You can’t talk about anatomical differences between species without mentioning evolutionary developmental biology (evo-devo). So here’s 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), 68–84.
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:
“For 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.”
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.
It’s a similar story with muscle attachments. This is actually related to my own work, although I’m 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, it’s 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 Joe’s objection that these kinds of changes have to be coordinated (e.g. can’t change the brain size without changing the cranium size), it’s 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 don’t differ between people in such a way that they’re 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 “pushes” against the tissue that will form the cranium (remember it’s 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.