Pages

Monday, January 30, 2012

Taking back Epigenetics

If I'm good at anything, it's looking into one topic and then getting distracted by something else during my search. In a recent case, I was scouring the literature on growth and life history. One ribald thing led to another, and next thing I know I've stumbled upon Gunter Wagner's recent review of the book Epigenetics: Linking Genotype and Phenotype in Development and Evolution. WTF is epigenetics, you ask? That's actually a pretty good question (see here). In the past several years, the term has most often been associated with the causes/effects of structural modifications to chromatin (the DNA-containing stuff that makes up chromosomes). For sure, coincident with Wagner's review, a paper in last week's Nature Reviews Genetics defines epigenetics as "the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence." (Feil and Fraga 2012).

This is an extremely narrow focus for a term that was originally meant to be about basically everything besides genes that contribute to an organism's phenotype (this idea was developed by the great, rather underrated, 20th century biologist Conrad Waddington). Lotsa epigenetics research by the narrow definition (i.e. modifications to histones and chromatin) focuses on how cells - not organisms - retain their identity/function (or, phenotype). Epigenetics in the narrow sense are important determinants of an organism's phenotype, but these alone are insufficient to understand how and why organisms' become the way they are. Yes, the narrow definition leaves room for environmental influences on gene expression (though "environment" could refer to the state of affairs within a cell or an organism, in addition to the outside world). But it nevertheless imparts agency solely to genomes in affecting an organism becomes.

And this is what the aforesaid book and review are about. Wagner asks, "what would be lost if the original perspective of epigentics [as defined by Waddington] was lost to science?" This is important because an organism is not simply a robotic readout of its genes, but people cannot seem to shake this centuries-old biological determinism.

Is that a homunculus
in your [sperm's]
pocket?
In the early days of 'modern' (or let's say 'recent') biology, there was a popular idea of "Preformationism," that animals grew from these pre-formed miniature versions of themselves (homunculi) in germ cells. It did not take long for this idea to be quashed, but the underlying idea persisted. Wagner recounts, "With the rise of genetics during the 20th century, however, a new form of quasi-preformism arose, basically replacing the old homunculus with the genome, whereas the developmental process creating the phenotype was put in a black box" (emphasis mine). [See Gilbert et al. (1996) for a nice historical overview describing how the rise of population genetics in the early 20th century left embryology and developmental biology by the wayside of the Modern Evolutionary Synthesis]

This latent desire to essentialize biology to some singular determinant (be it an homunculus or a gene) is something people just can't get away from. Srsly, there's a persistent sentiment in biology that Real Science is only the high-profile, lab-coated work in genetics. Along these lines, even I adopted the recently popular narrow view of "epigenetics" a while back when I dated a woman who worked at an epigenetics lab, in hindsight probably so I would sound more like a capital-S Scientist (below).

Hipster scientist. H3S10 phosphorylation correlates with 
decreased levels of heterochromatin, possibly regulating
chromosome condensation (Chenet al 2008). Image: bit.ly/zEfPaq
Of course, genes code for how a cell should behave, but we have this tendency to want to extrapolate from the cell to the organism, and this is where developmental biology becomes a critical link. And this is what the new Epigenetics book is about (so far as I can tell, I haven't yet had a chance to read it all).

It's abundantly clear that phenotypes arise out of an inextricably complex series of interactions - between genes, proteins, cells, tissues, environments, etc. These interactions do not occur solely at the genetic (or narrow-sense epigenetic) level. Developmental biology helps 'connect the dots' between genes and morphology, but cannot do so by focusing solely on genes and chromatin.

ResearchBlogging.org
References
Chen, E., Zhang, K., Nicolas, E., Cam, H., Zofall, M., & Grewal, S. (2008). Cell cycle control of centromeric repeat transcription and heterochromatin assembly. Nature, 451 (7179), 734-737 DOI: 10.1038/nature06561

Feil, R., & Fraga, M. (2012). Epigenetics and the environment: emerging patterns and implications. Nature Reviews Genetics DOI: 10.1038/nrg3142

Gilbert, S. (1996). Resynthesizing Evolutionary and Developmental Biology. Developmental Biology, 173 (2), 357-372 DOI: 10.1006/dbio.1996.0032

Hallgrímsson B and Hall BK, eds. 2011. Epigenetics: Linking Genotype and Phenotype in Development and Evolution. Berkeley: University of California Press.

Wagner, G. (2011). Epigenetics in all its beauty Trends in Ecology & Evolution DOI: 10.1016/j.tree.2011.09.003

Monday, January 23, 2012

A little reassurance


I was putting together a lab lesson for this week, focusing on the skeletal differences between living apes and Old World monkeys, when I'd noticed the distal humerus of this gorilla (Gorilla gorilla, not the most "scientific-sounding Latin names," right?). Looks kinda like a thumbs-up, I thought. It seemed to say, "Keep up the good work, kid!" And that's when I knew it was time to get some sleep.

Saturday, January 21, 2012

Historical contingency and an herbivorous calamity

This post was chosen as an Editor's Selection for ResearchBlogging.org
A while ago I asked, "What the hell was Australopithecus boisei doing?" To recap: there's this weird side branch of human evolution that was dubbed "Australopithecus boisei" and lived in Eastern Africa from around 2.3 - 1.4 million years ago. They lived right alongside our ancestors, early Homo. If you think human diversity is remarkable today, you'd be totally blown away by the diversity of the early Pleistocene. Since 1959 when A. boisei (then Zinjanthropus boisei) was first discovered, people noticed its massive molar and premolar teeth, thick and powerful jaws, and muscle markings indicative of diabolical chewing power. 'Probably subsisted on a diet of low-quality, hard to chew foods,' people reasoned.

But a few years ago, this picture changed: evidence from toothwear and the chemical composition of teeth suggested A. boisei was actually eating grass or sedges (see the referred post or a nice recent review by Julia Lee-Thorp for more info). Such a diet is totally at odds with what people had hypothesized based on the size of the chewing muscles and teeth.

Colobus molars (image: http://bit.ly/xefm6t)
I was discussing this last point with a colleague the other day, who could not believe A. boisei ate grasses or the like: Many animals known to eat grass or leaves tend have molars with high crowns with slicing edges for shearing apart a mouthful of vegetation (left), but A. boisei molars are large and low-cusped, becoming fairly flat with wear (below).


KNM-ER 15930 (Leakey & Walker 1988, Figure 8)

But, it occurred to me, maybe high-crowned, shearing molars simply were not an 'option' in the evolution of Australopithecus boisei. Natural selection is a powerful force of evolution, but it is limited because it can work only with existing variation: it does the best it can with what it's got. The earliest surefire hominids*, Australopithecus anamensis and afarensis, certainly did not have 'cresty' molars with pointy cusps, and neither did many late Miocene apes, for that matter. Rather, the ancestors of A. boisei had fairly low bulbous molar cusps, and that's some serious evolutionary baggage for a hominid hoping to corner the grass and sedge market.

So we can draw up the following hypothesis for the evolution of A. boisei: as the early members of the species moved into a niche of eating grass/sedges, rather than evolve cresty teeth, they increased the size and enamel thickness of their ancestors' molars to better-withstand their diet. Perhaps this was the 'easiest' solution to adapting teeth to a crappy diet (maybe some developmental constraint?). Or perhaps there's another, yet unidentified food responsible for the species' curiously high-C4 diet ... who knows? Nota bene: this isn't necessarily what I think happened, it's just a hypothesis consistent with current evidence about A. boisei's anatomy and diet.

If Life on Earth has taught us anything, it's that there are many ways to do the same thing. What's more, evolution is highly constrained by pre-existing biology and historical circumstance. Australopithecus boisei may have been 'a victim of its times,' forced into an herbivorous niche for which it was ill-equipped.

READ MORE!
Leakey RE, & Walker A (1988). New Australopithecus boisei specimens from east and west Lake Turkana, Kenya. American Journal of Physical Anthropology, 76 (1), 1-24 PMID: 3136654

Lee-Thorp, J. (2011). The demise of "Nutcracker Man" Proceedings of the National Academy of Sciences, 108 (23), 9319-9320 DOI: 10.1073/pnas.1105808108

* I only mention australopithecines because I'm still on the fence about the hominid status of Ardipithecus, and not convinced by Orrorin or Sahelanthropus.

Wednesday, January 4, 2012

miRNA special reprint in Nature

A while ago I had a small post about RNA interference (RNAi), linking to a really awesome and educational animation and slideshow on the topic. Again, RNAi refers to gene regulation by very small strands of RNA. There are a number of types of RNA in your cells, and a several of these are involved in RNAi: in the last post I cursorily mentioned piwi-interacting RNAs (piRNA), small interfering (siRNA) and long intergenic non-coding (lincRNA).

One type I neglected to mention is "micro" (miRNA), and this is the one about which the journal Nature has a special on-line issue. miRNA, like other types in RNAi, binds to messenger RNA in cells to prevent gene translation. The special issue of Nature focuses on miRNA in various diseases involving tumors and skeletal abnormalities, and so far as I can tell, it's completely free to all!

What really caught my eye about this issue is its highly interactive medium, produced by some company called zmags. This "zmag" (I guess you'd call it?) has been rendered so that you view and leaf through actual magazine-like pages in your browser. I've got a 1+ yr old Macbook and the 2-finger zoom on the trackpad also works within the browser. Want to read and mark up some of it in your preferred program? Well you can save selected pages from the issue as a pdf, giving you flexibility in what content you download (though I did have some issues with this). A while ago I noticed Nature also used a somewhat interactive in-browser, pdf-viewing app called Readcube, though I admit I haven't really toyed with that program.

It's a bit challenging but also interesting to follow the possible obsolescence of the (literally) printed word. Amazon's Kindle and other e-book platforms have all but buried the expensive, clunky hardcover tome. Academic publishers like Springer offer not only articles but also whole book chapters as pdfs available online (though they tend to require some type of university or other affiliation), and major newspapers offer most of their content on their websites.

ResearchBlogging.orgOn this topic, Carl Zimmer had a neat piece in Nature a few weeks ago about the "rise of the e-book." He raises some excellent points regarding the pros and cons of e-books, some which I think could be extended to digital media more generally. I for one am like millions of others, relying on my handy computer and the internet for nearly all information I need to be a fully-functioning student, teacher and member of society. Still, as Zimmer points out at the end of his article, the permanence of e-books and the like is uncertain. I mean, what to do if we're hit by another devastating Y2k?

Read on
Nature special issue here

Zimmer, C. (2011). Technology: Rise of the e-book Nature, 480 (7378), 451-452 DOI: 10.1038/480451a

Sunday, January 1, 2012

Evo-devo of the human shoulder?

It's a new year, and while my mind should be marred by a hangover, instead all I can think about are fossils and scapulas.


A pretty cool study was published online in the Journal of Human Evolution last week, and I've finally gotten to peruse it. Fabio Di Vincenzo and colleagues analyzed the shape of the outline of the glenoid fossa on the scapula (not to be confused with the glenoid on your skull), from Australopithecus africanus to present day humans. The glenoid fossa is essentially the socket in the ball-and-socket joint of your shoulder. The authors found that there is pretty much a single trend of glenoid shape change from Australopithecus through the evolution of the genus Homo: from the fairly narrow joint in Australopithecus africanus and A. sediba, to the relatively wide joint in recent humans. The overall size and shape of the joint influences/reflects shoulder mobility, so presumably this shape change hints that more front-to-back arm motions became more important through the course of human evolution (authors suggest throwing in humans from the Late Pleistocene onward).


The finding of a single predominant trend in glenoid shape evolution is pretty interesting. On top of that, the authors add an ‘evo-devo’ twist by comparing species’ average "shapes" (first principle component scores, on the y-axis in the figure at right) with their estimated ages at skeletal maturity (which appears scaled to the modern human value, on the x-axis). Though it’s not an ideal dataset for running a linear regression, the figure at right shows that there appears to be a fairly linear relationship across human evolution, such that groups with an older age at skeletal maturity tend to have a more rounded (modern human-like) glenoid fossa (note that the individuals in the analysis were all adults). Overall size does not contribute to shape variation among these glenoids.


This work raises two issues, and ultimately leads to a testable evo-devo hypothesis. The first issue is to what extent we can trust their estimates of age at skeletal maturity. These estimates were allegedly taken from a chapter by Helmut Hemmer (2007) in the prohibitively expensive Handbook of Paleoanthropology. Cursorily glancing at this chapter, I can't find age at skeletal maturation estimated for any hominids. It is possible that in my skimming I missed the estimates, or alternatively that Di Vincenzo and colleagues misinterpreted another variable as skeletal development. Either way, these estimates would still need to be taken with a grain of salt, given that it is almost impossible to know the true age at death of a fossil (but see Antoine et al. 2008), especially if there are no associated cranio-dental elements.


That said, it is perfectly reasonable to suppose that the age at skeletal maturation has increased over the course of human evolution; life-span increased through human evolution, and so all else being equal (which it almost certainly isn't) we could expect that maturation would occur later over time, too. So this leads to a second issue: given the “evo-devo change” the authors hypothesize, what is the evo-devo mechanism? That is, how was development modified to effect the evolutionary changes we see in the hominid scapula? Because they found adult glenoid shape correlates with estimated age at skeletal maturity, this leads to the hypothesis that postnatal skeletal growth accounts for the shape difference. Indeed, they state:
“If functional and static allometric influences are unlikely, we…interpret the trend…as reflecting growth and developmental factors. A major, albeit gradual, trend of ontogenetic heterochrony occurred in the evolution of the genus Homo... and thus differences within and between taxa in overall growth rates may have produced the pattern of variation between samples, as well as the overall temporal trend observed. The regression of life history variables [they only looked at 1]... with PCA [principle components analysis] scores supports this ‘ontogenetic’ hypothesis.”
The authors suggest that humans’ slower growth rates but longer growth period “led to longer periods of bone deposition along the inferior-lateral edge of the [glenoid fossa]”  The heterochronic process they suggest is “peramorphosis” – the descendant reaches a shape that is ‘beyond’ that of the ancestor.
The figure above is from a seminal "heterochrony" paper by Pere Alberch and colleagues (1979), portraying how peramorphosis can occur. In each, the y-axis represents shape and the x-axis is age. A the descendant's peramorphic shape ("Ya") could result from accelerated growth (left graph) or from an extension of growth to later ages than in the ancestor (right graph).


And so this leads to a testable hypothesis. Di Vincenzo and colleagues cite (dental) evidence that humans' overall body growth rates are slower than earlier hominids', undermining the hypothesis that acceleration is responsible for humans' glenoid peramorphosis. Rather, they hypothesize that humans' slower growth rates coupled with a longer period of skeletal development, to result in a relatively wider glenoid, due to increased development of the secondary growth centers (e.g. the graph at right, above). This developmental scenario predicts that subadult human glenoids should resemble earlier hominid adults', that "ontogeny recapitulates phylogeny" as far as glenoid shape is concerned. Analyzing glenoid growth can even be extended to include fossils - the >3 million year old human ancestor Australopithecus afarensis has glenoids preserved for an infant (DIK-VP-1; Alemseged et al. 2006) and 2 adults (AL 288 "Lucy" and KSD-VP-1; Johanson et al. 1982, Haile-Selassie et al. 2010). An alternate hypothesis is that species' distinct glenoid shapes are established early during life (i.e. in utero), and/or that no simple heterochronic process is involved.


ResearchBlogging.orgDi Vincenzo's and colleagues' study points to the importance of development in understanding human evolution, and their hypothesized "evo-devo change" in glenoid shape is ripe for testing.


References
Pere Alberch, Stephen Jay Gould, George F. Oster, & David B. Wake (1979). Size and shape in ontogeny and phylogeny Paleobiology, 5 (3), 296-317


Alemseged, Z., Spoor, F., Kimbel, W., Bobe, R., Geraads, D., Reed, D., & Wynn, J. (2006). A juvenile early hominin skeleton from Dikika, Ethiopia Nature, 443 (7109), 296-301 DOI: 10.1038/nature05047


Antoine, D., Hillson, S., & Dean, M. (2009). The developmental clock of dental enamel: a test for the periodicity of prism cross-striations in modern humans and an evaluation of the most likely sources of error in histological studies of this kind Journal of Anatomy, 214 (1), 45-55 DOI: 10.1111/j.1469-7580.2008.01010.x


Di Vincenzo, F., Churchill, S., & Manzi, G. (2011). The Vindija Neanderthal scapular glenoid fossa: Comparative shape analysis suggests evo-devo changes among Neanderthals Journal of Human Evolution DOI: 10.1016/j.jhevol.2011.11.010


Haile-Selassie, Y., Latimer, B., Alene, M., Deino, A., Gibert, L., Melillo, S., Saylor, B., Scott, G., & Lovejoy, C. (2010). An early Australopithecus afarensis postcranium from Woranso-Mille, Ethiopia Proceedings of the National Academy of Sciences, 107 (27), 12121-12126 DOI: 10.1073/pnas.1004527107


Hemmer, Helmut (2007). Estimation of Basic Life History Data of Fossil Hominoids Handbook of Paleoanthropology, 587-619 DOI: 10.1007/978-3-540-33761-4_19


Johanson, D., Lovejoy, C., Kimbel, W., White, T., Ward, S., Bush, M., Latimer, B., & Coppens, Y. (1982). Morphology of the Pliocene partial hominid skeleton (A.L. 288-1) from the Hadar formation, Ethiopia American Journal of Physical Anthropology, 57, 403-451 DOI: 10.1002/ajpa.1330570403