Phantom hourglasses

Holy ribosome, I’ve just written close to two thousand words about a paper. I… think I may have got a bit too excited. Or too bogged down in little technical details. Either way, you got lucky. The two-thousand word monster is not what you’re getting.

The reason I got excited about Piasecka et al. (2013) is that it, er, qualifies some other things I’d previously got excited about. And by “qualifies”, I mean turns inside out and performs a thorough autopsy on.

I previously touched upon the idea of the developmental hourglass – meaning that the embryos of related creatures are most similar to each other somewhere in the middle of development. The great rival of this hypothesis is that of early conservation (or the “funnel”), where embryos diverge from a similar starting point. The latter has been around as long as comparative embryology itself. The hourglass is a pretty intriguing pattern and raises all kinds of questions about what causes it – but of course, to have a cause, it has to exist in the first place.

So my previous excitement had been partly about the observation that the hourglass – originally noted in visible traits of embryos – also exists in the changing sets of genes activated throughout development (the transcriptome). According to various papers, genes expressed in mid-embryogenesis are on average older, slower-evolving and behave more similarly across species than genes active at other stages. If such observations are correct, that would certainly indicate that the hourglass is a real thing and something strange is going on with constraints and evolvability.

But, and here comes the Piasecka paper – is it?

This study is huge. There is (to use a highly technical phrase) a fucking shitload of stuff in it. Instead of looking at some big global property of the transcriptome, these authors went into all kinds of detail about various properties of specific sets of genes. They looked at – well, they say they looked at five different measures of evolutionary constraint, but actually some of those are made up of more than one thing, so really it’s quite a bit more than five.

And when they go down to that level of detail, they find that the hourglass is not a universal property of the developmental genetics of zebrafish embryos (unlike Domazet-Lošo and Tautz [2010] reported). Different measures of evolutionary constraint such as the strength of selection against protein-changing mutations, the age of the genes (which is what the original study focused on), or the conservation of their regulatory elements, show different patterns. There are hourglasses, there are a couple of funnels, and then there are parameters that just don’t exhibit much systematic change at all.

(There’s also a couple of points about potentially dodgy statistical approaches in some of these papers, which may make all the difference between an hourglass and a funnel. That’s a bit scary.)

I can’t say I’ve properly digested this paper. There’s an awful lot in it, and, my head was spinning non-stop when I finished reading. It’s definitely fascinating stuff, though, and once again, the conclusion is that things are More Complicated. (I’m kind of getting used to that at this point…) Before, you could look at a group of creatures, compare their development and ask, funnel or hourglass? Then you could ask why. Now, you can’t just make grand generalisations about anything. Taking Piasecka et al. at face value, “funnel or hourglass” is not even a valid question – it depends on exactly what you’re measuring. So much for “laws” of developmental evolution…

***

References:

Domazet-Lošo T & Tautz D (2010) A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns. Nature 468:815-818

Piasecka B et al. (2013) The hourglass and the early conservation models—co-existing patterns of developmental constraints in vertebrates. PLoS Genetics 9: e1003476

Slime moulds don’t play by the rules

I’m starting to think dictyostelids are seriously interesting. These are the guys whose eerily animal-like epithelial tissues prompted the idea of multicellularity being ancestral to the lineage containing animals, choanoflagellates, fungi and amoebae. (Incidentally, Parfrey and Lahr [2013] wrote a nice critical response to that hypothesis – it deserves a post of its own, but not this post.) They are used as model organisms in (evolutionary) developmental biology (Schaap, 2011), a field which is mostly dominated by animals and plants for obvious reasons.

Recently I wrote about the developmental hourglass pattern, which means that the most conserved developmental stages are not the earliest (as Karl von Baer thought at the dawn of comparative embryology), but some way into development. This pattern has been found in several animal phyla both at the morphological level and in various features of developmental gene expression, and it was recently also discovered in plants, which prompted my first post about it.

A group of researchers reckoned they should check how universal the hourglass is, and they thought the slime mould/social amoeba and honoured developmental model organism Dictyostelium is a good place to look (Tian et al., 2013). Unlike plants and animals, which develop from a single cell, the multicellular life stage of dictyostelids is a gathering of thousands of previously independent cells that may not be genetically identical. Therefore, these tiny creatures represent a very different approach to development from our favourite lab animals. Whether or not they still show an hourglass pattern could give clues about the deeper laws that govern all developmental processes.

Dictyostelids turn out to be complete deviants in this respect. Comparisons of the genes two species of Dictyostelium use in their multicellular development show neither von Baer’s “funnel” pattern of similarity nor an hourglass. If you include single-celled stages that aren’t, strictly speaking, “developmental”, similarities of gene expression give a “reverse hourglass” with lowest similarity in the middle. If you only consider the actual multicellular developmental stages, conservation increases towards the end – an “inverted funnel”. Other measures gave Tian et al. largely consistent results – genes expressed later in development were more likely to also be present in the other species, and their sequences were more similar on average.

Now that we have a pattern – what could explain it? The authors speculate that an idea that had been used to explain the hourglass in animals may apply just as well to the inverted funnel of slime moulds. This idea is that the evolvability of a developmental stage depends on the interactions that occur during it. The more interactions between genes/cells/tissues, the worse the effect of a tiny screw-up and the smaller the chance of a beneficial change, hence the most interconnected developmental stages will tend to be most conserved in evolution.

In animals, goes the reasoning, early development is relatively simple, and later development is relatively modular. Early on, there’s less to screw up, whereas later, every screw-up is limited to part of the embryo. In between is the sweet spot where everything talks to everything and a small modification can have large knock-on effects. The result is the hourglass. In slime moulds, however, that later stage when the developing organism is subdivided into semi-independent modules never comes. All tissues keep communicating and affecting each other right up to the point where the multicellular body is fully developed. Thus, if you like, only the first half of the hourglass happens in these creatures.

It’s an interesting idea. I like it.

***

References:

Parfrey LW & Lahr DJG (2013) Multicellularity arose several times in the evolution of eukaryotes. BioEssays advance online publication, 11/01/2013, doi: 10.1002/bies.201200143

Schaap P (2011) Evolutionary crossroads in developmental biology: Dictyostelium discoideum. Development 138:387-396

Tian X et al. (2013) Dictyostelium development shows a novel pattern of evolutionary conservation. Molecular Biology and Evolution advance online publication 16/01/2013, doi: 10.1093/molbev/mst007