{"id":380,"date":"2015-05-26T15:43:26","date_gmt":"2015-05-26T15:43:26","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=380"},"modified":"2015-05-26T15:43:26","modified_gmt":"2015-05-26T15:43:26","slug":"vital-questions-part-3","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/05\/26\/vital-questions-part-3\/","title":{"rendered":"Vital Questions, Part 3"},"content":{"rendered":"

Week 3 – continued review of The Vital Question<\/a> by Nick Lane<\/p>\n

\"\"<\/p>\n

Nick Lane takes a look at the evolution of life on earth with an eye to explaining large-scale patterns, from a perspective based on the energy metabolism. \u00a0In the first week<\/a>, we talked about the origin of life and the structue of the cell. \u00a0In the second week<\/a>, we looked at the differences between eukaryotes and what came before, and asked about mergers of widely differing species. \u00a0In this third and final installment, I want to look at sex and death, and also to advocate for two important concepts that could broaden Lane\u2019s perspective yet further.<\/p>\n

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Sex<\/b><\/p>\n

Sex is the exchange of genetic material. \u00a0It was invented long before the first eukaryote. \u00a0Bacteria freely pass circular snippets of DNA called plasmids<\/a> among themselves, with little regard to where they came from or what they are for. \u00a0But in eukaryotes, sex became formalized, with exchange strictly limited to another of the same species (this is the definition of species), and it became compulsory, a prerequisite for reproduction in multi-celled species. \u00a0Many plants and some animals are hermaphrodites, with both male and female in one individual. \u00a0But most higher organisms have two separate sexes. \u00a0Lane proposes to explain all these patterns based on the most fundamental observation: \u00a0the mitochondria, having colonized the eukaryotic cell and brought with them their own DNA, have to remain healthy and work hormoniously with the host cell.<\/p>\n

bacteria enjoy the benefits of sex (fluid chromosomes) along with the speed and simplicity of cloning. But they don\u2019t fuse whole cells together, and they don\u2019t have two sexes, and so they avoid many of the disadvantages of sex. They would seem to have the best of both worlds. So why did sex arise from lateral gene transfer in the earliest eukaryotes?<\/p><\/blockquote>\n

This is an (uncharacteristic, for Lane) understatement. \u00a0For anyone who thinks in terms of the dominant paradigm of the 20th Century, evolution is all about individual competition and selfish genes. \u00a0Plasmids, as selfish genes, make perfect sense. \u00a0But the way that sex is implemented in eukaryotes makes no sense from the perspective of selfish gene theory. \u00a0The most successful members of the community have combinations of genes that work better than anyone else\u2019s. \u00a0What incentive do they have to share genes with their competitors, bringing their fitness down and their competitors\u2019 fitness up? \u00a0And the biggest violation of selfish-gene logic is the \u201ccost of males\u201d. \u00a0\u00a0Hermaphrodites have twice the fitness compared to diecious sex (2 separate sexes).<\/p>\n

The standard view is that this is a mystery, an isolated phenomenon that has yet to be reconciled with selfish gene theory. \u00a0I prefer to think that diecious sex is an unequivocal refutation of selfish gene theory, that evolutionary theory must expand to embrace a notion of fitness more sophisticated than \u201cevery gene for itself\u201d.<\/p>\n

 <\/p>\n

Origin of Sex<\/b><\/p>\n

Eukaryotes were around for half a billion years as single-celled protists. \u00a0Like bacteria and archaea before them, they were single cells, but the cells were 100,000 times larger and had a great deal of structure and mechanics that the prokaryotes didn\u2019t have.<\/p>\n

Lane says sex arose very early in the history of eukaryotes. \u00a0He cites as evidence (1) that the long list of traits that all eukaryotes have in common (but that prokaryotes lack) could only have arisen in an inbreeding population; and (2) even the simplest eukaryotes today (giardia<\/i> is the example that Lane cites) have the genes necessary for meiosis=cell mergers and gene exchange.<\/p>\n

Cloning may produce identical copies, but ironically this ultimately drives divergence between populations as mutations accumulate. In contrast, sex pools traits in a population, forever mixing and matching, opposing divergence. The fact that eukaryotes share the same traits suggests that they arose in an interbreeding sexual population. This in turn implies that their population was small enough to interbreed.<\/p><\/blockquote>\n

In a diverse population sharing genes, it is possible for different lineages to evolve different features, and then these features come together in a single offspring when they mated.<\/p>\n

An alternative hypothesis due to Margulis is that these diverse features were too different to have been encompassed in a single species (a single, interbreeding population). \u00a0Rather, the the different features that came together in eukaryotes evolved separately and then the separate species combined in rare cell-merger events, a process she wrote about as \u201cendosymbiosis\u201d, or acquiring genomes<\/a>.<\/p>\n

(How different are these two pictures, really? \u00a0We know that individuals with very different features must have shared genes; perhaps it is only a subtlety to ask whether these very different individuals were part of one wide-ranging inter-breding population, or of separate demes that might be called different species.)<\/p>\n

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Sex and Reproduction were Different Functions<\/b><\/p>\n

In the one-celled eukaryotes, sex and reproduction were separate and unrelated functions. \u00a0Reproduction occurred by mitosis, simple cell division, producing two clones. \u00a0Sex occurs via conjugation, in which two individuals merge their cells, and merge the cell nuclei temporarily. \u00a0Their chromosomes mix, and as each chromosome finds its opposite number, genes can cross over between the two chromosomes. \u00a0When the merged cell comes apart, the two individuals that go their separate ways are no longer the same two individuals that came together an hour earlier. \u00a0Instead, there are two new individuals, each a hybrid.<\/p>\n

 <\/p>\n

Could mitochondria have \u201cagitated for sex\u201d?<\/b><\/p>\n

Lane sees the cellular invasion by mitochondria as the source of everything eukaryotic. \u00a0Sex, as we have seen, is a particularly thorny problem\u2014not just the mechanics, but the fact that (short-term) selective pressures should have been acting against<\/i><\/b> it. \u00a0But while sex would not be adaptive for the host cells (in the short run), it would have provided the only effective way for the mitochondrial \u201cinfection\u201d to spread. \u00a0There must have been a long transition period in which the mitochondria were not fully domesticated, and had their own ideas about what it means to be \u201cadaptive\u201d. \u00a0After mitochondria learned to be endosymbionts, they would have trouble surviving outside the host cell, and trouble penetrating the cell walls of other cells, in order to spread from one host to another. \u00a0So perhaps it was the genius of the mitochondria to induce some chemical change that would soften the host\u2019s cell wall, and to promote behaviors that would seek other cells to merge with, giving the mitochondria a chance to spread.<\/p>\n

My take: this hypothesis has the virtue of being \u201cconservative\u201d in the sense that it fits well within the predominant selfish gene paradigm. \u00a0What could be more selfish than for the mitochondria to want to spread themselves? \u00a0But at a slightly deeper level, the main thing that the selfish gene paradigm has going for it is that it is supposed to provide an explicit mechanism for natural selection, i.e., that the gene that makes the most copies of itself is the one that prevails. \u00a0In this case, Lane\u2019s hypothesis suffers for want of a mechanism how the mitochondria were able to take control of the cell\u2019s behavior and override the interest of the genes in the nucleus for which sex was a liability.<\/p>\n

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Difference between plants and animals<\/b><\/p>\n

Mitochondria reproduce within a cell so their DNA is copied many times for each one time that the nuclear DNA is copied. \u00a0Furthermore, mitochondria exist in an environment of high-energy chemistry (ROS) that is a constant threat to the integrity of their DNA. \u00a0So we expect high mutation rates in mitochondria, perhaps high enough to cause permanent damage and impaired performance. \u00a0Somehow, in domesticating its mitochondrial guests, cells had to learn to culture the healthy ones and eliminate the damaged ones. \u00a0Otherwise, mitochondria would gradually mutate and degrade over time.<\/p>\n

This is a genuine conundrum, about which there are really no cogent ideas in the literature. \u00a0If natural selection keeps populations healthy (and even improves them gradually) by filtering out the dysfunctional, where is the selection on mitochondria as they reproduce within a cell? \u00a0Most dangerous of all would be the possibility of Darwinian competition within a cell among the different mitochondria. \u00a0Some mitochondria might devote less of their metabolisms to serving the host cell and more to reproducing faster than their sisters. \u00a0This could produce an evolutionary advantage within the cell for the slackers, the least useful mitochondria. \u00a0Selfish evolution of mitochondria is an existential threat to the partnership between mitochondria and host.<\/p>\n

Lane devotes a whole chapter to speculation about the resolution of this problem. \u00a0We know that nature has managed to keep mitochondria healthy over billions of generations, in all surviving eukaryotes, but we weren\u2019t around to watch how the mitochondria were tamed or convinced to submit to the hegemony of the cell nucleus. \u00a0What we have to go on are surviving patterns that may bear the imprint of this ancient battle. \u00a0The fact that mitochondria are inherited through the female line only is one piece of data. \u00a0A difference in strategy between plants and animals may be another legacy of the battle: any cell of a plant\u2019s meristem<\/a> can grow into a seed that grows to a new plant, but in animals, the \u201cgerm line is segregated\u201d, meaning that there is specialized reproductive tissue, protected from the earliest stage of embryonic development. \u00a0Lane relates this difference to the fact that animals have a higher metabolic rate, with more mitochondria that are more active, thus a lower mitochondrial mutation rate. \u00a0There may even be a connection to the reason that females lose their fertility earlier than men; the mitochondria become more highly mutated late in life, and it would be a risk to the offspring to launch them into life with a stock of mutated mitochondria. \u00a0Males can afford to reproduce later in life because they don\u2019t contribute mitochondria to the offspring.<\/p>\n

 <\/p>\n

Aging and death<\/b><\/p>\n

Lane doesn\u2019t have a lot to say about aging in this volume, but he does note that aging only really became an option once the germ line was segregated. \u00a0Germ line cells need to have full capacity for regenerating everything (pluripotency<\/a>) but cells of the soma have the luxury of specializing, and one option is to differentiate and grow once and for all, creating an organ that must last a lifetime (like a brain or heart).<\/p>\n

In the end, Lane\u2019s explanation of aging lands at a place very close to conventional theories based on tradeoffs<\/a>. \u00a0The somatic tissues of the body can\u2019t be simultaneously good at everything, and they are specialized to their differentiated purpose, to the detriment of the ability of regenerate. \u00a0Hence they are prone to wear out over a lifetime. \u00a0I find this explanation less compelling than many of his other ventures, but this is probably inevitable, since evolution of aging is the area where my own thoughts are most highly developed.<\/p>\n

Lane goes on to describe his own version of the mitochondrial free radical theory of aging, which is not an evolutionary theory. \u00a0He elaborates why, despite the many well-known failures of this theory in its naive form, he nevertheless finds a core of truth in it.<\/p>\n

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Conjugation of Ciliates<\/figcaption><\/figure>\n

Sex and Death in Protists Presages Sex and Death in Multicelled Plants and Animals<\/b><\/p>\n

The mechanics of conjugation in protists looks strikingly like the mechanics of sex in later multi-celled organisms. \u00a0The way in which the cells merge, the crossover of chromosomes, the particular genes that are involved all point to a close relationship. \u00a0Most striking is the strange mechanism of doubling the chromosome population before dividing it in half, and then in half again. \u00a0The very arbitrariness of this behavior, and the fact that we see it both in protist conjugation and in male-female sex, is attests to the fact that latter evolved from the former.<\/p>\n

I\u2019ve said that sex and reproduction in one-celled eukaryotes are separate, unrelated functions. \u00a0But there does exist one connection in ciliates<\/a>, an advanced group of protists including the paramecium. \u00a0Telomeres get shorter and shorter with each cell division. \u00a0This is cellular senescence. \u00a0It is permitted to continue, threatening the cell\u2019s viability, because telomerase is repressed, and only comes out to restore the telomere when two individuals conjugate.\"\"<\/p>\n

Thus, already in the early ciliates, cellular senescence has the purpose of enforcing conjugation. \u00a0This ancient form of aging evolved to protect population diversity. \u00a0And in higher organisms to this day, cellular senescence contributes to the death of the individual, assuring that the population continues to be enriched by new combinations of genes. \u00a0The rationing of telomerase in protists presages the rationing of telomerase in you and me.<\/p>\n

(William Clark tells this story in his very readable book, A Means to an End<\/a>. \u00a0My current project is a computer model demonstrating how telomerase rationing evolved on this basis.)<\/p>\n

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Where to go from here? \u00a0Two suggestions<\/b><\/p>\n

I am an enthusiastic supporter of Lane\u2019s program, trying to understand the broad outlines of evolution, and why life is the way it is. \u00a0I offer, from my own experience, two more themes that might complement his program.<\/p>\n