It’s live! Multigenerational effects stand to change how we think about inheritance, but their significance and evolutionary conservation remain poorly understood. Check out our newest manuscript where we shed some light on this exciting area of biology! https://www.biorxiv.org/content/10.1101/2021.05.07.443118v1

First off, this project was long something I thought would benefit the field, and I’m thrilled that we were able to make it a reality during this last pandemic year, but I could not have done it without amazing help from other intergen labs and researchers.

So shout out to @Reinke_Science @awillis_science @phylewgenetics @Jon_LP @FabianBraukmann @ericmiskalab and members of the Baugh lab (Kinsey and Ryan) for a great collaborative effort in making this study a reality

A twitter summary (1/13) – This work answers a few main questions. Do intergenerational responses to stress represent conserved processes? Are they stress specific? What are the tradeoffs? How commonly are the effects of stress on gene expression maintained transgenerationally?

We also answered these questions in the context of several recent observations of intergenerational effects in C. elegans, which represents one of the powerhouse models of multigenerational research and the mechanisms underlying such effects. #Celegans #worms #intergenerational

Main takeaway (1/5) – Intergen responses to stress clearly play a substantial, stress specific, and evolutionarily conserved role in regulating animal physiology. These effects are also not simply due to the direct effects of stress on germ cells/embryos (see cited studies)

Main takeaway (2/5) – Our findings stand to change how we think about other deleterious intergen effects across species like fetal programming in humans. Are such costly intergen effects mechanistically related to adaptive intergen effects in other species as well? – as seen here

Main takeaway (3/5) – We identified a core set of 279 highly conserved genes that exhibit intergenerational changes in expression in response to stress in all species tested. We propose that these genes are particularly susceptible to intergenerational regulation.

Main takeaway (4/5 part 1) – Surprisingly, we did not detect any conserved transgen effects on gene expression despite assaying multiple stresses previously reported to be capable of eliciting transgen effects. There are many possible explanations for this (see manuscript) but-

Main takeaway (4/5 part 2) – one thing that was clear was that the vast majority of intergen effects on gene exp. are lost or actively erased once the stress is no longer present. This suggests that intergen effects and transgen effects might be independent phenomena! (see paper)

Main takeaway (4/5 part 3) – Alternative option 1 - while intergen effects appear easy to trigger under many circumstances, perhaps transgen effects occur only under specific conditions. Could this tell us something about the underlying biology of these two types of effects?

Main takeaway (4/5 part 4) – Alt. option 2/3 – While intergen effects can change individual somatic gene exp. it’s possible transgen effects are more weakly distributed across many genes, or transgen effects might mainly be present in germ cells and thus eluded our detection here

Main takeaway (4/5 part 5) – There is mounting data for all of these options, and some others, and I’d love to see/do a similar follow up study across labs to answer this and deduce the conditions under which specific stresses trigger intergen vs transgen responses etc…

Main takeaway (5/5) – Why are intergen effects not maintained? Consistent with evolutionary modelling of such effects, we found that these robust adaptations also have significant costs and this likely promotes their loss or active erasure if the stress is no longer present.

End summary – There’s a lot of data in here that I expect will help us think about both intergenerational effects and the vastly underappreciated role they play in biology (my opinion) as well as about how findings in C. elegans might translate to other species. Check it out!

Lastly, I again cannot thank all the labs/people that collaborated on this enough to investigate several different paradigms and reproduce many different effects across labs/countries. Really happy we were able to finish this project despite a very challenging last year.