New anthropology syllabi for 2017

This Fall I’m teaching three courses at Vassar, two in Anthropology and one in Environmental Studies. Syllabi are posted to my Teaching page in case anyone wants to use them – here are the highlights:

Anth 235: Central Asian Prehistory

Anth 235 site map

I taught this for the first time last Spring, so the Fall syllabus is updated based on how things went in the first go around. This time, students will get more more in depth with the fossil hominins and less on the lithics on the early side. On the more recent end, there are now readings expressly concerned with sites of the Bactrian-Margiana Archaeological Complex, as well as archaeology of both the Tarim and Pazyryk mummies.

Anth 305: Human Evolutionary Developmental Biology

cropped-zevodevo1.jpg

This is a seminar version of the first class I ever made on my own, previously taught at the University of Michigan and Nazarbayev University. There have been lots of new discoveries and I’ve published more on this topic since the last time I taught the class. I’m  also excited to see how this class goes as a seminar in which students contribute more to discussion, rather than me rambling on about osteoblasts, morphological integration, and the like.

Enst 187: A Prehistoric Perspective on Climate Change

climatesummit

This is a 100% brand spankin new class, that uses the climate-denialist argument, “But climate has always been changing,” as a basis for comparing the past and the present. In this First-year Writing Seminar, we’ll compare arguments for defining the “Anthropocene,” examine how climate change may have impacted human evolution, and study archaeological evidence for how climate change has impacted different prehistoric societies.

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#AAPA2017 – Modularity & evolution of the human canine

I’m recently returned from this year’s AAPA Conference, hosted by Tulane University in New Orleans. What a trip!

Usually my presentations involve fossils and/or growth, but this year I wanted to try a different way of looking at the evolution & development – integration & modularity. In short, biological structures that share a common developmental background and/or function may comprise ‘modules’ that are highly ‘integrated’ with one another, but relatively less integrated with other structures or modules.

I hypothesized that canine reduction in hominins is a result of a shift in modularity of the dentition, such that the canine became more highly integrated with the incisors than with the premolars. I’d thought of this 5 years ago when creating the first rendition of my human evo-devo course (offering again next fall!), but never got to look into it. Interestingly, the results generally supported my predictions, except for one pesky sample…

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As my primatologist friends will tell you, male chimps are the worst.

Here’s a pdf version of the poster. It was fun to dabble with a new methodology, to see my far-flung friends, and to visit a fun historic place for the AAPA conference. Definitely looking forward to next year in Austin!

Did Neandertal brains grow like humans’ or not?

According to Marcia Ponce de Leon and colleagues, “Brain development is similar in Neandertals and modern humans.” They reached this conclusion after comparing how the shape of the brain case changes across the growth period of humans and Neandertals. This finding differs from earlier studies of Neandertal brain shape growth (Gunz et al. 2010, 2012).

Although Neandertals had similar adult brain sizes as humans do today, the brains are nevertheless slightly different in shape:

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Endocranial surfaces of a human (left, blue) and Neandertal (right, red), from Gunz et al. (2012). These surfaces reflect the size and shape of the brain, blood vessels, cerebrospinal fluid, and meninges.

Gunz et al. (2010, 2012) previously showed that endocranial development in humans, but not in Neandertals or chimpanzees, has a “globularization phase” shortly after birth: the endocranial surface becomes overall rounder, largely as a result of the expansion of the cerebellum:

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Endocranial (e.g., brain) shape change in humans (blue), Neandertals (red) and chimpanzees (green), Fig. 7 from Gunz et al. (2012). Age groups are indicated by numbers. The human “globularization phase” is represented by the great difference in the y-axis values of groups 1-2 (infants). The Neandertals match the chimpanzee pattern of shape change; Neandertal neonates (LeM2 and M) do not plot as predicted by a human pattern of growth.

Ponce de Leon and colleagues now challenge this result with their own similar analysis, suggesting similar patterns of shape change with Neandertals experiencing this globularization phase as well (note that endocranial shapes are always different, nevertheless):

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Endocranial shape change in humans (green) and Neandertals (red), from Ponce de Leon et al. (2016). Note that the human polygons and letters represent age groups, whereas the Neandertal polygons and labels are reconstructions of individual specimens.

The biggest reason for the difference between studies is in the fossil sample. Ponce de Leon et al. have a larger fossil sample, with more non-adults including Dederiyeh 1-2, young infants in the age group where human brains become more globular.

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Comparison of fossil samples between the two studies.

But I don’t think this alone accounts for the different findings of the two studies. Overall shape development is depicted in PC 1: in general, older individuals have higher PC1 scores. The globularization detected by Gunz et al. (2010; 2012) is manifest in PC2; the youngest groups overlap entirely on PC1. The biggest difference I see between these studies is where Mezmaiskaya, a neonate, falls on PC2. In the top plot (Gunz et al., 2012), both Mezmaiskaya and the Le Moustier 2 newborn have similar PC2 values as older Neandertals. In the bottom plot (Ponce de Leon et al., 2012), the Mezmaiskaya neonate has lower PC2 scores than the other Neandertals. Note also the great variability in Mezmaiskaya reconstructions of Ponce de Leon et al. compared with Gunz et al.; some of the reconstructions have high PC2 values which would greatly diminish the similarity between samples. It’s also a bit odd that Engis and Roc de Marsal appear “younger” (i.e., lower PC1 score) than the Dederiyeh infants that are actually a little bit older.

Ponce de Leon et al. acknowledge the probable influence of fossil reconstruction methods, and consider other reasons for their novel findings, in the supplementary material. Nevertheless, a great follow-up to this, to settle the issue of Neandertal brain development once and for all, would be for these two research teams to join forces, combining their samples and comparing their reconstructions.

REFERENCES

ResearchBlogging.org

Gunz P, Neubauer S, Maureille B, & Hublin JJ (2010). Brain development after birth differs between Neanderthals and modern humans. Current Biology : 20 (21) PMID: 21056830

Gunz P, Neubauer S, Golovanova L, Doronichev V, Maureille B, & Hublin JJ (2012). A uniquely modern human pattern of endocranial development. Insights from a new cranial reconstruction of the Neandertal newborn from Mezmaiskaya. Journal of Human Evolution, 62 (2), 300-13 PMID: 22221766

Ponce de León, M., Bienvenu, T., Akazawa, T., & Zollikofer, C. (2016). Brain development is similar in Neanderthals and modern humans Current Biology, 26 (14) DOI: 10.1016/j.cub.2016.06.022

Updated bioanthro syllabi

This term I’m teaching two of my favorite classes, and I’ve updated their syllabi on my Teaching page. First is a 200-level class about human biological variation and issues surrounding race.  Second is my baby, a 300-level on human evolutionary developmental biology. If you want to teach these kinds of classes but don’t want to reinvent the wheel, feel free to use these syllabi to develop your own!

Here are the course descriptions:

Ant 263: Humans and Race
This course examines the nature of human biological variation, in the contexts of genetics, anatomy, history, and society. Students will learn about why humans vary, what this variation does and does not tell us about people, and the ways in which social inequality becomes manifest in human biology. The course will begin by surveying biological variation, both adaptive and selectively neutral, in humans. We will then focus on what the term ‘race’ means biologically, and why this concept does not describe human variation. Moving from biology and genetics, we examine psychological and historical origins of racialist thinking in the United States. This historical overview segues into an analysis of how racial categories are used in biomedical research today. Through the framework of the developmental origins of health and disease, we review the biological mechanisms whereby social inequality results in health disparity.

Ant 364: Human Evolutionary Developmental Biology
What literally makes us human? This class will examine how growth and development were modified over the course of human evolution, to create the animals that we are today. Human anatomy is placed in an evolutionary context by comparison with living primates and the human fossil record. The first half of the course focuses on theory, namely evolution, genetics and life history. The second half examines evidence for the development and evolution of specific parts of the body, from head to toe.

Did GDF6 “gene tweak” allow humans to become upright?

The short answer is, “Not really.” But as is often the case, the real story behind so many headlines last week is a bit more complicated.

smh.

smh. Links to the first, second, third, and fourth stories.

What are they talking about, Willis?

These headlines, each saying something slightly different, are referring to a study by Indjeian and colleagues published in Cell.  Researchers identified a stretch of DNA that is highly conserved across mammals, or in other words, it is very similar between very different organisms. In humans, however, this conserved region is actually missing (“hCONDEL.306”):

Fig. 4A from Indjeian et al. 2016. A stretch of DNA, "hCONDEL.306" is completely missing in humans (as is another stretch, hCONDEL.305) but otherwise very similar between chimpanzees, monkeys and mice.

Fig. 4A from Indjeian et al. 2016. A stretch of DNA on Chromosome 8, “hCONDEL.306,” is very similar between chimpanzees, macaque monkeys, and mice, but is completely missing in humans (as is another stretch, hCONDEL.305).

That a stretch of DNA should be highly conserved across diverse animal groups suggests purifying natural selection has prevented any mutations from occurring here – alterations to this stretch of DNA negatively affected fitness. But that humans should be missing such a highly conserved region suggests that this deletion came under positive natural selection at some point in human evolution. This strategy, of seeking stretches of DNA that are similar between many animals but very different in humans, has led to the identification of hundreds of genetic underpinnings of human uniqueness. Some of these, such as the case in question, involve deleted sequences and have been termed “hCONDELs,” for “regions with high sequence conservation that are surprisingly deleted in humans” (McLean et al., 2011: 216). Others involve the accumulation of mutations where other animals show few or none (e.g., HACNS1; Prabhakar et al. 2008). In many (most?) cases these are “non-coding” sequences of DNA.

How can “non-coding” DNA help make humans upright?

As was predicted 30 years ago (King and Wilson, 1975), what makes humans different from other animals isn’t so much in the protein-coding DNA (the classical understanding of the term, “genes”), but rather in the control of these protein-coding genes. “Non-coding” means that a stretch of DNA may get transcribed into RNA but is not then translated into proteins. But even though these sequences themselves don’t become anything tangible, many are nevertheless critical in regulating gene expression – when, where and how much a gene gets used. It’s wild stuff. Indeed, “Many human accelerated regions are developmental [gene] enhancers” (Capra et al., 2013).

In the present case, hCONDEL.306 refers to the human-specific deletion of a developmental enhancer located near the GDF6 gene, which is a bone morphogenetic protein. The major finding of the paper, as stated succinctly in the Highlights title page, is that “Humans have lost a conserved regulatory element [hCONDEL.306] controlling GDF6 expression…. Mouse phenotypes suggest that [this] deletion is related to digit shortening in human feet.”

How do they link this “gene tweak” to digit shortening?

Since humans have lost this gene enhancer that is highly conserved in other mammals, Indjeian and team reasoned that the chimpanzee DNA sequence associated with this deletion, retaining the enhancer sequence, is likely the ancestral condition from which the human version evolved. They inserted the chimpanzee version into mouse embryos and watched what happened as they developed. The enhancer was only active in the mice’s back legs, specifically in the cartilage that would later become the lateral toe bones and cells that would become a muscle of the big toe (abductor hallucis). These are areas where humans and chimpanzees differ: our lateral toes are shorter than chimps’, and we only have one abductor hallucis muscle whereas chimpanzees have an additional, longer abductor hallucis  (Aiello and Dean, 2002). So, we’re on our way to seeing how hCONDEL.306 might relate to our big toe or upright walking, as the headlines say.

But this still doesn’t explain how this deletion affects GDF6 gene expression, and therefore what this does for our feet. Pressing onward, the scientists compared the size of certain bones in mice with a normal Gdf6 gene, and those in which the Gdf6 gene was completely turned off (or “knocked out”).  The Gdf6 knock-out mice had shorter lateral toe bones than regular mice, but they also had shorter big toes as well – the previous experiment staining mouse embryos showed the ancestral enhancer was expressed more in the latter toes, not so much the big toe.

Figures 5-6 from Indjeian et al. (2016) sum up the findings. Figure 5 (left) shows that the ancestral version of the GDF6 enhancer (blue staining) is most strongly expressed in the lower limb, especially the fifth toe bone. Figure 6 (right) shows that a lack of GDF6 expression (black bars) results in shorter skull and toe bones. Combining these findings, humans lack a gene enhancer associated with the development of long lateral toes.

Figures 5-6 from Indjeian et al. (2016) sum up the findings. Figure 5 (left) shows that the ancestral version of the GDF6 enhancer (blue staining) is most strongly expressed in the lower half of the body, especially the fifth toe bone. Figure 6 (right) shows that a lack of Gdf6 expression (black bars) results in shorter skull and toe bones. Combining these findings, humans lack a gene enhancer associated with the development of long lateral toes.

hCONDEL.306 doesn’t completely turn off GDF6, so this second experiment doesn’t really tell us exactly what the hCONDEL does. But the results are highly suggestive. Indjeian and team showed that Gdf6 affects toe length, among other skeletal traits, in mice. The ancestral enhancer that humans are missing seems to affect GDF6 activity in the leg/foot only. This illustrates a mechanism of modularity – as the authors state, “Loss of this enhancer would thus preserve normal GDF6 functions in the skull and forelimbs, while confining any … changes to the posterior digits of the hindlimb.” In other words, developmental enhancers allow different parts of the body to evolve independently despite being made by some of the same genes (such as GDF6).

As with any good study, results are intriguing but they raise more questions for future studies. The researchers conducted two experiments to investigate the function of hCONDEL.306: first putting the chimp version in mouse embryos to see where the ancestral enhancer is expressed, and then turning off Gdf6 completely in mice to see what happens. A more direct way to see what hCONDEL.306 does might be to put a longer stretch of the human sequence surrounding GDF6 containing (or rather missing) the ancestral enhancer into mouse embryos. I’m not a molecular biologist so maybe this isn’t possible. But this is important because the ancestral (chimpanzee) enhancer appeared to be most strongly expressed in the little toe, but of course this isn’t our only toe that is short compared to chimps. Similarly, how hCONDEL.306 relates to the abductor hallucis muscle remains in question – does it reduce the size of the intrinsic muscle present in both humans and chimps, or does it prevent development of the longer muscle that chimps have but we lack? We can expect to find hCONDEL.306 in the genomes of Neandertals (and Denisovans?), since they also have short toes, but what would it mean if they retained the ancestral enhancer?

So how does this gene tweak help with upright walking?

This is a really cool paper with important implications for human evolution, but something seems to have been lost in translation between the paper and the headlines (the news pieces themselves are good, though). The upshot of the study is that humans lack a stretch of non-coding DNA, which in chimpanzees (or chimp-ified mice) promotes embryonic development of the lateral toes and a big toe muscle. This may be a genetic basis for at least some aspects of our unique feet that have evolved under natural selection for walking on two legs.

But the headlines misrepresent this result, with words like “led to,” “allowed,” and “caused,” especially when these are followed by “big toe” or “upright walking.” hCONDEL.306 doesn’t really have anything to the big toe bone itself, although it might relate to a muscle affecting our big toe. The only sense in which the “Gene tweak led to humans’ big toe” (first title above) is that hCONDEL.306 might be responsible for our short lateral toes, which make our first toe look big by comparison. The other headlines are misleading since we know from fossil evidence that hominins walked upright long before we have evidence for short toes:

These little piggies get none. Fourth toe bones of living apes and humans (left) and possible hominins from 3-5 million years ago (right).

These little piggies get none. Fourth toe bones of living apes and humans (left) and (probable) hominins from 3-5 million years ago (right). I did my best to get all images to scale.

“Epigenetic,” from the fourth article headline, is simply wrong. Modern day epigenetics is a field concerned with the chemical alterations to the structure of DNA. Even the broad concept of epigenetic as originally devised by Conrad Waddington was about how environments (cellular or outside the body) influence development.

ResearchBlogging.orgIt’s hard to fit all the important and interesting information from scientific papers into news headlines. Still, it would be good if headlines more accurately portrayed scientific findings, especially avoiding such definitive verbs as “caused.” Especially in the realm of biology, people should know that there’s a lot that we still don’t know, that there’s lots more important work left to be done.

References

Aiello and Dean, 2002. Human Evolutionary Anatomy. Academic Press.

Capra et al., 2013. Many human accelerated regions are developmental enhancers. Philosophical Transactions of the Royal Society B 368: 20130025.

Indjeian et al. 2016. Evolving new skeletal traits by cis-regulatory changes in bone morphogenetic proteins. Cell http://dx.doi.org/10.1016/j.cell.2015.12.007

King and Wilson, 1975. Evolution at two levels in humans and chimpanzees. Science 188: 107-116 DOI: 10.1126/science.1090005

McLean et al., 2011. Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature 471: 216-219.

Prabhakar et al., 2008. Human-specific gain of function in a developmental enhancer. Science 321: 1346-1350.

Osteology Everywhere: Ilium Nublar

Jurassic Park is objectively the greatest film ever made, so I don’t need to explain why I recently watched it for the bajillionth time. Despite having seen this empirically excellent movie countless times, I finally noticed something I’d never seen before.

Hold on to your butts. What's that on the screen in front of Ray Arnold?

Hold on to your butts – what’s that on the screen in front of John Arnold? (image credit)

The film takes place on the fictitious island “Isla Nublar,” a map of which features prominently in the computer control room when s**t starts to go down. Here’s a clearer screenshot of one of Dennis Nedry‘s monitors:

Isla Nublar from the JP control room. Quiet, all of you! They’re approaching the tyrannosaur paddock…. (image credit)

It dawned on me that the inspiration for this island is none other than MLD 7, a juvenile Australopithecus africanus ilium from the Makapansgat site in South Africa:

Figure 1 from Dart, 1958. Left side is MLD 7 and right is MLD 25. Top row is the lateral view (from the side) and bottom row is the medial view (from the inside).

Figure 1 from Dart, 1958. Left side is MLD 7 and right is MLD 25. Top row is the lateral view (from the side) and bottom row is the medial view (from the inside). These two hip bones are from the left side of the body (see the pelvis figure in this post). Note the prominent anterior inferior iliac spine on MLD 7, a quintessential feature of bipeds.

Isla Nublar is basically MLD 7 viewed at an angle so that appears relatively narrower from side to side:

MLD at a slightly oblique view (or stretched top to bottom) magically transforms into Isla Nublar.

MLD 7 at a slightly oblique view (or stretched top to bottom) magically transforms into Isla Nublar.

It’s rather remarkable that some of the most complete pelvic remains we have for australopithecines are two juveniles of similar developmental ages and sizes from the same site. In both, the iliac crest is not fused, and joints of the acetabulum (hip socket) hadn’t fused together yet. The immaturity of these two fossils matches what is seen prior to puberty in humans and chimpanzees. Berge (1998) also noted that MLD 7, serving as an archetype for juvenile Australopithecus, is similar in shape to juvenile humans, whereas adult Australopithecus (represented by Sts 14 and AL 288) are much flatter and wider side to side. Berge took this pattern of ontogenetic variation to match an ape-like pattern of ilium shape growth. This suggests a role of heterochrony in the evolution of human pelvic shape, or as Berge (1998: 451) put it, “Parallel change in pelvic shape between human ontogeny and hominid phylogeny.” In layman’s terms, ‘similar changes in both pelvic growth and pelvis evolution.’

Dawn of Paleoepigenomics

It was only a matter of time. In the 1990s scientists started extracting, sequencing and analyzing mitochondrial DNA from Neandertal fossils. In the 2000s they made major advances in obtaining and analyzing ancient nuclear DNA, which is much trickier than mtDNA. In just the past year, paleogeneticists pushed the envelope in sequencing truly ancient DNA, announcing hominin and horse genomes from 400 and 700 thousand years ago, respectively. As I mentioned a few months ago, the burgeoning field of paleogenomics is revealing things about human evolution that could hardly be dreamt of only a few decades ago.

But world of DNA is so much more than just ceaseless sequences of four letters, and the field of ‘epigenetics’ has emerged to investigate the complex way that chemical alterations to DNA structure (not sequence) affect gene expression. Melding epigenetics & paleogenomics, David Gokhmen and colleagues report in Science, “Reconstructing the DNA methylation maps of the Neandertal and the Denisovan.” For a review of what DNA methylation is and does, check out this Scitable overview. In short, DNA methylation is part of the reason why not all of your genes in your genome are expressed at all times throughout your body, even though all of your genes are physically present in all of the cells of your body. Methylation plays an important role in turning genes on or off during development. It’s nuts. Now, the structure of DNA breaks down over time after an animal dies, obscuring original methylation patterns. But the decompositoin process is becoming better understood, including patterns at methylated vs. unmethylated sites. As Gokhmen et al. write, these patterns “may serve as a proxy for the levels of methylation in ancient DNA.”

This brilliant insight allowed Gokhmen and colleagues to identify some 2000 genomic regions in bone cells that differed in methylation between a living human, a Neandertal and a Denisovan (2000 less than 1% of all regions). One such region was the HOXD cluster, which is known to be involved in embryonic limb development. Neandertals and Denisovans were more methylated than humans at the HOXD9 and HOXD10 loci. Whether and how these epigenetic differences might be responsible for anatomical differences between these populations is not at all clear yet. But Neandertals are known to differ from humans in some aspects of arm and leg anatomy – authors point out that Neandertals generally have larger and more robust joints but shorter limbs. They state, “together, these findings suggest that the HOXD cluster might have played a key role in the recent evolution of human limbs.”

Importantly, “Denisovans” are only known from 2 teeth and part of a finger bone, no other limb fossils are known (or at least published) for this ancient population. This leads us to a prediction – if the similarly hypermethylated HOXD sites in Denisova and Neandertals are functionally important, then Denisovan limb fossils, if ever found, should be more like Neandertals than like humans. If this prediction is borne out, this would provide evidence of specifically how HOXD9-10 affect limb development, and how HOXD epigenetic regulation has changed in human evolution. This hypothesis can be tested, but only with the discovery of the right fossils (i.e., genetically attributable to Denisovans). Well, the functional importance of hyper/hypomethylation at these sites could probably also be assessed with transgenic mouse experiments…

There is truly remarkable work being done in paleogenomics – and now paleoepigenomics – which will probably begin to form the basis of some exciting new human evo-devo research.