phylotypic stages and evolutionary development: part iii -- fish and more

8/6/2019 Phylotypic stages and evolutionary development: Part III -- Fish and more.

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Its just a stage. A phylotypic stage. Part III: Fish and more.

by Stephen F. MathesonOriginally posted on Panda's Thumb, December 2010.

Given that disputes over the existence and meaning of the phylotypic stage and the hourglassmodel 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 andcolleagues would be big news all by itself. But amazingly, that issue ofNature included two distinctreports 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 ontogeneticdivergence patterns" and is co-authored byTomislav Domazet-Losoand Diethard Tautz. Tounderstand how their work has shed light on the phylotypic stage and the evolution ofdevelopment, well need to look first at an approach to the analysis of evolutionary genetics thatthese 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 andcancer. They define it as:

a statistical approach for reconstruction of macroevolutionary trends based on theprinciple 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 evolutionaryhistory. Some genes are ancient, having arisen before there were even complex cells, and others arerelative 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 biologicallineages with stratigraphic epochs in earths history. So for example, some genes appear with thedevelopment 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 solidphylogeny, or family tree, of your organism(s) of interest. Second, you needcomplete or nearly-complete genome sequences of the organism of interest and of organisms thatcan represent the major branch points (or nodes) in the family tree. The procedure from thereseems clear enough: using a well-known alignment program, you search through the family tree foreach 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 thecontributions of various phylostrata to various body parts or processes. Or conversely, you couldlook at the relative age of the sets of genes associated with those body parts or processes. Or youcould look at the relative age of the sets of genes associated with different stages of development.

And thats 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 atvarious stages of zebrafish development; they called the resulting parameter the transcriptome ageindex (TAI). Basically, they calculated a relative age of the genes that are turned on at each stage ofdevelopment, 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.

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Does that look familiar? Like, say, half an hourglass? In the earliest stages of development, activegenes are young-ish, as they are in the juvenile and the adult. In between, the genes that are activeare older a lot older. And the low point, where genes are oldest? Its the end of segmentation andthe beginning of the pharyngula stage. Thats the stage that is considered the phylotypic stage in

vertebrates. And so we see that hourglass again, this time traced out by the evolutionary age of thegenes 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.Theres a prominent peak of gene youthfulness at 6 hours of development; this corresponds togastrulation, that wonderful time in your life when you established yourself as a three-layeredanimal. That peak is due to the activation of a lot of animal-specific genes, namely those that dateto the metazoan phylostratum. This includes genes that control cell-cell interactions, certainly ahallmark of animal-building. Those might seem like incredibly basic functions, but theyrerelatively 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, infact, that extremely ancient genes are active uniformly throughout development, whereas theyounger 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) arelikely to have resulted from adaptation, and so:

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The fact that ageing animals revert to older transcriptomes is in line with the notionthat animals beyond the reproductive age are not visible to natural selection and cantherefore not be subject to specific adaptations any more.

Theres a lot more: the study found differences between males and females (look at the dotted linesin the figure), for example. But they also extended their analysis to other animals with known

genomes: fruit fly, roundworm andmosquito. 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 dovetailswith the distinct analysis done by Pavel Tomancaks group:

Look at the low point, where the genes are the oldest. Its the germband elongation stage therecognized 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 thehourglass 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 newresults make sense of the hourglass:

These consistent overall patterns across phyla, as well as the detailed analysis withinzebrafish, suggest that there is a link between evolutionary innovations and theemergence of novel genes. Adaptations are expected to occur primarily in response to

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altered ecological conditions. Juvenile and adults interact much more with ecologicalfactors than embryos, which may even be a cause for fast postzygotic isolation.Similarly, the zygote may also react to environmental constraints, for example, via theamount of yolk provided in the egg. In contrast, mid-embryonic stages around thephylotypic phase are normally not in direct contact with the environment and aretherefore less likely to be subject to ecological adaptations and evolutionary change.

And as they note,Darwin himself made this connection, reflecting on von Baers earlierobservations. Ideas, like genes, can have a long and productive history.

Domazet-Loo, T., & Tautz, D. (2010). A phylogenetically based transcriptome age index mirrorsontogenetic divergence patterns. Nature, 468 (7325), 815-818. DOI: 10.1038/nature09632.

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phylotypic stages and evolutionary development: part iii -- fish and more

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