(Of fins, genes, fossils and the nature of evidence)
Behold the lengthy going-on about limbs, developmental genetics and semi-philosophical stuff that I promised! I mentioned that this was long in the making. Ironically, that means I’m not sure I managed to make it coherent… Then again, my blog subtitle does warn you about certain “meanderings” 😉
I previously mentioned that limbs kind of brought me to evo-devo. I haven’t closely followed the subject since, but a recent paper (Schneider et al., 2011) brought it back to my attention. Aside from the nostalgia, the evolution of limbs is also a perfect excuse for me to ruminate on some of the issues I consider important in evo-devo – such as the meaning of evidence, the role of “model organisms” and the nature of homology and novelty. (Some of this I touched on in my treehopper post)
I love developmental genetics. Davis et al. (2007), which through the blurred glasses of hindsight I’ll call the paper that made me an evo-devo nerd, is a genetic study. Genes are really exciting for us evolutionists because they obey different rules from the traits they control. Especially for regulatory genes – those that affect the activity of other genes –, gene sequence doesn’t correspond to the appearance of the organism in any straightforward way. The same circuitry of regulatory genes can also control the development of quite different structures, because most of the actual work is done by their target genes. Therefore, genes can often preserve connections we can no longer see in higher-level traits. (My favourite combination of evidence is genes plus fossils, but bear with me a little…)
The gist of Davis et al. (2007) is as follows. Hands and feet (collectively known as the autopod) are unique to tetrapods, or vertebrates with legs. There’s a special pattern of Hox gene activity that controls autopod formation. This pattern was missing from the fish that had been examined at the time. However, those fish are quite different from the distant ancestors they shared with tetrapods. There are living fish whose fin skeletons include bits that might correspond to digits, and there are many fossil examples. These include, as it later turned out, not just the iconic fishapod Tiktaalik, but also its slightly less tetrapod-like relative Panderichthys (Boisvert et al., 2008). Hence the question: did common lab animals like zebrafish lose the bones and the genetic circuitry, and did the bones of the autopod evolve from particular bones of the ancestral fin, or did tetrapods invent something new?
The answer is almost certainly the former, Davis et al. (2007) tell us after they find the tetrapod kind of Hox gene expression in the fins of a comparatively “primitive” ray-finned fish (Ray-fins are one of the two main groups of bony fishes. The zebrafish is a ray-fin, as are other familiar fish like cod and tuna. The other group – lobe-fins – include lungfish, coelacanths and tetrapods themselves). Around the same time, other teams found similar patterns in lungfish (Johanson et al., 2007), which are probably the closest living relatives of tetrapods, and sharks (Freitas et al., 2007), which are only distantly related to any of the creatures mentioned above.
Schneider et al. (2011), which caused this post, found that some DNA elements that regulate the Hox genes in the autopod are shared by tetrapods, ray-fins and sharks (ergo, probably all living vertebrates with fins or limbs). Together with the evidence from fossil and modern skeletons, this suggests that the digits of tetrapods evolved from pre-existing fin bones by tweaking an ancient genetic program. Fins and limbs really are variations on a single ancient theme. (Illustration of “fishapod” fins and early tetrapod limbs below is by Dennis C Murphy, from Devonian Times)
It is at this conclusion that we come to the stuff Hox gene expression can’t tell us. Knowing that radial bones (or cartilages, as the case may be) in fins and digits in limbs are “really the same thing” in some way is one thing. But radials and digits are not that similar, and neither is a shark’s fin and a newt’s leg. Maybe you’re interested in how one became the other, how fins suited to balancing and manoeuvring in water became limbs suited to plodding along on land. The autopod-like Hox pattern doesn’t say, since it’s basically the same in appendages that look very different, a perfect example of what I said about regulatory genes a few paragraphs back. Clearly, Hox genes define a distinct part of the fin or limb, but they don’t give detailed instructions on how to flesh it out. The details depend on the genes under Hox control.
Now, fins and limbs are relatively easy, because we have a really quite awesome fossil record of their history (and also, some cool computer models :D). But the same lessons we can learn from their example apply equally to countless other cases where the fossil record is silent. Shared expression patterns of “master” genes and genetic pathways are often used to infer things about ancestors that aren’t known from fossils at all (De Robertis, 2008 is a nice review of such pathways). How far can we take such inferences? What does the fact that arthropods, vertebrates and segmented worms all seem to use some of the same genetic pathways to generate their bodies from repeating units (e.g. Stollewerk et al., 2003; Pueyo et al., 2008; Rivera and Weisblat, 2009)? Was their common ancestor as obviously segmented as an earthworm, did it just have a few repeated body parts like a chiton, or maybe nothing more than the basic ladder-like nervous system* of bilaterian animals? Or perhaps even less?
[*Photo of the nervous system of a planarian flatworm stained with a fluorescent dye, by the Agata group.]
The fossil record of early animal evolution (or rather, the lack of it) argues that this common ancestor was relatively small and simple (Erwin and Davidson, 2002). We know that quite different structures can be underpinned by the same “master” genes. Given this, can we really say anything meaningful about such long-extinct creatures? Well, we certainly can. They probably had the genetic circuitry their descendants share today. But what does that say about their body plans?
The answer may not be too far from “fuck all”. That’s why I chose a quote from Tabin et al. (1999) for the title of this post. I couldn’t agree more when they write, “developmental genetics only tells us what characters might have been possible”. I love finding out where we and the other creatures with whom we share this planet came from. That’s why I’m in this business. But there is only so much that any given type of evidence can tell us. And this is why I think the fossil record is so important. Like Erwin and Davidson (2002) argue, it can help us distinguish between “might have beens” in sometimes surprising ways.
All of this puts the whole concept of homology into a slightly unsettling new perspective. Homologues (often spelled “homologs” nowadays) are supposed to be traits (genes, organs, behaviours etc.) that are derived from the same ancestral trait. The original concept of homology was defined for whole organs/body parts. Now, what do we do with organs that are made by the same genetic networks? Some of them show obvious historical continuity with the organs of other organisms. A bird’s wing is clearly homologous to my arm, on probably every level imaginable. They are connected by similar position on the body, similar basic structure, similar development and developmental genetics, and a rich fossil record. But that absolutely need not be the case.
Some butterflies use the same genetic circuitry to put eyespots on their wings that insects in general use to subdivide their wings into different regions (Keys et al., 1999). It would be quite absurd to call wings and eyespots homologous because of that – but in a very real sense, the gene network underpinning both is “the same thing”. And there is everything in between. Eyes, for example, share common “master” developmental genes including Pax6/eyeless. They were probably built around homologous cell types (i.e. photoreceptors) in most animals that have them (e.g. Arendt, 2003). Nonetheless, the highly complex eye structures of, say, a squid, a dragonfly and a falcon almost certainly evolved independently. And then there are the strange, confused identities of bird fingers that I talked about on previous occasions. Thus, when we ask the question: “are these two structures homologous?” – there is often no simple yes/no answer. At the very least, you have to ask: at what level?
An ode to diversity
The whole autopod business also highlights the dangers of extrapolation. Scientists believed that the autopod-specific Hox code was invented by tetrapods because their staple experimental fish didn’t have it. But life is a huge, diverse bush. Every twig has its own unique quirks, and we can’t take any of them to represent everything on its branch in every respect. In fact, some of the most popular lab animals – fruit flies, nematode worms, the aforementioned zebrafish – are also among the quirkier denizens of the planet. This is why I find it really really important not to limit ourselves to a few well-worn “model organisms”, not to draw sweeping conclusions from them. Although our common ancestry means that fruit flies or nematodes will in many ways help us understand ourselves, there is no guarantee. Comparative biology thrives on diversity.
(Of course, I say that as an evolutionary biologist working on a non-model organism. I may be somewhat biased ;))
Arendt D (2003) Evolution of eyes and photoreceptor cell types. The International Journal of Developmental Biology 47:563-571
Boisvert CA et al. (2008) The pectoral fin of Panderichthys and the origin of digits. Nature 456:636-638
Davis MC et al. (2007) An autopodial-like pattern of Hox expression in the fins of a basal actinopterygian fish. Nature 447:473-476
De Robertis EM (2008) Evo-devo: Variations on ancestral themes. Cell 132:185-195
Erwin DH & Davidson EH (2002) The last common bilaterian ancestor. Development 129:3021-3032
Freitas R et al. (2007) Biphasic Hoxd gene expression in shark paired fins reveals ancient origin of the distal limb domain. PLoS ONE 2:e754
Johanson Z et al. (2007) Fish fingers: digit homologues in sarcopterygian fish fins. Journal of Experimental Zoology Part B 308:757-768
Keys DN et al. (1999) Recruitment of a hedgehog regulatory circuit in butterfly eyespot evolution. Science 283:532-534
Pueyo JI et al. (2008) Ancestral Notch-mediated segmentation revealed in the cockroach Periplaneta americana. PNAS 105:16614-16619
Rivera AS & Weisblat DA (2009) And Lophotrochozoa makes three: Notch/Hes signaling in annelid segmentation. Development Genes and Evolution 219:37-43
Schneider I et al. (2011) Appendage expression driven by the Hoxd Global Control Region is an ancestral gnathostome feature. PNAS 108:12782-12786
Stollewerk A et al. (2003) Involvement of Notch and Delta genes in spider segmentation. Nature 423:863-865
Tabin CJ et al. (1999) Out on a limb: Parallels in vertebrate and invertebrate limb patterning and the origin of appendages. Integrative and Comparative Biology 39:650-663