Given that disputes over the existence and meaning of the phylotypic stage and the hourglass model have simmered in various forms for a century and a half, the remarkable correspondence between the hourglass model and gene expression divergence discovered by Kalinka and Varga and colleagues would be big news all by itself. But amazingly, that issue of Nature included two distinct reports on the underpinnings of the phylotypic stage. The other article involved work in another venerable model system in genetics, the zebrafish.
The report is titled "A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns" and is co-authored by Tomislav Domazet-Loso and Diethard Tautz. To understand how their work has shed light on the phylotypic stage and the evolution of development, we'll need to look first at an approach to the analysis of evolutionary genetics that these two scientists pioneered: phylostratigraphy.
The authors first described phylostratigraphy in 2007 and have since used the approach to examine genes that cause human genetic disease and cancer. They define it as:
a statistical approach for reconstruction of macroevolutionary trends based on the principle of founder gene formation and punctuated emergence of protein families.
The idea is that every gene has a birthday, a point at which it is first identifiable in evolutionary history. Some genes are ancient, having arisen before there were even complex cells, and others are relative juveniles, having arisen much more recently. Genes present today, then, can (in principle) be assigned an "age." Domazet-Loso and Tautz represent the "age" of a gene by the evolutionary "epoch" in which it appeared, by analogy with the identification of the appearance of biological lineages with stratigraphic epochs in earth's history. So for example, some genes appear with the development of true animals (metazoa), and so these genes are assigned to that "stratum" of biological history. In fact, the authors call each epoch a 'phylostratum' to reinforce that metaphor.
So how does this work? To do phylostratigraphic analysis, you need two major sets of tools. First, you need a pretty solid phylogeny, or family tree, of your organism(s) of interest. Second, you need complete or nearly-complete genome sequences of the organism of interest and of organisms that can represent the major branch points (or nodes) in the family tree. The procedure from there seems clear enough: using a well-known alignment program, you search through the family tree for each of the genes in your organism of interest, to see where it is first recognizable in the phylogeny. That point is the phylostratum from which that gene arises. With that data, you could look at the contributions of various phylostrata to various body parts or processes. Or conversely, you could look at the relative age of the sets of genes associated with those body parts or processes. Or you could look at the relative age of the sets of genes associated with different stages of development. And that's what Domazet-Loso and Tautz did in their Nature paper on the hourglass model.
Specifically, the authors took their phylostratigraphic data and merged it with expression data at various stages of zebrafish development; they called the resulting parameter the transcriptome age index (TAI). Basically, they calculated a relative age of the genes that are turned on at each stage of development, corrected for the extent to which particular genes are being used at those stages. Then they mapped the TAI onto the timeline of zebrafish development. And this is what they saw.
Does that look familiar? Like, say, half an hourglass? In the earliest stages of development, active genes are young-ish, as they are in the juvenile and the adult. In between, the genes that are active are older -- a lot older. And the low point, where genes are oldest? It's the end of segmentation and the beginning of the pharyngula stage. That's the stage that is considered the phylotypic stage in vertebrates. (What this has to do with godless liberalism, I have no idea.) And so we see that hourglass again, this time traced out by the evolutionary age of the genes that are active during the phylotypic stage.
As you look at the graph, you might notice some other interesting periods in the life of a fish. There's a prominent peak of gene youthfulness at 6 hours of development; this corresponds to gastrulation, that wonderful time in your life when you established yourself as a three-layered animal. That peak is due to the activation of a lot of animal-specific genes, namely those that date to the metazoan phylostratum. This includes genes that control cell-cell interactions, certainly a hallmark of animal-building. Those might seem like incredibly basic functions, but they're relatively young compared to even more basic cellular processes, and the genes that control those processes are the ones that predominate during the later phylotypic stage. (The authors showed, in fact, that extremely ancient genes are active uniformly throughout development, whereas the younger gene sets display the hourglass pattern: high-low-high.)
And notice that gene youthfulness declines during aging (after adulthood). Now why would that be? The authors propose that the most recent innovations (facilitated by relatively young genes) are likely to have resulted from adaptation, and so:
The fact that ageing animals revert to older transcriptomes is in line with the notion that animals beyond the reproductive age are not 'visible' to natural selection and can therefore not be subject to specific adaptations any more.
There's a lot more: the study found differences between males and females (look at the dotted lines in the figure), for example. But they also extended their analysis to other animals with known genomes: fruit fly, roundworm and mosquito. In every case they saw the same pattern: young-old-young. Their fly graph displays a pattern strikingly similar to that in the fish, and nicely dovetails with the distinct analysis done by Pavel Tomancak's group:
Look at the low point, where the genes are the oldest. It's the germband elongation stage -- the recognized phylotypic stage for insects, and the same point singled out in the fly paper. Remarkable.
So to summarize, the two papers, reported separately but simultaneously, strongly support the hourglass model of development, in which embryos are seen to converge on an evolutionarily-ancient form, after diverse beginnings and followed by radical divergence into the wonderful variety of animals seen today and in the past. Domazet-Loso and Tautz explain how these new results make sense of the hourglass:
These consistent overall patterns across phyla, as well as the detailed analysis within zebrafish, suggest that there is a link between evolutionary innovations and the emergence of novel genes. Adaptations are expected to occur primarily in response to altered ecological conditions. Juvenile and adults interact much more with ecological factors than embryos, which may even be a cause for fast postzygotic isolation. Similarly, the zygote may also react to environmental constraints, for example, via the amount of yolk provided in the egg. In contrast, mid-embryonic stages around the phylotypic phase are normally not in direct contact with the environment and are therefore less likely to be subject to ecological adaptations and evolutionary change.
And as they note, Darwin himself made this connection, reflecting on von Baer's earlier observations. Ideas, like genes, can have a long and productive history.
[Cross-posted at Quintessence of Dust.]
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Domazet-Lošo, T., & Tautz, D. (2010). A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns. Nature, 468 (7325), 815-818. DOI: 10.1038/nature09632
17 Comments
JGB · 18 December 2010
I'm putting together an overview lecture of basic embryology ideas and how they represent yet another line of evidence for evolution over winter break. What wonderful data to have to incorporate. Right up there with the Neanderthal Genome papers.
Joe Felsenstein · 18 December 2010
There seem to be two explanations around. One is the one you quote from Domazet-Loso and Tautz about the phylotypic stages being those that are in less contact with the environment, hence less modified by natural selection. The other attributes the paucity of modifications of that stage to the multiple effects of modifications early in development, so that these tend to disrupt development more than later modifications. Thus, the argument goes, most modifications of the embryo by natural selection will tend to be late ones.
Is there anything in these recent papers that argues for one of these explanations or the other?
Steve Matheson · 18 December 2010
DS · 18 December 2010
Yet again another independent data set and independent type of analysis and yet another stunning confirmation of the predictions of evolutionary theory. This is one of the most remarkable results that I can remember seeing for avery long time. Also another beautiful example of evo/devo in the age of genomics, coupled with phylogenetics.
Now of course the creationists have no explanation whatsoever for any of these observations. Nor did they do any of the research that led to these discoveries. If they thought that this pattern would not be found, why didn't they try to disprove it themselves. This is yet another data set that can instantly be incorporated in the fight against creationism. I'm sure the authors would be proud to see it used for that purpose.
Now there is still an obnoxious concern troll who is going around derailing threads. He apparently cannot stand for real science to be discussed by anyone. He will no doubt show up on this thread and whine and moan about how no one is discussing the science, or some such equally transparent nonsense. Until Steve can purge the thread of this type of pollution, everyone should ignore the troll and let him starve on a diet of his own vomit.
JGB · 18 December 2010
It would seem that the simplest way to explain the hourglass, is that the relative difficulty of modifying early development is essentially correct. The reason that the earliest development is divergent, is because you have to close the loop so to speak. As animals diverge as adults and their reproductive strategies and environments diverge the starting points for development become more divergent themselves, and what you see then is selection acting to funnel that variability back into the "standard" program. At a first pass that explanation would suggest that the width of the bottom of the hourglass would correlate well with the speciation rate for the taxon, while if it was the environment in general it would tend to correlate somewhat better with absolute divergence time. Whether or not we have a model system at this moment that could give enough data to distinguish that fine a level of detail is another matter.
DS · 19 December 2010
Another interesting thing about this article is the method for determining the age of genes. Apparently new genes arise all of the time, undoubtedly through a process of gene duplication followed by random mutation and natural selection. This of course causes an increase in information, which creationists claim cannot happen. As Joe Felsenstein correctly points out, gene duplication is not necessary in order for information to increase, it simply represents an incontrovertible example with which to confront creationist nonsense.
Now why would god create everything in six days and then keep adding genes periodically every few years. Doesn't seem to make much sense for her to do it that way.
Kris · 19 December 2010
This comment has been moved to The Bathroom Wall.
stevaroni · 19 December 2010
This comment has been moved to The Bathroom Wall.
Steve Matheson · 19 December 2010
Joe Felsenstein · 19 December 2010
Steve Matheson · 19 December 2010
Joe Felsenstein · 19 December 2010
Steve Matheson · 19 December 2010
Henry J · 19 December 2010
Joe Felsenstein · 20 December 2010
eric · 20 December 2010
That fly graph seems to show a big difference in the age of the genes used by adult males (young) and females (old). Do they give an explanation for this?
Using the quote right about the fly chart as a jumping-off point, I would tentatively think that this implies that adult males undergo much stronger selection (maybe not natural selection - could be sexual by females, or some other sort???) than females. But I could easily be getting that wrong.
Rolf Aalberg · 20 December 2010