to death (since only sexual cells reproduce), then no multicellular cells would have appeared. And the altruism that yeast and social animals demonstrate, and even people who are ready to die for their children, relatives, friends and their people, would never have appeared without group selection.

By the way, sexual reproduction is also poorly explained without group selection. From the point of view of individual selection, it would be much easier and more profitable for any organism to share budding. But it is better for a pool of genes to mix with each other, creating more and more new combinations of replicators, thus increasing their chances of long-term survival and prosperity.

Exactly the same story with aging. It provides the gene pool of each population with insurance against extinction due to overpopulation. Moreover, some opponents of programmed aging agree with this point of view. However, then I don't really understand what they mean by programmed. For me, the fact that aging gives the population an evolutionary advantage suggests that evolution should have actively honed the mechanisms of both aging itself and its protection from hacking. And that is why we almost do not observe successful hackers of the aging program in nature – even if someone managed to stop aging and fix such a mutation in their offspring, their population would still die out due to a demographic catastrophe. Exceptions in the form of hydra or plants that can wait out the ice age for thousands of years only confirm the rule.

At the same time, the strangeness of the situation among gerontologists and population geneticists is that there are a minority of adherents of the hypothesis of programmed aging. A heated debate about the nature of aging raged in the middle of the 20th century, but then for some reason faded away. Moreover, they faded away not because this very nature of aging was unequivocally established, but because of the fact that he won groupthink is a phenomenon familiar to anyone who has read Anderesn's fairy tale "The New Dress of the King":

Groupthink is a psychological phenomenon that occurs in a group of people within which conformity or a desire for social harmony leads to incorrect or irrational decision–making. The members of the group try to minimize the conflict and reach a single solution without a sufficient critical assessment of alternative points of view, actively suppressing divergent opinions and isolating themselves from external influence

In such a situation, like-mindedness becomes more valuable than following logic and rational thinking. At the same time, the level of conformity increases significantly, information essential to the group's activities is subject to biased interpretation, unjustified optimism and belief in the unlimited possibilities of the group are cultivated. Information that does not agree with the accepted line is ignored or significantly distorted by the members of the group. As a result, there is an impression of unanimous decision-making. Groupthink can have far-reaching social and political consequences: there are many examples in history of tragic mistakes made as a result of such decisions.

So, the debate at the end of the 20th century came to naught because the neo-Darwinist camp, a priori denying group selection, took over in academic circles, forcing all its new adherents to swear that the king's dress is quite nice. And until the outsider Mitteldorf came to this festival of conformity in the 2000s and shouted that the king was naked, there were no new disputes about the nature of aging. But since then, the debate has resumed, and the debate is serious. Moreover, the multi-level selection paradigm, as I mentioned, is being accepted by an increasing number of scientists today.

The history of the academic confrontation between the two camps is perfectly described by the famous professor of ecology and evolutionary biology Michael Rosenzweig in his preface to Josh Mitteldorff's latest book "Aging – Adaptation as a result of group selection". Here's what he says, read it, I was not too lazy to translate:

If you say that natural selection changes Life for the benefit of species, almost any biologist specializing in evolution will protest: "No, no, no! Natural selection increases the fitness of individuals!".

Is there a difference? If individuals are improving, isn't the species also improving? Not always. Consider the individuals of predators. If predatory individuals improve to the maximum, they can completely exterminate all prey! What is good for an individual can destroy the whole group. And here a paradox arises.

Is it possible to avoid it? Can natural selection increase the chances that our predator will behave prudently? Or is he condemning him, like Samson, to perish under the arches of chrome, the columns of which he himself is trying to destroy?

How to force evolution to produce individuals who age, and how to force it to produce prudent predators, turn out to be closely related problems. Both increase the likelihood that a group of such individuals will survive. This may sound like a great idea, but generations of evolutionists have resisted all evidence that it exists because they couldn't come up with a mechanism that could counter the selfishness of natural selection. After all, "the effects of aging on an individual are completely detrimental, as it depletes its ability to survive and reproduce."

But, dear biologists, hold on to your hats! "The facts show that aging is selected not in spite of its fatal consequences for the individual, but because of them." Oh! This book will blow your brain. And the more you think you know everything about evolution, the bigger the fragmentation field will be.

In science, facts ultimately rule. And over the last quarter of a century, these facts have been accumulating. Mitteldorf considers them and treats them with respect. They range from computer modeling – which pits diligence against selfishness – to the genetics and biochemistry of aging. And the totality of these proofs loudly declares: "Aging is an adaptation. Aging is evolving."

But! If you have come here for evidence and arguments against evolution, then you are wasting your time. Mitteldorf does not argue with evolution or natural selection. By no means. On the contrary, it strengthens the evidence base in favor of one of the mechanisms of evolution – group selection. And thanks to this, evolutionists will be able to explain even more biological mysteries. And those riddles that confront even the smartest supporters of individual selection will fall under the blows of group selection. The first in a series of such riddles, by the way, is the riddle of the origin of sexual reproduction, and Mitteldorf gives a brief analysis of it.

Evolutionists have long known about the theory of group selection, and have long rejected it. Rejected due to the fact that individuals die faster than their groups die out. Therefore, they believed, any mutation that reduces the mortality of an individual would suppress any opposite gene that reduces the risk of extinction of the entire group. The case is closed! The mind, too.

And as if to aggravate the situation on purpose, the first work accepted for publication in favor of group selection (Lewontin & Dunn, 1960) modeled a system of semi-isolated families of mice and a somewhat strange family of alleles (genes) called tailless. Most male mice homozygous for this allele have zero evolutionary survival: either they die before birth, or they are simply infertile. Heterozygotes, although they reproduce, but the tailless allele they carry occurs in their offspring with a frequency of about 95% (instead of 50%). In other words, compared to wild types, tailless alleles have a competitive advantage in egg fertilization. Otherwise, the tailless ones would have been eliminated by natural selection.

Tailless alleles are highly selfish. Lewontin and Dunn showed that if the population of the muscular semi-isolate is small, then tailless alleles can destroy this entire population in one unlucky generation. With such a high rate of group extinction, group selection has a place to roam to demonstrate their strength. Tailless and wild type remain in the gene pool, because both group selection and individual selection have their influence.

I remember, as a graduate student, reading the above work by Lewontin & Dunn at a training seminar. It was presented as a special case; a case that is so difficult to achieve that it just demonstrates the improbability of group selection. Everyone agreed: we will be perfectly fine if we don't pay a single minute of attention to group selection anymore in our lives.

At about the same time, V. K. Wynne-Edwards published his massive collection devoted to the empirical facts of pronounced "diligence" in wild animals. He had no mechanism and no mathematics. Therefore, his work caused only our screams and vilification. We, the students, took an unspoken oath to ignore it.

In 1962, we faced the greatest challenge. Richard Levins published his seminal paper on fitness in heterogeneous environments (Amer Natur 96:361-373). We read and discussed his work, and everyone agreed: "Great job, yes, but his models are based on an unproven mechanism, namely group selection." We swept this inconvenient fact under the carpet and continued to admire the rest of the results of his work.

Once, at a meeting, I tried to directly challenge Levins' belief in group selection, but he remained steadfast. He was a Marxist even before he became a scientist. Thus, belief in group selection was an integral part of his thinking, because without group selection, Marxism would have failed. Since it was unthinkable for him, group selection had to be a reality.

I think you already have a good idea of the picture: two factions, one of the true supporters of group selection, who have never subjected it to scientific tests; and the other, all of us, who just as firmly believed that group selection should not be taken seriously.

And now, half a century later, at the age of seventy-five, I am suddenly writing a very laudatory preface to a book, the culmination of which is a demonstration that group selection is real. When I was twenty-five, I would rather have used such a book to build a fire. What happened?

And Josh Mitteldorf happened. And Greg Pollock, too. And a lot of biochemistry, which showed us the various intricacies of aging processes. At the same time, I am ready to admit that all the brilliant biochemistry in the world would not help me personally. Firstly, I am biochemically illiterate; I deliberately leave this field to others. But even if I understood biochemistry, it would not change my opinion: I would lump all biochemical achievements into one pile as submicroscopic empirical examples, and I would kick them into the already existing pile of examples from Wynn-Edwards. I needed an evolutionary mechanism, and even Richard Levins couldn't show it to me.

On March 20, 2000, when I was the editor-in-chief of the journal Evolutionary Ecology Research, I received the manuscript of the article. It was from Josh Mitteldorf, and this article was the beginning of my personal intellectual revolution. It discussed the phenomenon of increasing life expectancy caused by calorie restriction, which is an important topic that Josh fully addresses in the book. Then, on November 5, 2002, I took another blow that made my beliefs shake even more, namely, the manuscript of the article "Aging is evolutionarily selected for its own sake." Heresy, pure heresy!

Thank God, I always keep my scientific brain away from the editorial brain. As an evolutionist, I wanted to reject this manuscript, but as an editor, I saw its courage, and felt obliged to give it a chance to see the light. And for good reason. Mitteldorf worked on the missing part of group selection, its mechanism. It took me a year to get rid of my prejudices, and as a result, the article passed through an academic review and was published (Evol Ecol Res 6:937-953, 2004). Then followed a bold theory that finally cut off the way back: "Chaotic population dynamics and the evolution of aging" (Evol Ecol Res 8:561-574. 2006). It is this theory that makes up the main thesis of this book: "Aging and regulated death dates have evolved in order to stabilize ecosystems."

Let me summarize. Do you believe in population dynamics? Excellent. Then you should understand that aging is an adaptive consequence of "variation in population size that is not completely deterministic." After all, we do not know of any species with fully deterministic population sizes. Proven.

Now do you understand why I warned you that this book would blow your brain?

While the status quo of the impossibility of group selection was attacked on the one hand by Mitteldorf, on the other it was attacked by Gregory Pollock, whose manuscripts I received on June 11, 2003 (On suicidal punishment among Acromyrmex versicolor cofoundresses: Lack of self-interest, Evol Ecol Res 6:891-917 (2004) and 14:951-971 (2012)). And then the status quo was exposed in a silly light by theoretical simulations by Simon and Nielsen (Numerical solutions and animation of group selection dynamics (Evol Ecol Res 14:757-768 (2012)). My intransigence was replaced by acceptance, albeit with a negative emotional aftertaste, which very often accompanies situations when facts force a person to abandon a false belief.

What's the matter? Evolutionists are not invited to abandon their opinion that life expectancy is under the influence of selection. The evidence for this is huge. However, they are shown that they must abandon their belief that life expectancy is an adaptation that is under the influence of strictly individual selection. Instead, they should accept the probability that it is influenced by group selection. Unwillingly and unwittingly, in order to keep our species alive, we must self–destruct, following a program that leads us to death according to a schedule, no matter if you are a mouse or a human, a moth or a mollusk - the schedule may be different, but the end is the same, and it exists for the same reason, for the benefit of the species.

So it's time to throw off the blinders of group thinking, and admit that the king is naked, and aging is a program honed by group selection. And only when we know the enemy in person, we will be able to defeat him. Otherwise, pretending that it does not exist, we will continue to look for another stop-dead geroprotector that prolongs the life of mice by the same 20-30%, or starve in the hope of another 5-6 years of life.

By the way, we all know an excellent example of the fragility of the balance of power in multi-level selection. Periodically, the pressure of individual (quite individual, at the cellular level) selection in our cells overpowers the pressure of a higher level of hierarchy, and they decide to shake the old days and, remembering their unicellular past, raise a rebellion against the tyranny of the sexual line. Yes, yes, I'm talking about cancer. The fact that cancer is very genetically heterogeneous and that it occurs in almost all types of cells – from skin or brain to blood cells – suggests that it is based on a fundamental biological process. The cell wants to divide, and does not want to die.

And it can be understood. If it is still possible to cope with the desire to share, then it is very difficult to cope with the desire not to die. Because death sucks.

Portal "Eternal youth" http://vechnayamolodost.ru  19.06.2017

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