Book notes - The Vital Question

It’s an amazing overview of what we have learnt about the origins of life on earth. The central piece of this story is “energy” — how energy and other constraints have played a key role in the rapid enhancement of some species (eukaryotes), while constraining the same in others (prokaryotes — bacteria and archaea).

The author raises a number of interesting questions and possibilities before dwelling into the details to answer the questions, and validate (or invalidate) various possibilities. One example of a typical question— did the nucleus of the eukaryotes appear first or was it the mitochondria that appeared first? The answer is — mitochondria appeared first and drove a lot of changes in the early eukaryotes. Nucleus is one of the many changes that happened in that short period of time. Other changes include sex, introns (non-coding regions of DNA) etc. Of course, the author does a much better job of maintaining the intrigue, and follows up with rigorous arguments to support the hypothesis.

The second part of the book places emphasis on how mitochondria and the requirements of having two genomes — mitochondrial and nuclear DNA — have played an important role in shaping the complex life around us. After a brief discussion on why mitochondria has to retain few coding genes (it has lost about 99% of the genes — most of them transferred to the nucleus — retaining just 13 of the coding genes), the main focus moves on to the coadaptation of mitochondrial and nuclear genomes. That’s because mutations continuously happen in both the parts. And these mutations need to work together to make the energy machinery in mitochondria work properly. Surprisingly, this coadaptation plays an important part in explaining many features and patterns of the complex life.

The most fascinating item in this book, for me, was how the energy/excretion constraints can influence or restrict the growth of the species. This is specially interesting when considered in the context of designing large distributed semi-autonomous AI systems that require vast amounts of data to be transferred between different computing nodes. I imagine we will run into the problem of similar constraints in such computing systems at some point in future. And if we do, my hope is that we can use some inspiration from the biological nano-machines to fundamentally overcome the issues of scale.

Some of the quotes, that I found interesting, are reproduced below almost exactly. (While those quotes may not make sense on their own, they are mostly noted down here to be able to recall important concepts quickly if you’ve already read the book.)

• “In the end, respiration and burning are equivalent; the slight delay in the middle is what we know as life” (page 65)
• “Six fundamental processes of living cells — carbon flux, energy flux, catalysis, DNA replication, compartmentalization and excretion” (page 129, page 96)
• Alkaline Hydrothermal vent (page 107)
• The last common ancestor of eukaryotes was a complex cell that already had straight chromosomes, a membrane-bound nucleus, mitochondria, various specialized ‘organelles’ and other membrane structures, a dynamic cytoskeleton, and traits like sex. (page 160)
• There could have been a single endosymbiosis at the origin of eukaryotes, and then almost no further exchange of genes between bacteria and eukaryotes; but plenty of lateral gene transfer over the entire period between various groups of bacteria. (page 164)
• The issue (of prokaryotic constraints) is energy availability per gene. (page 170)
• By our calculation, eukaryotes have up to 200,000 times more energy per gene than prokaryotes. (page 171)
• Scaling up a bacterium over orders of magnitude immediately runs into a problem with the surface-area-to-volume ratio. (page 173)
• This endlessly circular dynamic of gene loss and gain dominate bacterial populations. Over time, genome size stabilizes at the smallest feasible size, while individual cells have access to a much larger ‘metagenome’. A single E. coli cell may have 4,000 genes, but the metagenome is more like 18,000 genes. (page 181)
• The endlessly circular dynamic of gene loss and gain in free-living bacteria is replaced with a trajectory towards gene loss and genetic streamlining (in the endosymbionts that live inside another cell). Genes that are not needed will never be needed again. They can be lost for good. Genomes shrink. (page 181)
• We have retained just 13 protein-coding genes (in mitochondria). Assuming that the mitochondria derived from ancestors that were not dissimilar to modern α-proteobacteria, they must have started out with around 4,000 genes. Over evolutionary time, they lost more than 99% of their genome. (page 184)
• It’s striking that mitochondria have invariably retained the small subset of genes in all eukaryotes capable of respiration. On the few occasions that cells lost genes from the mitochondria altogether, they also lost the ability to respire. (page 188)
• In sum: sex arose very early in eukaryotic evolution, and only the evolution of sex in a small unstable population can explain why all eukaryotes share so many common traits. (page 199)
• That is the whole point of the nucleus: to keep ribosomes at bay. This explains why eukaryotes need a nucleus but prokaryotes don’t — prokaryotes don’t have an intron problem. (page 209)
• These two processes — accumulation of mildly damaging mutations, and loss of variation in selective sweeps — are together known as selective interference. Without recombination, selection on certain genes interferes with selection on others. (page 214)
• The last common ancestor of eukaryotes was already sexual, hence all her descendants were sexual too. While many microorganisms no longer have sex, very few ever lost sex altogether without falling to extinct. The costs of never having sex are therefore high. A similar argument should apply to the earliest eukaryotes. Those that never had sex — arguably all those that had not ‘invented’ sex — were likely to fall extinct. (page 215)
• While the lateral gene transfer could in principle avoid selective interference through recombination, Jez’s work suggests that this can only go so far. The larger the genome, the harder it becomes to pick up the ‘correct’ gene by lateral gene transfer. (page 217)
• One of the deepest distinctions between two sexes relates to the inheritance of mitochondria — one sex passes on its mitochondria, while the other sex does not. (page 220)
• For respiration to work properly, genes in the mitochondria and the nucleus need to cooperate with each other, and mutations in either genome can undermine physical fitness. (page 222)
• Mitochondrial variation alone can explain the evolution of multicellular organisms that have anisogamy (sperm and egg), uniparental inheritance, and a germline, in which female germ cells are sequestered early in development — which together form the basis for all sexual differences between males and females. (page 231)
• Consider mitochondria. The great respiratory proteins, which transfer electrons from food to oxygen while pumping protons across the mitochondrial membrane, are mosaics of numerous subunits. The largest, complex I, is composed of 45 separate proteins, each one made up of hundreds of amino acids linked together in a long chain. These complexes are often grouped into larger ensembles, ‘supercomplexes’, which funnel electrons to oxygen. Thousands of supercomplexes, each one an individual mosaic, adorn the majestic cathedral of the mitochondrion. (page 238)
• Sex is needed to maintain the function of individual genes in large genomes, whereas two sexes help maintain the quality of mitochondria. (page 241)
• The first few redox centres are iron-sulphur clusters. The iron is converted from Fe(3+) to Fe(2+) (or reduced) form, which can react directly with oxygen to form the negatively charged superoxide radical O2(-) with a single unpaired electron. (page 246)
• First, electron transfer slows down, and so the rate of ATP synthesis also falls. Second, the highly reduced iron-sulphur clusters react with oxygen to produce a burst of free radicals, resulting in the release of cytochrome c from its tethering to the membrane. And third, if nothing is done to compensate for these changes, the membrane potential collapses. This is the trigger for programmed cell death, or apoptosis. (page 247)
• Those (the cells) with the highest (energy) demands generally fail to meet them (the metabolic requirement) first. This is precisely the problem in mitochondrial diseases. Most involve neuromuscular degeneration, affecting the brain and skeletal muscle, essentially the tissues with the highest metabolic rate. (page 255)
• It’s a sobering thought that the requirement for two genomes in complex life could explain evolutionary conundrums as disparate as the origin of species, the development of sexes, and the vivid coloration of male birds. (page 261)