Månadsarkiv: augusti 2013

From my halftime seminar

Publicerat i english, genetik av

A couple of weeks ago I presented my halftime seminar at IFM Biology, Linköping university. The halftime at our department isn’t a particularly dramatic event, but it means that after you’ve been going for two and a half years (since a typical Swedish PhD programme is four years plus 20% teaching to a total of five years), you get to talk about what you’ve been up to and discuss it with an invited opponent. I talked about combining genetic mapping and gene expression to search for quantitative trait genes for chicken domestication traits, and the work done so far particularly with relative comb mass. To give my esteemed readers an overview of what my project is about, here come a few of my slides about the mapping work — it is described in detail in Johnsson & al (2012). Yes, it does feel very good to write that — shout-outs to all the coauthors! This is part what I said on the seminar, part digression more suited for the blog format. Enjoy!

Slide04(Photo: Dominic Wright)

The common theme of my PhD project is genetic mapping and genetical genomics in an experimental intercross of wild and domestic chickens. The photo shows some of them as chicks. Since plumage colour is one of the things that segregate in this cross, their feathers actually make a very nice illustration of what is going on. We’re interested in traits that differ between wild and domestic chickens, so we use a cross based on a Red Jungefowl male and three domestic White Leghorn females. Their offspring have been mated with each other for several generations, giving rise to what is called an advanced intercross line. Genetic variants that cause differences between White Leghorn and Red Jungefowl chickens will segregate among the birds of the cross, and are mixed by recombination at meiosis. Some of the birds have the Red Junglefowl variant and some have the White Leghorn variant at a given part of their genome. By measuring traits that vary in the cross, and genotyping the birds for a map of genetic markers, we can find chromosomal chunks that are associated with particular traits, i.e. regions of the genome where we’re reasonably confident harbour a variant affecting the trait. These chromosomal chunks tend to be rather large, though, and contain several genes. My job is to use gene expression measurements from the cross to help zero in on the right genes.

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From Lisbon, part 2

Publicerat i dear diary, english av

ESEB 2013 is over. I’ve had a great time, met with a lot of cool people and actually coped reasonably well with the outdoor temperature. As a wimpy Swede, I find anything above 30 degrees Celsius rather unpleasant. There have been too many talks and posters to mention all the good stuff, but here are a few more highlights:

Trudy Mackay’s plenary on epistasis in quantitative traits in D. melanogaster: Starting with the Drosophila Genetic Reference Panel and moving on to the Flyland advanced intercross population, Mackay’s group found what appeared to be extensive epistasis in several quantitative traits. Robert Anholt spoke later the same day about similar results in olfactory behaviour. While most of the genetic variance on the population level is still effectively additive, there seems to be a lot of interaction at the level of gene action, and it hinders QTL detection. The variants that did show up appeared to be involved in common networks. Again, we ask ourself how big these networks are and how conserved they might be among different species.

How did all this epistasis come about then? Mackay’s answer is phenotypic buffering or canalisation (as we say in the Nordic countries: a beloved child has many names). That is, that the organism has a certain buffering capacity against mutations, and that the effect of many of them are only revealed on a certain genetic background where buffering has been broken. See their paper: Huang et al (2012). Mackay mentioned some examples in answer to a question: potentially damaging exonic mutations travelled together with compensatory mutations that possibly made them less damaging. It would be really fun to see an investigation of the molecular basis of some examples.

(Being a domestication genetics person, this immediately brings me to Belyaev’s hypothesis about domestication. Belyaev started the famousic farm fox domestation experiment, selecting foxes for reduced fear of humans. And pretty quickly, the foxes started to become in many respects similar to dogs. Belyaev’s hypothesis is that ‘destabilising selection’ for tameness changed some regulatory system (probably in the hypothalamus–pituitary–adrenal axis) that exposed other kinds of variation. I think it’s essentially a hypothesis about buffering.)

Laurent Excoffier about detecting recent polygenic adaptation in humans. Very impressive! The first part of the talk presented a Fst outlier test applied to whole pathways together instead of individual loci. This seems to me analogous to gene set enrichment tests that calculate some expression statistic on predefined gene sets, instead of calculating the statistic individually and then applying term enrichment tests. In both cases, the point is to detect more subtle changes on the pathway as a whole. As with many other enrichment methods, particularly in humans, it is not that obvious what to do next with the list of annotation terms. Even when the list makes good biological sense — really, is there a gene list that wouldn’t seem to make at least a bit of biological sense? The results do (again) imply epistasis in human immune traits, and that is something that could potentially be tested. Though it would be a heroic amount of work, I hope someone will use this kind of methods in some organism where it is actually possible to test the function and compare locally adapted populations.

Alison Wright’s talk on Z chromosome evolution. She works with Judith Mank, and I’ve heard a bit about it before, but sex chromosomes and the idea that you can trace the ‘strata’ of chromosome evolution are always fascinating. Wright also presented some interesting differences in the male hypermethylated region between birds with different mating systems.

William Jeffery on blind cavefish: I’ve been thinking for ages that I should blog about the blind cavefish (for popular/science and in Swedish, that is), because it’s such a beautiful example. The case for eye regression as an adaptive trait rather than just the loss of an unnecessary structure seems pretty convincing! Making an eye regress at the molecular level seems at once rather simple — removal of the lens (by apoptosis in the blind cavefish) seems to be all that is needed — and complex (it’s polygenic and apparently not achieved the same way in all blind cavefish populations).

Virpi Lummaa’s plenary about using parish records from preindustrial Finland to investigate hypotheses about reproduction, longevity and menopause. I heard about the Grandmother hypothesis ages ago, so I knew about it, but I didn’t know to what extent there was empirical support for it. Unfortunately, that many of the cases where I’ve heard a nice hypothesis but don’t know the empirical support turn out to be disappointments. Not this time, however! On top of all the good stuff in the talk, Lummaa had very pretty slides with old photos and paintings by Albert Edelfelt. The visual qualities were surpassed only by Rich FitzJohn’s slides.

Edelfelt_Larin_Paraske

(Larin Paraske by Albert Edelfelt)

Two things that were not so great:

The poster sessions. Now my poster session on Friday turned out very well for me, but many others weren’t so lucky. I don’t know why half of the posters were hung facing the wall with hardly enough space for people to walk by the poster board, but it was a terrible idea and must have stopped a lot of people from seeing more posters.

The gender balance. According to Julia Schroeder only 27% of invited speakers were women. I don’t know how it worked behind the scenes and what the instructions to symposium organisers were, and there might not be an easy fix, but this urgently needs fixing.

Of course, there were many more good talks and posters than the handful I’ve mentioned, and apart from them, the twitter feed and tweetup, the social gatherings and the fact that there were actually several interesting people that came to my poster to chat were highlights for me. I come home with a long list of papers to read and several pages of things to try. Good times!

lisbon

From Lisbon

Publicerat i dear diary, english, evolution av

Dear diary,

I’m at the Congress of the European Society for Evolutionary Biology in Lisbon. It’s great, of course and I expected nothing less, but there is so much of it! Every session at ESEB has nine symposia running in parallel, so there are many paths through the conference programme. Mine contains a lot of genomics for obvious reasons.

Some highlights so far:

Juliette de Meaux’s plenary: while talking about molecular basis of adaptations in Arabidopsis thaliana — one study based on a candidate gene and one on a large-effect QTL — de Meaux brought up two fun concepts that would recur in Thomas Mitchel-Olds’ talk and elsewhere:

1) The ‘mutational target’ and how many genes there are that could possibly be perturbed to change a trait in question. The size of the mutational target and the knowledge of the mechanisms underlying the trait of course affects whether it is fruitful to try any candidate gene approaches. My intuition is to be skeptical of candidate gene studies for complex traits, but as in the case of plant pathogen defense (or melanin synthesis for pigmentation — another example that got a lot of attention in several talks), if there is only one enzyme pathway to synthesise a compound and only one step that controls the rate of the reaction, there will be very few genes that can physically be altered to affect the trait.

2) Some of both de Meaux’s and Mitchel-Olds’ work exemplify the mapping of intermediate molecular phenotypes to get at small-effect variants for organismal traits — the idea being that while there might be many loci and large environmental effects on the organismal traits, they will act through different molecular intermediates and the intermediate traits will be simpler. The intermediate traits might be flagellin bindning, flux through an enzymatic pathway or maybe transcript abundance — this is a similar line of thinking as the motivations for using genetical genomics and eQTL mapping.

The ”Do QTN generally exist?” symposium: my favourite symposium so far. (Note: QTN stands for Quantitative Trait Nucleotide, and it means nothing more than a known causal sequence variant for some quantitative trait. Very few actual QTN featured in the session, so maybe it should’ve been called ”Do QTG generally exist?” Whatever.) I’ve heard both him and Annalise Paaby present their RNA inference experiments revealing cryptic genetic variation in C. elegans before, but Matt Rockman also talked about some conceptual points (”things we all know but sometimes forget” [I’m paraphrasing from memory]): adaptation does not require fixation; standing variation matters; effect-size is not an intrinsic feature of an allele. There was also a very memorable question at the end, asking whether the answer to the questions Rockman posed at the beginning, ”What number of loci contribute to adaptive evolution?” and ”What is the effect-size distribution?” should be ”any number of loci” and ”any distribution” … To which Rockman answered that those were pretty much his views.

In the same symposium, Luisa Pallares, showed some really nice genome wide association result for craniofacial morphology from natural hybrid mice. As someone who works on an experimental cross of animals, I found the idea very exciting, and of course I immediately started dreaming about hybrid genetical genomics.

Dieter Ebert’s plenary: how they with lots of work seem to have found actual live Red Queen dynamics with Daphnia magna and Pasteuria ramosa.

Larry Young and Hanna Kokko: Young and Kokko had two very different invited talks back to back in the sex role symposium, Young about the neurological basis of pair-bonding in the famous monogamous voles, and Kokko about models of evolution of some aspects of sex roles.

Susan Johnston‘s talk: about how heterozygote advantage maintains variation at a horn locus in the Soay sheep of St Kilda. Simply awesome presentation and results. Published yesterday!

On to our stuff! Dominic Wright had a talk presenting our chicken comb work in the QTN session, and on Friday I will have a poster on display about the behaviour side of the project. There’s actually quite a few of us from the AVIAN group here, most of them also presenting posters on Friday (Anna-Carin, Johan, Amir, Magnus, Hanne, Rie). And (though misspelled) my name is on the abstract of Per Jensen‘s talk as well, making this my personal record for conference contribution.

The poster sessions are very crowded and a lot of the posters are hung facing the wall with very little space for walking past, and some of them behind pillars. In all probability there’s a greater than 0.5 chance that my poster will be in a horrible spot. But if you happen to be curious feel free to grab me anywhere you see me, or tweet at me.

I looke like this when posing with statues or when I’m visibly troubled by the sunlight. If you’re into genetical genomics for QTG identification, domestication and that kind of stuff, this is the hairy beast you should talk too.

martin_eseb