*Featured image photo credit: Lisandro Milocco

In this episode, Lisandro Milocco (PhD candidate, advised by Dr. Isaac Salazar-Ciudad) shares insights from his new paper, Milocco and Salazar-Ciudad 2022: ‘Evolution of the G matrix under nonlinear genotype-phenotype maps.’ We discuss how Lisandro likes to think about genotype-phenotype maps, how genes control complex developmental processes such as the generation of mammalian teeth, and how the interaction of genes and the developmental processes they control change our expectations for how quantitative phenotypes evolve. Listen to our conversation and then read Lisandro’s full paper here!

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Want to develop your understanding even further? Email Lisandro at lisandro.milocco@helsinki.fi.

NATURALIST SELECTIONS IS AN INTERVIEW SERIES PRODUCED BY THE AMERICAN SOCIETY OF NATURALISTS GRADUATE COUNCIL. WE SHOWCASE GRADUATE STUDENT AND POSTDOC AUTHORED WORK IN THE AMERICAN NATURALIST, A PREMIER PEER-REVIEWED JOURNAL FOR ECOLOGY, EVOLUTION, AND ANIMAL BEHAVIOR RESEARCH. CATCH UP ON EXCITING NEW PAPERS YOU MAY HAVE MISSED FROM THE JOURNAL, AND MEET SOME TRULY BRILLIANT EARLY CAREER NATURALISTS!

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Credits

Featured Guest: Lisandro Milocco, University of Helsinki, Finland

Host, Editor, Producer: Sarah McPeek, University of Virginia, US

Original Music: Daniel Nondorf, University of Virginia, US

Transcript:

You’re listening to Naturalist Selections, a science podcast featuring graduate student and postdoc-authored research in The American Naturalist, produced by the American Society of Naturalists Graduate Council. I’m grad council rep Sarah McPeek and today I’m talking with graduate student first-author Lisandro Milocco! Lisandro is finishing up his PhD with Dr. Isaac Salazar-Ciudad at the University of Helsinki, Finland. His paper is called: “Evolution of the G matrix under nonlinear genotype-phenotype maps.” In the field of quantitative genetics, A G matrix is a statistical summary of the additive genetic basis of a phenotype in a population. G matrices are important evolutionary tools for understanding how natural selection has shaped genetic variance in the past and predicting how phenotypes may continue to respond to selection in the future. Typically, geneticists assume a linear relationship between the G matrix and the phenotype it produces, causing G to remain constant for long periods of a population’s evolution. However, this assumption of linearity does not reflect the fact that many of the genes involved in producing a trait control complex developmental processes that ultimately generate the adult phenotype. Lisandro views development as a critical and fundamentally nonlinear intermediary between a population’s G matrix and its average phenotype. Can G change more dramatically if we incorporate an evolutionary developmental approach? In the paper, Lisandro uses his lab’s longstanding simulation model of mammalian tooth development to explore how complex processes during development shift our expectations for the evolution of G. In the model, small groups of genes specify 21 developmental parameters that interactively guide the formation of the cusps and valleys of the adult tooth. For each simulation, he chooses a different phenotypic optimum for tooth shape and allows the population to evolve toward that optimum under selection, tracking how G changes along the way. He finds that the size and shape of G can change rapidly as a result of the complex gene interactions that occur during tooth development. A slight change in the alleles controlling one developmental parameter can have cascading effects on the entire developmental process, resulting in a very distinct tooth morphology, and consequently, a different relationship between phenotypes and the genes that underly their development. His work suggests that predicting phenotypic evolution using quantitative genotype-phenotype maps requires a thorough understanding of how genes control phenotypic development. I spoke to Lisandro to further develop my own understanding of these complex interactions.

Sarah

I feel like every time I think that I’m close to understanding GPM, someone says something that totally throws me off what I thought it was. So I would love it if you would explain a little bit about how you personally think about genotype to phenotype maps.

Lisandro

Yeah, absolutely. So for me, the genotype-phenotype map, in a way, it’s a mapping function that assigns phenotypes to a genotype. But the main thing about it is that it is a representation of the generative process that creates the phenotype. Right. So that process is ultimately development. So basically, the genes, for example, play a very important role in the developmental process. But there’s also interaction with other things such as biophysical properties of the cells and mechanical properties, etc. And that also feed back into the developmental process. So in a way that the kind of development can be seen as a sort of like an origami. When you fold the paper to create that, you start from a flat paper and then you fold it and you create this three dimensional shape. So in a way, for my understanding of the genotype phenotype map is that it summarizes this complex folding process and the creation of the phenotype. And particularly it kind of summarizes it in a way that is compatible with a lot of mathematical formalism. So that’s why it’s particularly useful for me, because it can be incorporated into models and things like that.

Sarah

Oh, I like this folding paper metaphor you bring up. So do you think of the paper itself is the G and then the way it’s folded?

Lisandro

Right. So maybe development I would say that maybe development could be the series of steps that you need to follow. So you need to follow the paper here, and then you need to twist it and follow it there. So in a way, development kind of summarizes all those steps that allow us to produce the final shape in the end? That’s a very complex thing. Of course, there’s allegory with the origami it’s hard to say what are genes and et cetera. But the important thing is that there’s a complex process that can in principle, be summarized by a metaphor such as the genotype-phenotype map.

Sarah

Yeah. That also makes me think of tooth development specifically, because I don’t know a lot about two development, but the way that you described it in the paper sounded somewhat akin to an origami-like process. Would you say that’s accurate?

Lisandro

Yeah, one can say so, of course, in a very simplified way. But yeah, tooth development is an interesting process because it also starts from, like a flat sheet of cells and basically within this sheet of cells, there’s buckling and folding. That kind of ends up resulting in mountains and valleys that then become cusps and valleys of the teeth. So in a way, it is somewhat similar. But the important thing is that there is not a hand that’s holding the paper as in an origami. But this is actually an internal process of the developmental system which makes it even more complex and interesting really. So, for example, with tooth development, all this folding and buckling results from differential growth of the cells. So some cells divide faster than others, and that creates this buckling. Kind of like the idea that the process itself kind of generates the form. I think it’s very important and interesting. Yeah.

Sarah

So there’s the mechanical constraints of how cells can move and which cells can divide when. But then there are also all of the signaling cascades that are going on to program when that happens. And. Oh, that’s complicated.

Lisandro

Exactly. Yeah. And everything is kind of interdependent on each other. For example, during tooth development, there’s a transmission of certain signaling centers that kind of direct surrounding cells to divide faster, but the signal themselves do not divide. And then it’s interesting because the signaling centers also have a certain inhibitory region. So you cannot have two of these too close to each other. Basically, this signaling process is occurring at the same time as the tissue is folding. So then you have even more of a feedback here going on because, of course, if this tissue folds a certain way, then the signaling centers will be distanced in different ways.

Sarah

Wow.

Lisandro

Of course, this type of thing takes years and years of developmental biology research to be able to get into even having candidate genes and how they interact and things like that.

Sarah

So the lab that you worked in for your PhD has done a lot of this work. It looked like it was in ringed seals as the animal model? That’s so cool!

Lisandro

Yeah. It’s very interesting, actually. Here at the University