Genetics

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

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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.

Is it worth seeking a genetic basis for math genius?

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The topic this week in my Human Variation and Race class is intelligence. We’ve read about and discussed what intelligence is, how it is quantified, and the extent to which ‘intelligence,’ however defined, is biologically and/or environmentally determined. Intelligence (test score) has been shown to be heritable, meaning that a proportion of the variation in IQ test scores in a population can be explained by genetic variation. But that is not the same as saying that it is genetically determined. Similarly, complex traits such as intelligence, behaviors, and diseases almost never have a simple genetic basis – a common theme over at the Mermaid’s Tale, one that seems too rarely heeded. So you can imagine my surprise and delight at finding this news piece just published in Nature: “Root of maths genius sought: Entrepreneure’s ‘Project Einstein’ taps 400 top academics for their DNA.” Of course “roots” meant “genes.”

Apparently, bioinformatics entrepreneur and multimillionaire Jon Rothberg has set out to identify the genetic bases of peak mathletics, by analyzing the genomes of hundreds of mathematicians and physicists. Good luck, buddy! My initial reaction was to be appalled that an educated biologist these days could be such a flagrant biological determinist. What’s more, when approached about participating in the study, mathematician Curtis McMullen asked about the ethics of the project and its outcomes: “The uniform answer to my questions was that ‘we are not responsible for how the information is used after the study is completed.'” Ew. The project as briefly described reeked of some eugenics programme.

My prediction is that if this study takes off, Rothberg & buddies will be horribly disappointed. Assuming they are able to identify any genetic variants, these will probably only explain a small amount of variation in “maths genius.” Which itself is problematic, since there is probably not a single manifestation of math genius, and even if there were a single way to be a math genius, there may be several genetic pathways relating to the phenotype (not an uncommon finding of many genome-wide association studies). But hey, it seems to be Rothberg’s own money going into the study, so why not.

But then, if my prediction were to hold, this wouldn’t necessarily be a failure – it would point to an important role of society and learning environment in shaping individuals’ mathematic capability. And then maybe big money could begin to be diverted to more productive programs investigating and improving how people learn, rather than to large scale projects seeking simple answers when there isn’t necessarily any reason to expect them in the first place.

Speciation and reticulation

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ResearchBlogging.org Hey, “all you lovers out there,” which is how Marvin Berry introduced “Earth Angel” at the Enchantment Under the Sea dance back in good-olde 1955. And by “lovers” I mean “geneticists.”

Poring over the recent Neandertal nuclear genome paper (Green et al. 2010) for seminars, we’re struck by two contradictory ideas. On the one hand, the authors demonstrate pretty convincingly that Neandertals and the more ‘anatomically modern’ humans of Europe and Asia interbred. This doesn’t come from genetic comparisons of Neandertal and contemporaneous human fossils, but of Neandertals with living humans traipsing modern soil. But on the other hand, the authors estimate the time of the divergence of Neandertal and living human populations.
Herein lies the rub:

“Population divergence [is] defined as the point in time when two populations last exchanged genes.” (Green et al. 2010: 717)

Which they estimate, based on genome sequence divergence and some other assumptions, to be anywhere from ~270,000 – 440,000 years ago. But then this:

“[The Out-of-Africa] model for modern human origins suggests that all present-day humans trace all their ancestry back to a small African population that expanded and replaced [Neandertals] without admixture. Our analysis of the Neandertal genome may not be compatible with this view because Neanertals are on average closer to individuals in Eurasia…” (Green et al. 2010: 721)

Though they say “may not” they probably should’ve just said “isn’t.” Either way, they estimate an ancient date at which the groups in question “last exchanged genes,” but also demonstrate that these populations last exchanged genes much more recently.
So what is “population divergence,” then? As a wise man asked, “what does divergence mean when there is reticulation?” (I’m assuming he would prefer to go nameless) Reticulation referring not to pythons or chipmunks, but to mating between individuals in different populations. Is “divergence” not so much the last time genes were exchanged, but rather the time when the genomes began to become different?
Now that I bring it up, wouldn’t it also be neat to see a fight between the reticulated python and northern reticulated chipmunk?
Reference
Green, R., Krause, J., Briggs, A., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M., Hansen, N., Durand, E., Malaspinas, A., Jensen, J., Marques-Bonet, T., Alkan, C., Prufer, K., Meyer, M., Burbano, H., Good, J., Schultz, R., Aximu-Petri, A., Butthof, A., Hober, B., Hoffner, B., Siegemund, M., Weihmann, A., Nusbaum, C., Lander, E., Russ, C., Novod, N., Affourtit, J., Egholm, M., Verna, C., Rudan, P., Brajkovic, D., Kucan, Z., Gusic, I., Doronichev, V., Golovanova, L., Lalueza-Fox, C., de la Rasilla, M., Fortea, J., Rosas, A., Schmitz, R., Johnson, P., Eichler, E., Falush, D., Birney, E., Mullikin, J., Slatkin, M., Nielsen, R., Kelso, J., Lachmann, M., Reich, D., & Paabo, S. (2010). A Draft Sequence of the Neandertal Genome Science, 328 (5979), 710-722 DOI: 10.1126/science.1188021

Denisova the Menace II: Nuclear story

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Earlier this year, I discussed the publication of a mitochondrial DNA study from a 50,000 year old pinky bone from Denisova in Siberia. The big story there was that the mtDNA of this specimen was twice as divergent (different) from modern humans as Neandertal mtDNA. This suggested to researchers that there was this rogue human group (some [not I] might say ‘species’) running around Eurasia around the time of the Upper Paleolithic.



Well now they’ve sequenced the nuclear genome of one of a Denisova denizen. The picture painted is that a Denisova-Neandertal ‘lineage’ split off from that of modern humans some time in the distant past, then the Denisovans split from Neandertals some time later. Most interesting, modern-day Melanesians seem to derive about 4% of their genes from this ‘archaic’ Denisovan lineage, whereas this archaic genetic baggage isn’t present in other modern human populations.


AMAZING! Think back to the draft of the Neandertal nuclear genome, also published earlier this year. Green and colleagues (2010) reported that the Neandertal nuclear genome revealed that Neandertals contributed up to 4% of the genomes of modern-day non-Africans. Now, the Denisova genome shows that a different and more specific group of modern humans (Melanesians) appears to uniquely share a different set of nuclear genes from an ‘extinct’ human group.


But if they contributed their genes to modern people, are they really extinct? Of course not! I’m admittedly not a geneticist, but I think what we’re seeing here are the genetic signatures of a single, ancient structured population of modern humans. That is to say, all modern humans derive different amounts of their genes from various ancient subpopulations of ‘archaic’ humans (for ‘archaic,’ think ‘people that lived a long time ago’). There was just little enough contact between these populations for them to have diverged slightly from one another, but still enough contact for them all to have contributed different parts and amounts of genes to people today.


It is weird, then, to see the ancient DNA geneticist Svante Pääbo (out of whose lab this ancient genetic work is done) say this to BBC News:

“It is fascinating to see direct evidence that these archaic species did exist (alongside us) and it’s only for the last few tens of thousands of years that is unique in our history that we are alone on this planet and we have no close relatives with us anymore.”

Why are these ‘archaic species…alongside us”? The fact that these groups were mixing means that they are a single species – the ability (and propensity) to interbreed is the standard definition of ‘species’ used in modern biology.


So contrary to Pääbo’s quote, I’d say we do have close relatives with us, it’s just that modern humans are much more closely to one another related than ancient human populations were to one another. Probably there is more contact between modern human populations, beginning a few tens of thousands of years ago, because population sizes explode to the some 7 billion people we have on earth today. This greater contact means less chance for populations to diverge from one another.


The take-home: We all have multiple ancestors, from various times and places. For more comprehensive and better-informed coverage, check out John Hawks’s post on the topic.
ResearchBlogging.org
References
Green, R., Krause, J., Briggs, A., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M., Hansen, N., Durand, E., Malaspinas, A., Jensen, J., Marques-Bonet, T., Alkan, C., Prufer, K., Meyer, M., Burbano, H., Good, J., Schultz, R., Aximu-Petri, A., Butthof, A., Hober, B., Hoffner, B., Siegemund, M., Weihmann, A., Nusbaum, C., Lander, E., Russ, C., Novod, N., Affourtit, J., Egholm, M., Verna, C., Rudan, P., Brajkovic, D., Kucan, Z., Gusic, I., Doronichev, V., Golovanova, L., Lalueza-Fox, C., de la Rasilla, M., Fortea, J., Rosas, A., Schmitz, R., Johnson, P., Eichler, E., Falush, D., Birney, E., Mullikin, J., Slatkin, M., Nielsen, R., Kelso, J., Lachmann, M., Reich, D., & Paabo, S. (2010). A Draft Sequence of the Neandertal Genome Science, 328 (5979), 710-722 DOI: 10.1126/science.1188021


Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, Viola B, Briggs AW, Stenzel U, Johnson PL, Maricic T, Good JM, Marques-Bonet T, Alkan C, Fu Q, Mallick S, Li H, Meyer M, Eichler EE, Stoneking M, Richards M, Talamo S, Shunkov MV, Derevianko AP, Hublin JJ, Kelso J, Slatkin M, & Pääbo S (2010). Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature, 468 (7327), 1053-60 PMID: 21179161

Genes and culture in animals

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Recent UM Ph.D. Kevin Langergraber and others (including UM primatologist John Mitani; 2010) recently reported on a high correlation between genetic relatedness and ‘cultural’ behavioral repertoire in wild chimpanzees.

Chimpanzees, and other animals, have been observed to display behaviors that appear ‘cultural,’ since the behaviors are variously a) learned from other individuals, b) specific to certain chimp populations, and/or c) not recognizably adaptive. Such behavioral variants include, for example, how hands are clasped during grooming (photo from Whiten, 2005), or whether/how insects are acquired.

Researchers have debated whether these behavioral variants actually represent culture, in the sense that humans have culture. This itself is tough because anthropologists have had a helluva time defining what ‘culture’ is simply for humans, let alone animals. I’m a bit anthropocentric myself, and I’m wont to view culture as something uniquely human, the adaptation (or set of adaptations) that has essentially shaped our evolution for over a million (2 million?) years.
Anyway, back to Pan, Langergraber and colleagues set out to test whether genetic variation may help explain some of the behavioral variation between different chimp populations. Lo and behold! there was a significant correlation between groups’ genetic dissimilarity and behavioral dissimilarity. This isn’t at all to say the authors have found the genetic basis for cultural behaviors, but rather that some genetic variation may underlie some behavioral variation we see in chimpanzees. Indeed, the authors note that the mtDNA used in the study doesn’t ‘code for’ any of the putatively cultural behaviors; it’s a proxy for genetic relatedness. However, there was no clear pattern of which types of behaviors (e.g. grooming- vs. feeding-related) correlate with genetic relatedness.
The results are a bit tough to interpret. The authors state that the finding of a correlation does not mean that many chimp behaviors analyzed are not cultural. But it doesn’t necessarily mean that the behaviors are cultural, either. This gets really tricky for a number of reasons.
First, identifying “the” or “a” genetic basis for phenotypes is difficult, and it’s especially difficult for complex phenotypes like behaviors (in general, if you ever hear about a “gene for” some behavior, immediately disbelieve it). The analysis uses an allegedly neutral DNA marker, that admittedly does not ‘code for’ any of the behaviors in question. All the DNA can do here is attempt to indicate relatedness among groups. To say that “genetic differences cannot be excluded as playing a major role” in patterning behavioral variation (p. 7), basically means that some unexamined genetic region may be patterned among populations the same way as the mtDNA marker, and might be responsible for specific, fine-tuned, non-adaptive aspects of their behavior. The authors discount the possibility of the link being due to kin teaching behaviors to kin, but I would suppose a higher resolution (like looking at relatedness and behavior between individuals rather than groups) would put that matter to rest.
Next, how much of a correlation is biologically (and here culturally?) meaningful? In various permutations of their analysis, the correlations between the behavioral and genetic dissimilarity matrices ranged from r = 0.37 – 0.52, most of which were significant. “Significant” here means that the correlation coefficients, r, are different enough from zero – there isn’t no relationship between the variables (I mean to say the double negative). Put another way, we can square the r coefficients to get the ‘amount of variance explained’: 13.7 – 27.0% of the behavioral dissimilarity can be ‘explained’ by genetic dissimilarity. What if the correlation coefficients had been higher – would this be better evidence for some genetic basis for chimp behavioral variants? I love correlation as much as the next guy, but aside from significance level, variation in linearity is not always completely understandable.
So, regardless of the results of the analysis, do apes (or other non-human animals) have culture? An interesting conundrum is that when people describe the subtle variants of behavior as cultural, they’re assuming the variation itself is non-adaptive, while the grand behavior itself purportedly is. Can things that are readily adaptive (ecological explanation) not also be cultural? Moreover, how widespread in a population must a behavioral variant be to be cultural? How many variants on a theme are permissible within a population? Questions like these are why I tend to shy away from the topic of culture, in humans and animals.
References
Langergraber K, Boesch C, Inoue E, Inoue-Murayama M, Mitani JC, Nishida T, et al. Genetic and ‘cultural’ similarity in wild chimpanzees. Proc R Soc B in press. Proc. R. Soc. B doi:10.1098/rspb.2010.1112 (2010)
Whiten A. 2005. The second inheritance system of chimpanzees and humans. Nature 437: 52-55.

Neandertal Nuclear Genome: Multiregional Evolution is the new Out of Africa

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Green and colleagues announced the Neandertal nuclear genome in tomorrow’s issue of the journal Science. Hitherto only complete mitochondrial DNA (mtDNA) genomes had been recovered. These are only inherited maternally, and the genetic differences between the Neandertal mtDNA and that of modern humans seemed to suggest that Neandertals and humans didn’t mix, that is that they were replaced by “anatomically modern humans” (whatever that phrase means). mtDNA is special as far as genetic stuff goes – only inherited maternally, so only tells about one strain out of a slew of ancestors; doesn’t recombine; as a result, selection acting on a part results on selection of the entire mitochondrial genome; oh and it’s certainly not selectively neutral.
So should we have been wary when it was suggested by mtDNA that neandertals and humans were separate species (recall the issue was even crazier with the Denisova mtDNA specimen…)?
YES – HUMANS AND NEANDERTALS EXCHANGED GENES (but just Eurasian humans…)

This is a big deal, because for the past several decades researchers have debated the nature of modern human origins. On morphological and shaky mtDNA evidence, several researchers have argued that modern humans emerged from a small African population, which then spread throughout the world between 100-200 thousand years ago and replaced all other ‘archaic’ human populations. Intuitively this doesn’t make sense, and today’s neandertal announcement renders the Out of Africa with Replacement model for human origins absolutely untenable.
So, were Neandertals and (even then-modern) humans the same species? Yes! If Neandertals were a different species, we would expect all humans to be equally genetically divergent from neandertals. But this is not what Green and colleagues found. Rather, the genomes of a French person, a Chinese person, and a Papua New Guinean were actually more similar to the Neandertal genomes than the two African human representatives were to the Neandertals. Such disparate divergences mean we’re dealing with genetic variation within a species, rather than between species.
In fact, the authors estimate that about 1-4% of modern, non-African genomes are derived from Neandertals. Plagnol and Wall (2006) estimated around 5% of human genes come from ‘archaic’ humans, so it is good to see corroborating evidence from two sources. It is interesting, however, that earlier candidates for introgression from archaics, such as the microcephalin haplogroup D, do not appear to have come from Neandertals (maybe another archaic population, then?).
The authors were also able to use these neandertal and modern human genomes to estimate regions of the human genome that have been under recent and accelerated evolution, including:
  • SPAG17 is associated with sperm motility – is this evidence for sperm competition and recent sexual selection?
  • Regions in which, among modern humans, mutations are associated with social-cognitive diseases like schizophrenia and autism
  • RUNX2, again where misexpression in humans is associated with dysgenesis of frontal bone (forehead), shoulder and rib-cage shape morphology
Interesting…
I think the only things I would have loved to have seen in this study are simple logistical issues, things that are probably simply not practical at the moment because of technological constraints. First, I’d love to see a much larger set of modern human reference genomes. The study included only 2 human nuclear genomes from sub-Saharan Africa, 1 from Europe, 1 from China and 1 from Papua New Guinea. Yes, this samples variation from all over the world, but it’s 5 out of nearly 7 billion genomes out there today. At the moment, however, it’s just not that easy to acquire and handle genomic data for many individuals.
Second, I’d like to see nuclear genome comparisons using Upper Paleolithic modern humans – ‘modern human’ contemporaries of Neandertals. The Denisova mtDNA was surprising because, at some 40 ka, its genome was about twice as different from modern humans as the neandertal mtDNA sequences were. Just what kind of genetic diversity are we looking at in ancient (anatomically both ‘archaic’ and ‘modern’) humans?
Green and colleagues should be lauded because of how meticulously they went about this project. They took major pains to circumvent issues of contamination, they maximized the DNA they could obtain in spite of preservation issues, they came up with some clever tests. And their results are really interesting.
References
Green RE et al. 2010. A draft sequence of the Neandertal genome. Science 328: 710 – 722.
Plagnol V and Wall JD. 2006. Possible Ancestral Structure in Human Populations. PLoS Genetics 2(7): e105

I, or someone, have drawn a brown, orange, and blue Gwenhidwy

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You’re probably thinking, “I thought zacharoo was dead,” because I’ve been completely MIA for the past few weeks. My apologies, but I was trying to wrap up this past semester, the terminus of my first year in grad school. And I must say I think I did a pretty good job, not to toot my own horn. This is as good a time as any to ask, “What the eff have I learned this year?”

1. Milford is awesome. Probably the past few decades have shown this, but I’ve only known the guy for less than a year. Given my more ‘arts’ educational background, Milford (and the Big Chief and the rest of the bios) have taught me how to do ‘science,’ formulating and testing a hypothesis. Though I’m certainly no Chung-I Wu, my mentors and colleagues have certainly gotten me started. Also, I was a bit unhappy with Milford last semester for pushing me and my peers to take a heavy course load. But I must say it was worth it, I’ve learned a lot this past year, and if I’d taken another (i.e. the non-bio) way I would not have learned nearly as much. He can also improvise a wicked country-twangy song (“I wish I grew up on a pig farm”). Great advisor, great man.

2. Steer clear of the hobbit. That situation is messier than the van-ride back from DC. I talked about LB 1 (the hobbit skull) in a few posts earlier this year. It’s clearly not a cretin, and at the AAPA meetings in Columbus a few weeks ago, Dean Falk defensively countered the Laron Syndrome hypothesis. Bill Jungers reported at the meetings that the foot of LB 1 was not that of a runner (I forget the specifics, but it was missing one or both of the plantar arches). It’s overall cranial shape based on various measurements show it has striking affinity with Homo habilis (in a broad sense) <!–[if supportFields]> ADDIN EN.CITE Gordon200810310317Gordon, Adam D.Nevell, LisaWood, BernardThe Homo floresiensis cranium (LB1): Size, scaling, and early Homo affinitiesProceedings of the National Academy of SciencesProc Nat Acad SciProc Nat Acad Sci07100411052008March 20, 2008http://www.pnas.org/cgi/content/abstract/0710041105v1 10.1073/pnas.0710041105<![endif]–>(Gordon et al. 2008)<!–[if supportFields]><![endif]–>. Chief, her husband Adam, Pappano, and I looked at UM’s collection of modern human ‘microcephalics’ (there are myriad ways to be microcephalic), and found that LB 1 is still more similar to the habilines (cf. Gordon et al 2008). This really suggests to me that maybe some early Homo or Australopithecus species made it out of Africa to Flores early in human prehistory; however, I don’t think we can say yet whether it’s a real case of insular dwarfing in a hominin or pathology or what. Still very messy.

3. Molding and casting is neat but difficult. One of the projects Milford got me started on a cranial reconstruction. Sounded simple enough at first, but it has required me to make molds and casts of the individual cranial bones: the two temporals, occipital and the paired parietals were not too difficult, but the face is really giving me grief. It was also difficult fitting my busy schedule to Bill Sanders’s lab schedule. So, long story short, I didn’t finish the project (should be done before June . . .), but Bill has taught me a ton about molding and casting, as well as proffered his wisdom. It has also reinforced my desire to be a paleontologist. Cool beans.

4. Genetics sucks. For decades now, paleoanthropology has come to be not just about fossils, but also about molecules. Today, genetic studies are incredibly influential in studies of human evolution, i.e. supporting models of migration and introgression. But I took a course this past semester in the department of Ecology and Evolutionary Biology, and it seems to me that molecules are not really any less unequivocal than fossils. Really genetics is all comparing predictions of models with various parameters (i.e. effective population size, population expansion, etc.) with actual empirical data, and it’s all about probability. So you can say something like, “There is a high probability of seeing this type of data given that type of hypothesis/model.” But different sometimes data have the same probability given different parameters. So genetics can tell a lot, but you have to take what they say with a gram of coke, I mean granary of salt. And all the nucleotides in the world probably won’t help resolve robust australopithecine phylogeny.

Now I’m tired, so I’ll stop there for now. I’ll post more pearls (of wisdom) I learned this semester as I recall them. So that’s where I’ve been o’er the past few somethings. Weeks. Oh, and I just received a possible job offer working with crash-test dummies (or something, I’m not exactly sure) with the UM Transportation Research Institute, hopefully that works out.

Reference

<!–[if supportFields]> ADDIN EN.REFLIST <![endif]–>Gordon AD, Nevell L, and Wood B. 2008. The Homo floresiensis cranium (LB1): Size, scaling, and early Homo affinities. Proceedings of the National Academy of Sciences:0710041105.