Evolution of the Larynx

Primates already had bigger and more diverse larynxes, before humans came on the scene.

While oxygen was originally a photosynthetic waste product and toxic to all life forms, we gradually got used to it. Some, especially the eukaryotes, made a virtue of oxygen's great electronegativity to adopt a new and more efficient metabolism with oxygen as the final electron acceptor. This allowed the evolution of large animals, which breathe oxygen. All this happened in the oceans. But it turns out that it is far easier to get oxygen from air than from water, leading air breathing to evolve independently dozens of times among fishes of all sorts of lineages. Lungs developed from many tissues, but rarely from the swim bladder, which had critical roles revolving around constant and controllable pressure, pretty much the opposite of what one needs in a lung. So in our lineage, the lung developed as an adjunct to the digestive system, where the fish could gulp air when gill breathing didn't cut it. 

Overview of the atmosphere of earth. Lungs were only possible when the level of oxygen in air rose sufficiently, and respiration of any kind only when oxygen had vanquished the originally reducing chemical environment.

This in turn naturally led to the need to keep food from going into the nascent lung, (air going into the stomach is less of a problem.. we still do that part), thus the primitive larynx, which just a bit of muscle constricting the passage to the lung. As this breathing system became more important, regulating access to the lung became more important as well, and the larynx developed more muscles to open as well as close the air passage, then a progessively more stable and complex surrounding structure made of cartilage to anchor all these muscles. 

But that was not the end of the story, since animals decided that they wanted to express themselves. Birds developed an entirely different organ, the syrinx, separate from the larynx and positioned at the first tracheal branch, which allows them to sing with great power and sometimes two different notes at once. But mammals developed vocal cords right in the center of the larynx, making use of the cartilaginous structure and the passing air to send one fluttering note out to the world. The tension with which these cords are held, the air velocity going past them, and the shapes used in the upper amplifying structures of the throat, mouth, and sinuses all affect the final sound, giving mammals their expressive range, such as it is.

So why are humans the only animals to fully develop these capacities, into music and speech? Virtually all other mammals have communicative abilities, often quite rich, like purrs, barks, squealing, mewling, rasping, and the like. But none of this approaches the facility we have evolved. A lot can be laid to the evolution of our brains and cognitive capacities, but some involves evolution of the larynx itself. A recent paper discussed its trajectory in the primate lineages.

Comparison of representative larynxes, showing a typical size difference.

The authors accumulate a large database of larynx anatomy and function- sizes, frequency patterns, evolutionary divergence times- and use this to show that on average, the primate lineage has larger larynxes than other mammals, and has experienced faster larynx evolution, to a larger spread of sizes and functions, than other mammals. The largest larynxes of all belong to black howler monkeys, who are notorious for their loudness. "The call can be heard up to 5 km away." They also claim that among primates, larynx size is less closely related to body size than it is among other mammals, suggesting again that there has been more direct selection for larynx characteristics in this lineage.

Primates (blue) show greater larynx size and variability than other carnivores.

This all indicates that in the runup to human evolution, there had already been a lot of evolutionary development of the larynx among primates, probably due to their social complexity and tendency to live in dense forested areas where communication is difficult by other means. Yet do primates have vocal languages, in any respect? No- their vocalizations are hardly more complex than those of birds. Their increased evolutionary flexibility at most laid the physical groundwork for the rapid development of human speech, which included a permanently descended larynx and more importantly, cognitive and motor changes to enable fine voluntary control in line with a more powerful conceptual apparatus.

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Stem Cell Asymmetry Originates at the Centrosome

At least sometimes.. how replication of the centrosome creates asymmetry of cell division as a whole, and what makes that asymmetry happen.

Cell fates can hinge on very simple distinctions. The orientation of dividing cells in a tight compartment may force one out of the cozy home, and into a different environment, which induces differentiation. Stem cells, those notorious objects of awe and research, are progenitor cells that stay undifferentiated themselves, but divide to produce progeny that differentiate into one, or many, different cell types. At the root of this capacity of stem cells is some kind of asymmetric cell division, whether enforced physically by an environmental micro-niche, or internally by molecular means. And a dominant way for cells to have intrinsic asymmetry is for their spindle apparatus to lead the way. Our previous overview of the centrosome (or spindle pole body) described its physical structure and ability to organize the microtubules of the cell, particularly during cell division. A recent paper discussed how the centrosome itself divides and originates a basic asymmetry of all eukaryotic cells.

The centrosome is a complicated structure that replicates in tandem with the rest of the cell cycle. Centrosomes do not divide in the middle or by fission. Rather, the daughter develops off to the side of the mother. Centrosomes are embedded in the nuclear envelope, and the mother develops a short extension, called a bridge or half-bridge, off its side, off of which the daughter develops, also anchored in the nuclear envelope. Though there are hundreds of associated proteins, the key components in this story are NUD1, which forms part of the core of the centrosome, and SPC72, which binds to NUD1 and also binds to the microtubules (made of the protein tubulin) which it is the job of the centrosome to organize. In yeast cells, which divide into very distinct mother and daughter (bud) cells, the mother centrosome (called the spindle pole body) leads the way into division and always goes into the daughter cell, while the daughter centrosome stays in the mother cell.

The deduced structure of some members of the centrosome/spindle pole in yeast cells. Everything below the nuclear envelope is inside the nucleus, while everything above is in the cytoplasm. The proteins most significant in this study are gamma tubulin (yTC), Spc72, and Nud1. OP stands for outer plaque, CP central plaque, IP inner plaque, as these structures look like separate dense layers in electron microscopy. To the right side of the central plaque is a dark bit called the half-bridge, on the other side of which the daughter centrosome develops, during cell division.

The authors asked why this difference exists- why do mother centrosomes act first to go to the outside of the cell where the bud forms? Is it simply a matter of immaturity, that the daughter centrosome is not complete at this point, (and if so, why), or is there more specific regulation involved that enforces this behavior? They use a combined approach in yeast cells combining advanced fluorescence microscopy with genetics to find the connection between the cell cycle and the progressive development of the daughter centrosome.

Yeast cells with three mutant centrosome proteins, each engineered as fusions to fluorescent proteins of different color, were used to show the relative positions of KAR1, (green), which lies in the half-bridge between the mother and daughter centrosomes. Three successive cell cycle states are shown. Spc42, (blue), at the core of the centrosome, and gamma tubulin (red; Tub4, or alternately Spc72, which lies just inside Tup4), which is at the outside and mediates between the centrosome and the tubulin-containing microtubules. Note that the addition of gamma tubulin is a late event, after Spc42 appears in the daughter. The bottom series is oriented essentially upside down vs the top two series.

What they find, looking at cells going through all stages of cell division, is that the assembly of the daughter centrosome is  stepwise, with inner components added before outer ones. Particularly, the final structural elements of Spc72 and gamma tubulin wait till the start of anaphase, when the cells are just about to divide, to be added to the daughter centrosome. The authors then bring in key cell cycle mutants to show that the central controller of the cell cycle, cyclin-dependent kinase CDK, is what is causing the hold-up. This kinase (a protein that phosphorylates other proteins, as a means of regulation) orchestrates much of the yeast cell cycle, as it does in all eukaryotic cells, subject to a blizzard of other regulatory influences. They observed that special inducible mutations (sensitive versions of the protein that shut off at elevated temperature) of CDK would stop this spindle assembly process, suggesting that some component was being phosphorylated by CDK at the key time of the cell cycle. Then, after systematically mutating possible CDK target phosphorylation sites on likely proteins of the centrosome, they came up with Nud1 as the probable target of CDK control. This makes complete sense, since Spc72 assembles on top of Nud1 in the structure, as diagrammed at top. They go on to show the direct phosphorylation of Nud1 by CDK, as well as direct binding between Nud1 and Spc72.

Final model from the article shows how the mechanics they revealed relate to the cell cycle. A daughter centrosome slowly develops off the side of the mother centrosome, but its "licensing" by CDK to nucleate microtubules (black rods anchored by the blue cones) only comes later on in M phase, just as the final steps of division need to take place. This gives the mother centrosome the jump, allowing it to migrate to the bud (daughter cell) and nucleate the microtubules needed to drive half of the replicated DNA/chromosomes into the bud. GammaTC is nucleating gamma tubulin, "P" stands for activating phosphorylation sites on Nud1.

This is a nice example of the power of a model system like yeast, whose rich set of mutants, ease of genetic and physical manipulation, complete genome sequence and associated bioinformatics, and many other technologies make it a gold mine of basic research. The only hard part was the microscopy, since yeast cells are substantially smaller than human cells, making that part of the study a tour de force.

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Are Attention and Consciousness the Same?

Not really, though what consciousness is in physical terms remains obscure.

A little like fusion power, the quest for a physical explanation of consciousness has been frustratingly unrewarding. The definition of consciousness is fraught to start with, and since it is by all reasonable hypotheses a chemical process well-hidden in the murky, messy, and mysterious processes of the brain, it is also maddeningly fraught in every technical sense. A couple of recent papers provide some views of just how far away the prospect of a solution is, based on analyses of the visual system, one in humans, the other in monkeys.

Vision provides both the most vivid form of consciousness, and a particularly well-analyzed system of neural processing, from retinal input through lower level computation at the back of the brain and onwards through two visual "streams" of processing to conscious perception (the ventral stream in the inferior temporal lobe) and action-oriented processing (in the posterior parietal lobe). It is at the top of this hierarchy that things get a bit vague. Consciousness has not yet been isolated, and how it could be remains unclear. Is attention the same as consciousness, or different? How can related activities like unconscious high-level vision processing, conscious reporting, pressing buttons, etc. be separated from pure consciousness? They all happen in the brain, after all. Or do those activities compose consciousness?

A few landmarks in the streams of visual processing.  V1 is the first level of visual processing, after pre-processing by the retina and lateral geniculate nucleus. Processing then divides into the two streams ending up in the inferotemporal lobe, where consciousness and memory seem to be fed, while the dorsal stream to the inferior parietal lobule and nearby areas feed action guidance in the vicinity of the motor cortex. 

In the first paper, the authors jammed a matrix of electrodes into the brains of macaques, near the "face cells" of the inferotemporal cortex of the ventral stream. The macaques were presented with a classic binocular rivalry test, with a face shown to one eye, and something else shown to the other eye. Nothing was changed on the screen, nor the head orientation of the macaque, but their conscious perception alternated (as would ours) between one image and the other. It is thought to be a clever way to isolate perceptual distinctions from lower level visual processing, which stay largely constant- each eye processes each scene fully, before higher levels make the choice of which one to focus on consciously. (But see here). It has been thought that by the time processing reaches the very high level of the face cells, they only activate when a face is being consciously perceived. But that was not the case here. The authors find that these cells, when tested more densely than has been possible before, show activity corresponding to both images. The face could be read using one filter on these neurons, but a large fraction (1/4 to 1/3) could be read by another filter to represent the non-face image. So by this work, this level of visual processing in the inferotemporal cortex is biased by conscious perception to concentrate on the conscious image, but that is not exclusive- the cells are not entirely representative of consciousness. This suggests that whatever consciousness is takes place somewhere else, or at a selective ensemble level of particular oscillations or other spike coding schemes.

"We trained a linear decoder to distinguish between trial types (A,B) and (A,C). Remarkably, the decoding accuracy for distinguishing the two trial types was 74%. For comparison, the decoding accuracy for distinguishing (A, B) versus (A, C) from the same cell population was 88%. Thus, while the conscious percept can be decoded better than the suppressed stimulus, face cells do encode significant information about the latter. ... This finding challenges the widely-held notion that in IT cortex almost all neurons respond only to the consciously perceived stimulus."

 

The second paper used EEG on human subjects to test their visual and perceptual response to disappearing images and filled-in zones. We have areas in our visual field where we are physically blind, (the fovea), and where higher levels of the visual system "fill in" parts of the visual scene to make our conscious perception seem smooth and continuous. The experimenters came up with a forbiddingly complex visual presentation system of calibrated dots and high-frequency snow whose purpose was to oppose visual attention against conscious perception. When attention is directed to the blind spot, that is precisely when the absence of an image there becomes apparent. This allowed the experimenters to ask whether the typical neural signatures of high-level visual processing (the steady-state visually evoked potential, or SSVEP) reflect conscious perception, as believed, or attention or other phenomena. They presented and removed image features all over the scene, including blind spot areas. What they found was that the EEG signal of SSVEP was heightened as attention was directed to the invisible areas, exactly the opposite of what they hypothesized if the signal was tied to actual visual conscious perception. This suggested that this particular signal is not a neural correlate of consciousness, but one of attention and perhaps surprise / contrast instead.

So where are the elusive neural correlates of consciousness? Papers like these refine what and where it might not be. It seems increasingly unlikely that "where" is the right question to ask. Consciousness is graded, episodic, extinguishable in sleep, heightened and lowered by various experiences and drugs. So it seems more like a dynamic but persistent pattern of activity than a locus, let alone an homunculus. And what exactly that activity is.. a Nobel prize surely awaits someone on that quest.

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Why we Have Sex

Eukaryotes had to raise their game in the sex department.

Sex is very costly. On a biological level, not only does one have to put up with all the searching, displaying, courting, sharing, commitment, etc., but one gives up the ability to have children alone, by simple division, or parthanogenesis. Sex seems to be a fundamental development in the earliest stages of eukaryotic evolution, along with so many other innovative features that set us apart from bacteria. But sex is one of the oddest innovations, and demands its own explanation. 

Sex and other forms of mating confer one enormous genetic benefit, which is to allow good and bad mutations to be mixed up, separated, and redistributed, so that offspring with a high proportion of bad genes die off, and other offspring with a better collection can flourish. Organisms with no form of sex (that are clonal) can not get rid of bad mutations. Whatever mutations they have are passed to offspring, and since most mutations are bad, not good, this leads to a downward spiral of genetic decline, called Muller's ratchet.

It turns out that non-eukaryotes like bacteria do mate and recombine their genomes, and thus escape this fate. But their process is not nearly as organized or comprehesive as the whole-genome re-shuffling and mating that eukaryotes practice. What bacteria do is called lateral gene transfer, (LGT), because it typically involves short regions of their genomes, (a few genes), and can accept DNA from any sort of partner- they do not have to be the same species, though specific surface structures can promote mating within a species. Thus bacteria have frequently picked up genes from other species- the major limitation happens when the DNA arrives into the recipient cell, and needs to find a homologous region of the recipient's DNA. If it is too dissimilar, then no genetic recombination happens. (An exception is for small autonomous DNA elements like plasmids, which can be transferred wholesale without needing an homologous target in the recipient's genome. Antibiotic resistance genes are frequently passed around this way, for emergency selective adaptation!) This practice has a built-in virtue, in that the most populous bacteria locally will be contributing most of the donor DNA, so if a recipient bacterium wants to adapt to local conditions, it can do worse than try out some local DNA. On the other hand, there is also no going back. Once a foreign piece of DNA replaces the recipient's copy, there are no other copies to return to. If that DNA is bad, death ensues.

Two bacteria, connected by a sex pilus, which can conduct small amounts of DNA. This method is generally used to transfer autonomous genetic elements like plasmids, whereas environmental DNA is typically taken up during stress.

A recent paper modeled why this haphazard process was so thoroughly transformed by eukaryotes into the far more involving process we know and love. The authors argue that fundamentally, it was a question of genome size- that as eukaryotes transcended the energetic and size constraints of bacteria, their genomes grew as well- to a size that made the catch-as-catch-can mating strategy unable to keep up with the mutation rate. Greater size had another effect, of making populations smaller. Even with our modern billions, we are nothing in population terms compared to that of any respectable bacterium. This means that the value of positive mutations is higher, and the cost of negative mutations more severe, since each one counts for more of the whole population. Finding a way to reshuffle genes to preserve the best and discard the worst is imperative as populations get smaller.

Sex does several related things. The genes of each partner recombine randomly during meiosis, at a rate of a few recombination events per chromosome, thereby shuffling each haploid chromosome that was received from its parents. Second, each chromosome pair assorts randomly at meiosis, thereby again shuffling the parental genomes. Lastly, mating combines the genomes of two different partners (though inbreeding happens as well). All this results in a moderately thorough mixing of the genetic material at each generation. The resulting offspring are then a sampling of the two parental (and four grand-parental) genomes, succeeding if they get mostly the better genes, and not (frequently dying in utero) if they do not.

Additionally, eukaryotic sex gave rise to the diploid organism, with two copies of each gene, rather than the one copy that bacteria have. While some eukaryotes spend most of their lives in the haploid phase, and only briefly go through a diploid mated state, (yeasts are a good example of this lifestyle), most spend the bulk of their time as diploids, generating hapoid gametes for an extremely brief hapoid existence. The diploid provides the advantage of being able to ignore many deleterious genes, being a "carrier" for all those bad (recessive) mutations that are covered by a good allele. Mutations do not need to be eliminated immediately, taking a substantial load off the mating system to bring in replacements. (Indeed, some bacteria respond to stress by increasing promiscuity, taking in more DNA in case a genetic correction is needed, in addition to increasing their internal mutation rate.) A large fund of defective alleles can even become grist for evolutionary innovation. Still, for the species to persist, truly bad alleles need to be culled eventually- at a rate faster than that with which they appear.

The authors do a series of simulations with different genome sizes, mutation rates and sizes (DNA length) and rates of lateral gene transfer. Unfortunately, their figures are not very informative, but the logic is clear enough. The larger the genome, the higher the mutation load, assuming constant mutation rates. But LGT is a sporadic process, so correcting mutations takes not just a linearly higher rate of LGT, but some exponentially higher rate- a rate that is both insufficient to address all the mutations, but at the same time high enough to be both impractical and call into question what it means to be an individual of such a species. In their models, only when the length of LGT segments is a fair fraction of the whole genome size, (20%), and the rate quite high, like 10% of all individuals experiencing LGT once in their lifetimes, do organisms have a chance of escaping the ratchet of deleterious mutations.

" We considered a recombination length L = 0.2g [genome size], which is equivalent to 500 genes for a species with genome size of 2,500 genes – two orders of magnitude above the average estimated eDNA length in extant bacteria (Croucher et al., 2012). Recombination events of this magnitude are unknown among prokaryotes, possibly because of physical constraints on eDNA [environmental DNA] acquisition. ... In short, we show that LGT as actually practised by bacteria cannot prevent the degeneration of larger genomes. ... We suggest that systematic recombination across the entire bacterial genomes was a necessary development to preserve the integrity of the larger genomes that arose with the emergence of eukaryotes, giving a compelling explanation for the origin of meiotic sex."

But the authors argue that this scale of DNA length and frequency of uptake are quite unrealistic for actual bacteria. Bacterial LGT is constrained by the available DNA in the environment, and typically takes up only a few genes-worth of DNA. So as far as we know, this is not a process that would or could have scaled up to genomes of ten or one hundred fold larger size. Unfortunately, this is pretty much where the authors leave this work, without entering into an analysis of how meiotic recombination and re-assortment would function in these terms of forestalling the accumulation of deleterious mutations. They promise such insights in future work! But it is obvious that eukaryotic sex is in these terms an entirely different affair from bacterial LGT. Quite apart from featuring exchange and recombination across the entire length of the expanded genomes, it also ensures that only viable partners engage in genetic exchange, and simultaneously insulates them from any damage to their own genomes, instead placing the risk on their (presumably profuse) offspring. It buffers the effect of mutations by establishing a diploid state, and most importantly shuffles loci all over these recombined genomes so that deleterious mutations can be concentrated and eliminated in some offspring while others benefit from more fortunate combinations.

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