About the author: Sarah McPeek is a PhD candidate with Dr. Butch Brodie at the University of Virginia in Charlottesville, VA. Her research focuses on the evolution of behavioral interactions among nectar-producing woodland wildflowers and nectar-foraging beetles at Mountain Lake Biological Station. She previously earned her bachelor of the arts at Kenyon College in Ohio in 2019, where she studied the evolutionary ecology of bird flight with Dr. Natalie Wright. Follow Sarah’s work @sarahjmcpeek and read more science writing at sarahjmcpeek.com.
The environment contains genes. Specifically, the genes expressed in one individual can impact the phenotypic expression of another individual in their group. A fish’s antipredator behavior depends in part on how other members of its school respond to a threat. A plant’s root structure depends in part on the growth patterns of its neighbors in the soil. How do these Indirect Genetic Effects (IGEs) change the way we examine phenotypic expression and phenotypic evolution? Further, how can a firm understanding of IGEs impact our efforts to conserve wildlife, manage agricultural landscapes, and treat infectious diseases?
The 2020 AGA President’s Symposium on Indirect Genetic Effects, organized by AGA president Kim Hughes, brought together biologists from a wide array of subdisciplines for a fascinating series of seminars and discussions. The talks ranged from theoretical treatments of IGEs in game theory and disease modeling to empirical tests of IGEs among laboratory-reared populations of mice and fruit flies as well as wild populations of squirrels, songbirds, ants, and weedy plants, to name just a few. You can read more detailed descriptions of individual talks in the Symposium Snippets [links].
To capstone these exciting and constructive meetings, I reached out to symposium speakers about the big picture of IGEs. Here’s what they said about the exciting present and future directions for the field:
- What is the most exciting idea or application to emerge from your own work on indirect genetic effects?
Amelie Baud (European Bioinformatics Institute and University of California San Diego, US): I have shown that IGE from cage mates in laboratory mice can affect not only behavioural and immune phenotypes – which we expected, a priori, to be affected by the behaviour and immune status of cage mates – but also phenotypes such as body weight, glycemia, and wound healing, which we did not think would be affected by cage mates. These surprising results led me to realize that our priors on which phenotypes might be affected by IGE were based largely on the possibility for a given phenotype of interest to be affected by the *same trait* of cage mates… a mechanism that I call “phenotypic contagion”… this means we need to look further, we need to have a broader understanding of the mechanisms of IGE, and I am excited to be now developing data-driven approaches to identify traits of cage mates mediating IGE. One of these approaches is the genome-wide association of IGE, which I think has great potential, and I plan to develop more approaches to discover new ways whereby mice in a cage influence each other, which hopefully will help understand social influences in our own species.
Bronwyn Bleakley (Stonehill College, US): Most studies of IGEs focus on antagonistic interactions, while my work focuses on cooperative interactions. From a basic research perspective, this helps us to understand how cooperation might evolve among unrelated individuals, a problem that has much less data compared to questions about cooperation among relatives. From an applied standpoint, the focus of most studies on antagonistic interactions leaves a large, almost entirely unexplored world of questions about how IGEs might be leveraged to support animal welfare outcomes, crop success, reforestation, and other conservation outcomes that require the successful integration of individuals into populations or communities.
David Rand (Brown University, US): I am excited to explore how GxE effects overlap with GxG effects. Traditionally GxE and epistasis are considered different things, but our experiments show, at least for epistasis between mitochondrial and nuclear genes, that GxE and GxG overlap for complex traits. Our transcriptional studies show this overlap as well and point to specific transcription factors that may underlie a common mechanism.
Joel McGlothlin (Virginia Tech, US): There are two main ways that people have modeled indirect genetic effects—the trait-based model that Allen Moore, Butch Brodie, and Jason Wolf developed in the 1990s, and the variance-components model that Piter Bijma and colleagues developed in the 2000s based on early work by Griffing in the 1960s and 1970s. These two approaches go even further back in the maternal effects literature. When I started working on indirect genetic effects, I was confused by these two approaches, and I thought there should be a way to translate between the two models. So to me, the most exciting result to come out of my work was showing that the two modeling approaches are saying the same thing in different ways. I’m really proud of the paper (McGlothlin and Brodie 2009) where we show that psi (ψ) can be estimated as a function of variance components. It’s interesting, though, that this method hasn’t really been used very often. It’s possible that the kinds of datasets you’d need to do it are too difficult to collect, but I do still hope that some more applications of that method will eventually emerge.
Piter Bijma (Wageningen University, Netherlands): I recently discovered that IGE make a very large contribution to the heritable variation in the prevalence of infectious diseases. This (should) completely change our view on the response to selection in infectious diseases. The prevalence can show much greater response to selection than currently believed, there is a large effect of kin/multilevel selection, and selection can completely remove an infectious disease from a population.
- After hearing everyone’s presentations and engaging in discussion sessions, what do you think are the big open questions in indirect genetic effects?
Alastair Wilson (University of Exeter, UK): The area that really struck me was about how social environments get distributed. So what IGEs do to evolutionary dynamics has to depend on the distribution of social environments… we are modelling the role of IGEs given the distribution of social environments (which we assume in a model or impose in an experiment), but how labile is that distribution, what determines it, and what happens if it changes? And how do we handle the complexity in our models that arises if individuals/genotypes have some degree of control over the social environments they experience?!?
Edmund “Butch” Brodie (University of Virginia, US): I was really excited by the ability to map specific genetic regions to indirect effects. I think this will be a future growth area that helps people really get hold of a somewhat nebulous idea about pathways. Identifying “a gene” or region that contributes to phenotypic variation in social partners is a big step on this road. The other direction that seems especially exciting is how evolvable are things like psi, the parameter that describes [an individual’s phenotypic] response to social context, and Cij, the [phenotypic] assortment [of group members] that generates social context. If these are evolvable, we have identified a mechanism by which individuals can ameliorate negative fitness consequences of interaction, or mediate plastic effects of social neighborhoods.
Nancy Chen (University of Rochester, US): Seems to me that there is still a need for more empirical tests of many theories in more diverse study systems. Theory-wise, I think there are still many questions about how to model indirect genetic effects when there are multiple social partners (seems like there were many questions about dilution parameters and chatter about social networks).
Nathan Bailey (St. Andrews University, UK): The biggest one is: how important are IGEs to the basic outcomes of evolution by natural selection? We know from well-established theoretical work that IGEs can, in principle, change the direction and pace of evolution dramatically. Yet it remains an open empirical question as to whether and how that pans out in natural systems. There are tantalizing indicators that IGEs could have evolutionary consequences that in some cases are of a similar order of magnitude to those of direct genetic effects. I would be excited to see the field comprehensively put this idea to the test. The time seems right to conduct large-scale, collaborative projects that experimentally manipulate IGEs, measure their effects on evolutionary responses to selection, and then dissect the underlying genetic mechanisms. It was encouraging and fun to see presentations at the conference from a number of groups working in this general direction.
Niels Dingemanse (University of Munich, Germany): Is there (genetic) variation in Psi [the strength of one individual’s phenotypic effect on their social partner]? What are the ecological factors shaping selection on Psi? Is variation in Psi maintained by adaptive processes in natural populations? Is Psi or “social responsiveness” a component of a life-history strategy, i.e. is it integrated with other phenotypic traits?
- The meetings brought together researchers from many different subfields to share how these ideas can apply broadly across all these areas of biology. Based on what you heard and shared at the symposium,why do we need a cross-disciplinary understanding of indirect genetic effects?
Allen Moore (University of Georgia, US): From its inception, quantitative genetics (and indeed genetics) has been concerned with providing an understanding of evolution and [discovering] applications across agriculture and human health. If IGE theory is general and a natural extension of basic quantitative genetics, then it too should find a home in evolution, agriculture, and health. Most importantly, the three inform each other. There is a practical side that the applied fields bring; how do you measure the components of IGE theory? How do you design experiments to investigate IGE? The theoretical side is influenced more from evolutionary biologists, but there is practical evolutionary biology as well. How do IGEs help us understand biodiversity? How do IGEs help explain social interactions and their effects? What areas of evolutionary biology are influenced by IGEs other than behavior (interspecific interactions? Mito-nuclear interactions)? The cross-disciplinary understanding helps identify the commonality across biology. Indeed, by examining IGEs from a cross-disciplinary perspective we see new areas to investigate such as GWAS and focal genes as mechanisms of IGEs.
Andrew McAdam (University of Colorado, US): There are many people interested in similar questions but from different perspectives. We need to be careful not to re-invent the wheel. We can also borrow ideas, tools and perspectives from other sub-fields to gain a better understanding of our system. For example, most of what we think of as ’social’ effects are not at all what many behavioural ecologists think of as social. We tend to focus on more tractable (usually dyadic) interactions in often controlled situations. But contrast this with the mess of social interactions in a gregarious species in nature. Bridging this gap is a huge challenge, but this is ultimately where we need to go.
Camille Desjonquères (University of Wisconsin-Milwaulkee, US): One thing that I found a bit confusing [from the meetings] is the different names and terms that are used to describe similar things. It would be good to synthesize all the names and approaches ([e.g.,] making parallels between the animal model and the variance partition approach). I expect this will (a) help cross-disciplinary understanding of IGEs and (b) better focus the field on the most pressing questions.
David Westneat (University of Kentucky, US): For me, is it is just fun and stimulating to hear about alternative approaches to similar questions. But more fundamentally, social interactions are complicated in many ways, and the understanding of how they evolve has been a major challenge since before Darwin. Multiple perspectives arising from multiple systems will be necessary to fully address this complexity. It can be bewildering at times, but I think the struggle of blending perspectives into something coherent is worth it in this case.
Michael Wade (Indiana University Bloomington, US): I believe that we need a cross-disciplinary investigation and discussion of IGEs because they span so many kinds of intra and inter-specific interactions and so many concepts (plasticity, G x E, host-symbiont coevolution, sexual selection, host-pathogen coevolution, kin selection, cooperation and conflict, mito-nuclear coevolution). If each area had to discover IGEs for themselves, it would happen very slowly and in some areas… it might never penetrate at all. This impedes our understanding of a unified evolutionary science instead of [remaining] a bunch of more or less isolated fields.
Thanks to everyone who gave me such thoughtful comments on the present and future of IGEs. Also keep an eye out for the Journal of Heredity 2022 special issue on IGEs featuring collaborative perspectives and cutting-edge research from symposium contributors.