Continuing the discussion from Uncommon or Common Descent?:
@JoeG had a great question on the science of comparative biology:
What are the mechanisms scientists have uncovered that explain the anatomical and physiological differences between humans and chimpanzees?
This is a great question, and there is just so much to cover here. It seemed like it was worth learnign about, and I wanted to pose the question here to the whole community.
One place to start is this thread (Human Gene for Big Brain), and all the papers it references. We have been learning an immense amount about how human brains are different then chimps.
Another thread of equal interest, even though it is not chimps considered, is this paper on Neanderthal minibrains, a technique being developed to understand the functional significance of Neanderthal and Sapiens genetic differences (Growing Neanderthal Minibrains).This one raises some interesting ethical issues too.
3 posts were merged into an existing topic: Missing the Point on Ewert
A post was merged into an existing topic: Missing the Point on Ewert
@swamidass have we fully sequenced the genomes? I donât think we have. Correct me if Iâm wrong
Complex questions. It depends what you mean by âfullyâ.
A post was merged into an existing topic: Missing the Point on Ewert
Amazing progress in just a few decades. Another area of amazing progress has been in the sequencing of ancient genomes of people, animals, plants, viruses and bacteria. This is remaking the historical sciences of archaeology and paleontology.
The head of a chimp is positioned differently on the spine than humans. This requires a change in bone structure and musculature. You cannot do that willy-nilly. It takes planning and foresight. The same goes for other muscles, too. With chimps the attachment points for their muscles are different from ours. Again, that doesnât happen willy-nilly and I doubt anyone can show that using the same genes differently can allow for that affect.
Kinesiology- that was one of my fields of study. I am far from an expert but I know it matters where and how muscles attach to bones and it is a given it doesnât happen by chance.
Brain size- you need to coordinate with the size of the cranium- the entire head and face needs to be restructured to get a human from chimp-like ancestors.
You canât talk about anatomical differences between species without mentioning evolutionary developmental biology (evo-devo). So hereâs one of my favourite evo-devo papers, which just so happens to be on this very topic:
Prescott, S. L., Srinivasan, R., Marchetto, M. C., Grishina, I., Narvaiza, I., Selleri, L., ⌠Wysocka, J. (2015). Enhancer Divergence and cis-Regulatory Evolution in the Human and Chimp Neural Crest. Cell, 163(1), 68â84.
http://www.cell.com/abstract/S0092-8674(15)01088-0
The vast majority of anatomical differences between species are the result of changes to regulatory elements, not protein-coding genes themselves. Rather than changing an amino acid in a protein such that its activity is changed slightly, far more important are changes to the spatio-temporal expression of a suite of genes.
Therefore, we gain a huge insight by studying genetic enhancers, one of the major types of regulator elements. This paper analysed the epigenomic profile of human and chimp cranial neural crest cells (iPSCs from each species with this identity), looking for differences in how genes were expressed. They then mapped these differences to the enhancer elements that control these epigenomic profiles. They found that these differences in profiles (how the different enhancers controlled expression) was largely explained by sequence differences in the enhancer elements themselves. Not many sequence differences either - about 3-6 nucleotide differences per 500bp enhancer. These sequence changes result in differential enhancer activity (and therefore differences in gene expression) by changing the binding affinity of the site for different transcription factors.
If a site loses binding affinity for transcription factor A, then it might fail to be activated in tissue A (that expresses TF A). If the site gains binding affinity for transcription factor B, it might now be activated in tissue B (that expresses TF B).
Using this technique, the authors identifed several hundred enhancers with differential activity between humans and chimps, and found that many of these enhancers are associated with (control the expression of) genes that are differentially expressed between humans and chimps. Many phenotypes associated these genes affect aspects of head morphology that are divergent between humans and chimps such as the size of the mandible and maxilla, skull shape, and pigmentation.
To paraphrase from the paper:
âFor example, PAX3 and PAX7 are expressed at higher levels in chimps and are associated with clusters of chimp-biased enhancers. In mice, mutations of these TFs lead to a reduction of pigmentation and snout length (Pax3), and reduction of the maxilla and pointed snout (Pax7). These features are consistent with small jaw size and hypo pigmentation of humans compared to chimps. Genetic variants at the PAX3 locus have been identified in GWAS studies as regulators of normal-range facial shape.â
To make a long story short, and to tie it back to the original question, this study showed that differential activity of enhancers likely explains a huge amount of the differences between human and chimps in terms of craniofacial morphology. Since this differential activity is largely the result of a handful of changes to the nucleotide sequences of each of these enhancer elements, we can say that a relatively small number of mutations explain a large proportion of our differing craniofacial morphology.
Itâs a similar story with muscle attachments. This is actually related to my own work, although Iâm far from an expert in it. Put very simply, muscle attachment sites are defined by tendon precursor cells. Tendon precursors are induced at a particular site along the cartilage (which will become the bone), and secrete signalling factors that guide muscles cells to them. Where along the cartilage these tendon precursors appear is determined by, as mentioned earlier, differential gene expression. A classic example is having gradients of 2 different secreted factors, one secreted by cell population A (say, on the left), and the other secreted by cell population B (on the right). In the middle, between the sources of these secreted factors, there will be equal prescence of secreted factors and A and B, while their presence tails off towards the right and left, respectively. If a perfect balance between secreted factors A and B is required for the expression of a particular gene that will cause the cell to differentiate into a tendon precusor cell, then in this example, the tendon (and muscle attachment site) will form in the middle of cartilage. Now lets say a mutation in one of the enhancers for the gene that produces secreted factor A occurs which decreases the expression of the gene. Less secreted factor A will be produced as a result. Now the gradients are shifted, and now the location along the cartilage with equal levels of secreted factors A and B is no longer in the middle, itâs now shifted to the left. Now the muscle attachment site will appear closer to the left side of this cartilage, rather than the middle.
This is a very simplified model of how muscle attachment sites (and other differentiated cell populations) have the positions defined, and how these can change.
Finally, to touch on Joeâs objection that these kinds of changes have to be coordinated (e.g. canât change the brain size without changing the cranium size), itâs actually the case that development is remarkably plastic. For example, in terms of mechanical forces. It would be disastrous if it were any other way. Just think of the human variation in things like brain/cranium size, long bone head (the part that interfaces with a joint) size, eyeball size, etc. These sizes and precise shapes donât differ between people in such a way that theyâre genetically coordinated with the rest of the body, or nearby associated structures. They all fit together during development. As tissues interact at their borders they accomodate each other, to a certain extent. As the brain grows during development, it âpushesâ against the tissue that will form the cranium (remember itâs not a rigid bone at this point). At the same time, the tissue that will form the cranium pushes back against the brain, and they find a balance somewhere in the middle such that the brain perfectly fits within the cranium.
Excellent point. It is one of the big surprises of biology.
I just realised how garbled the second sentence there was. Thank goodness for the edit function.
Well, that regulatory elements appear to change more rapidly and experience more plasticity was know in bacteriology for some time. After all, thatâs where the most complete sequencing and best understood gene expression mechanisms were first worked out. But todayâs students often donât even start off learning about yeasts⌠Oh no, now itâs all Zebra fish, nematodes and Drosophila. And it doesnât help that most journals articles pre-1980 exist as images and not searcheable text. Kids these days⌠Probably never poured a gradient SDS-PAGE gel themselves, let alone ran a cesium chloride, ultracentrifuge step to clean up the DNA.
I have read Sean Carroll and Shubin. They havenât found what it is that determines what will develop. Also thinking that blind watchmaker evolution can produce such regulatory networks in the first place stretches credibility. This is the same ole âusing the same genes differentlyâ promissory note. We have talked about evo-devo. Read Dr Denton said about it:
To understand the challenge to the âsuperwatchâ model by the erosion of the gene-centric view of nature, it is necessary to recall August Weismannâs seminal insight more than a century ago regarding the need for genetic determinants to specify organic form. As Weismann saw so clearly, in order to account for the unerring transmission through time with precise reduplication, for each generation of âcomplex contingent assemblages of matterâ (superwatches), it is necessary to propose the existence of stable abstract genetic blueprints or programs in the genes- he called them âdeterminantsâ- sequestered safely in the germ plasm, away from the ever varying and destabilizing influences of the extra-genetic environment.
Such carefully isolated determinants would theoretically be capable of reliably transmitting contingent order through time and specifying it reliably each generation. Thus, the modern âgene-centricâ view of life was born, and with it the heroic twentieth century effort to identify Weismannâs determinants, supposed to be capable of reliably specifying in precise detail all the contingent order of the phenotype. Weismann was correct in this: the contingent view of form and indeed the entire mechanistic conception of life- the superwatch model- is critically dependent on showing that all or at least the vast majority of organic form is specified in precise detail in the genes.
Yet by the late 1980s it was becoming obvious to most genetic researchers, including myself, since my own main research interest in the â80s and â90s was human genetics, that the heroic effort to find information specifying lifeâs order in the genes had failed. There was no longer the slightest justification for believing there exists anything in the genome remotely resembling a program capable of specifying in detail all the complex order of the phenotype. The emerging picture made it increasingly difficult to see genes as Weismannâs âunambiguous bearers of informationâ or view them as the sole source of the durability and stability of organic form. It is true that genes influence every aspect of development, but influencing something is not the same as determining it. Only a small fraction of all known genes, such as the developmental fate switching genes, can be imputed to have any sort of directing or controlling influence on form generation. From being âisolated directorsâ of a one-way game of life, genes are now considered to be interactive players in a dynamic two-way dance of almost unfathomable complexity, as described by Keller in The Century of The Gene- Michael Denton âAn Anti-Darwinian Intellectual Journeyâ, Uncommon Dissent (2004), pages 171-2
Everything you posted argues against blind watchmaker evolution. Great they are finding out there are differences in the way genes are expressed.
Put very simply, muscle attachment sites are defined by tendon precursor cells.
OK, that doesnât mean the blind watchmaker did it.
Finally, to touch on Joeâs objection that these kinds of changes have to be coordinated (e.g. canât change the brain size without changing the cranium size), itâs actually the case that development is remarkably plastic.
Yes, by design
Making me feel my age today. Iâve done all of the above. I had a bad dream a few years ago in which I was frustrated trying to extract chloroplasts in a cesium chloride gradient. Of course, I was frustrated back when I was actually doing trying to do it. Oh, the lengths we would go to purify plastid DNA back then.
What do you mean by this? That we havenât mapped out literally every signalling pathway and every regulatory network? Because of course we havenât, but how is that relevant?
How? You didnât engage with anything I said at all. And what is âblind watchmaker evolutionâ as opposed to the theory of evolution?
I didnât say that it did⌠You said changes in muscle attachment sites doesnât âhappen willy-nillyâ (by which I presume you meant couldnât evolve naturally), so I explained the basics of how muscle attachment sites are determined, and therefore how they can change - by using the same genes differently.
You can say itâs by design if you like, but that doesnât change the fact that it answers your objection about all these changes needing to be coordinated. If it was designed then the designer did it in such a way that the system could naturally evolve.