Intergenerational adaptations to stress are evolutionarily conserved, stress-specific, and have deleterious trade-offs

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1. 

   eLife

   Jul 18, 2022

   Author Response

   Reviewer #1 (Public Review):

   The general idea of comparing response patterns to stress in the offspring generation is new and very interesting.

   We thank Reviewer 1 for their time and thoughtful comments. We agree that these comparisons are new and very interesting and have added multiple revised analyses to the manuscript based on the reviewer comments that we think will further enhance the impact of and conclusions made in this study.

   However, the data that are presented are in several ways preliminary. The phenotype comparisons are mostly convincing, although statistical treatments are partly unclear, given that each "replicate" includes itself many individuals.

   The statistical treatments for groups of individuals are the same as in Burton et al., 2017, Burton et al., 2020, and Willis et al., 2021 which include …

   Author Response

   Reviewer #1 (Public Review):

   The general idea of comparing response patterns to stress in the offspring generation is new and very interesting.

   We thank Reviewer 1 for their time and thoughtful comments. We agree that these comparisons are new and very interesting and have added multiple revised analyses to the manuscript based on the reviewer comments that we think will further enhance the impact of and conclusions made in this study.

   However, the data that are presented are in several ways preliminary. The phenotype comparisons are mostly convincing, although statistical treatments are partly unclear, given that each "replicate" includes itself many individuals.

   The statistical treatments for groups of individuals are the same as in Burton et al., 2017, Burton et al., 2020, and Willis et al., 2021 which include the original reports of the intergenerational responses studied here. Replicates that include many individuals are relatively common when working with C. elegans and are usually compared using ANOVA or student’s t-tests (depending on the number of comparisons) to analyze the variation in batch effects as well as differences between populations of animals.

   We believe this ability to assay hundreds or even thousands of animals, in total, for each comparison in this study makes our data substantially stronger and more reliable. However we are happy to perform any additional statistical tests the reviewer might want to see.

   The transcriptomic data are minimal (only three replicates)

   To address this comment we compared our original three replicates of RNA-seq from F1 animals from C. elegans parents exposed to P. vranovensis BIGb0446 to a second independent three replicates of F1 animals from C. elegans parents exposed to a second P. vranovensis isolate (BIGb0427 – the data for this second P. vranovensis isolate was already part of Fig. 4 of this manuscript).

   By comparing these three new replicates to our previous findings from three original replicates we found that 515 of the 562 genes that exhibited a >2-fold change and were significant at padj <0.01 in the original three replicates were also changed at >2-fold and padj <0.01 in the new three replicates. We believe our findings that 91.6% of genes change >2-fold and remain significant at padj<0.01 even when the number of replicates is doubled (and a different isolate of P. vranovensis is used!) suggests that adding additional replicates would not substantially change the conclusions of this manuscript.

   We would also like to highlight, as above, that because this analysis was done on populations of thousands of similarly staged animals, as opposed to individuals, that this further reduces the variability between replicates. In addition, much of our transcriptomic data from each species was then compared across species and genes were only analyzed for those that changed in multiple different species which themselves each represent a separate three additional replicates [ie genes that change in all 4 species analyzed have to exhibit significant (>2-fold, padj <0.01) changes across 12 total replicates].

   Our new findings comparing six replicates did not substantially change the number of genes identified when compared to using three replicates, and the fact that for all of the main conclusions of this manuscript each set of triplicates from one species was then compared across 9 additional replicates from three other species from pools of thousands of animals makes us very confident that our results are robust and highly reproducible.

   and lack comparison to the stress responses in the parental animals.

   We agree with Reviewer 1 that comparisons to parental animals are interesting and important. Comparisons of F1 progeny gene expression patterns to parental animals were not included here because such comparisons were previously published in some of our original reports of these intergenerational effects (For example, see Burton et al., 2020). In summary, we found that most, but not all, of the effects on gene expression in F1 animals were also detected in parental animals. However, the transcriptional responses only turn on in F1 animals post gastrulation and do not appear to be due to the simple deposition of parental mRNAs into embryos (Burton et al., 2020).

   We have updated the text to highlight these findings.

   The analysis of the transcriptome data is limited to counting overlaps between significantly changed genes, without deeper discussion of the genes and pathways that are affected.

   In the revised manuscript we have completely redone all of the transcriptomic analysis to use a stricter set of cutoffs for significance – both padj <0.01 and requiring a >2-fold change in expression based on the helpful comments of Reviewer 1 – which we agree with – see below.

   As part of this new analysis we have now also included a deeper discussion of the genes that exhibited similar changes across species, including using g:Profiler to examine the genes that exhibited changes across all four species.

   In addition, we have now paired our phenotypic and transcriptomic data across species to identify 19 new genes that we predict are highly likely to be involved in intergenerational responses to stress based on their expression patterns across species. These 19 genes come out of highly filtered analyses across species that identified a total of 23 genes that change only in species that adapt to P. vranovensis or osmotic stress and not in species that do not adapt.

   Interestingly, this analysis identified nearly all of the previously known genes involved in intergenerational adaptations to these stresses including rhy-1, cysl-1, cysl-2 and gpdh-1. Thus, we predict the remaining 19 genes that came out of this analysis are highly likely to be involved in the responses to these stresses. Furthermore, in the revised text we highlight that our new list of 19 genes includes multiple conserved factors that are required for animal viability including genes involved in nuclear transport (imb-1 and xpo-2), the CDC25 phosphatase ortholog cdc-25.1, and the PTEN tumor suppressor ortholog daf-18. This new analysis will likely form the basis for future investigations into the mechanisms underlying these exciting intergenerational effects.

   We believe this additional analysis greatly improves this manuscript. We are also happy to include any specific additional analysis the reviewer would like to see.

   The top response genes that are directly tested have been discovered before. Hence, while interesting patterns are evident from the data, this work largely confirms prior work, including that described in Burton et al. 2020.

   We have revised the text to highlight that the aims of this particular study were to determine if multigenerational responses to stress were evolutionarily conserved at any level, as well as to determine the potential costs of such effects and the specificity of the responses. Questions that were not addressed in any previous study of multigenerational effects, including Burton et al., 2020. Because of the aims of this study we believe it was critical to focus on genes that had an established role in these intergenerational responses in C. elegans and to compare and contrast the behavior and requirement of these genes in intergenerational responses in other species. (Although we note that this newly revised manuscript we have now also reported 19 new top response genes – see above).

   In addition to our original goals, in this study we were able to determine the extent to which intergenerational transcriptional responses are conserved and the extent to which intergenerational transcriptional changes persist transgenerationally (which we find to be effectively not at all using our revised stricter analysis). We believe these findings are not only novel, but perhaps will be surprising to much of the intergenerational and transgenerational field and have a major impact on both how multigenerational studies are interpreted and how they are conducted in the future. This is especially the case for studies in C. elegans which is one of the leading model organisms to study the mechanisms underlying both intergenerational and transgenerational responses to stress.

   For example, we note that several landmark studies of transgenerational effects (persisting into F3 or later generations) in C. elegans performed RNA-seq on F1 progeny (For example, Moore et al., Cell 2019 or Ma et al., Nature Cell Biology 2019). Our new findings reported here suggest that it is possible that none of the transcriptional effects detected in F1 animals will persist in F3 progeny. Furthermore, our studies demonstrate the importance of comparing C. elegans transcriptional effects to related Caenorhabditis species as we found that only a subset of the effects detected in C. elegans are conserved in any other Caenorhabditis species. (Such comparisons are important for determining if and to what extent observations of intergenerational and/or transgenerational effects observed in C. elegans represent conserved phenomena).

   For all of these reasons we believe our data is highly exciting, will be of broad interest to the field, and represent novel and potentially unexpected findings that were not previously reported in any prior work including Burton et al., 2020.

   Reviewer #2 (Public Review):

   Transgenerational effects (TE) (usually defined as multigenerational effects lasting for at least three generations) generated a lot of interest in recent years but the adaptive value of such effects is unclear. In order to understand the scope for adaptive TE we need to understand i) whether such effects are common; ii) whether they are stress-specific; and iii) if there are trade-offs with respect to performance in different environments. The last point is particularly important because F1, F2 and F3 descendants may encounter very different environments. On the other hand, intergenerational effects (lasting for one or two generations) are relatively common and can play an important role in evolutionary processes. However, we do not know whether intergenerational and transgenerational effects have same underlying mechanisms.

   This study makes a big step towards resolving these questions and strongly advances our understanding of both phenomena. Much of the previous work on mechanisms of multigenerational effects has been conducted in C. elegans and this works uses the same approach. They focus on bacterial infection, Microsporidia infection, larval starvation and osmotic stress. I did not quite understand why the authors chose to focus on P. vranovensis rather than P. aeruginosa P14 that has been used in previous studies of transgenerational effects in C. elegans. However, this is a minor point because I guess they were interested in broad transgenerational responses to bacterial infection rather than in strain-specific ones. The authors used different Caenorhabditis species, which is another strength of this study in addition to using multiple stresses.

   We thank the reviewer for these comments. We’d like to briefly highlight that P. vranovensis was also shown to elicit the same transgenerational effects as P. aeruginosa in the bioRxiv version of the same papers that reported transgenerational effects for P. aeruginosa (Kaletsky et al., 2020 – GRb0427 is an isolate of P. vranovensis).

   It is not clear to us why this result was not included in the final published version of this manuscript, but we in fact used P. vranovensis for these studies in part because of this bioRxiv paper and because we failed to detect any robust intergenerational effects using P. aeruginosa PA14 in any of our assays – including at the RNA-seq level (unpublished).

   Nonetheless, we have since confirmed with Coleen Murphy’s lab that they do find P. vranovensis elicits the same transgenerational effect on behaviour as P. aeruginosa. We expect that future investigations into the conditions under which P. vranovensis elicits effects that are lost/erased after 1 generation and the conditions under which effects might be maintained for more than 3 generations will be highly interesting.

   They found 279 genes that exhibited intergenerational changes in all C species tested, but most interestingly, they show that a reversal in gene expression corresponds to a reversal in response to bacterial infection (beneficial in two species and deleterious on one). This is very intriguing! This was further supported by similar observations of osmotic stress response.

   We thank Reviewer 2 for their excitement and we agree that these findings were highly exciting.

   They also report that intergenerational effects are stress-specific and there have deleterious effects in mismatched environments, and, importantly, when worms were subject to multiple stresses. It is quite likely that offspring will experience a range of environments and that several environmental stresses will be present simultaneously in nature. I really liked this aspect of this work as I think that tests in different environments, especially environments with multiple stresses, are often lacking, which limits the generality of the conclusions.

   Another interesting piece of the puzzle is that beneficial and deleterious effects could be mediated by the same mechanisms. It would be interesting to explore this further. However, this is not a real criticism of this work. I think that the authors collected an impressive dataset already and every good study generates new research questions.

   Given these findings, I was particularly keen to see what comes of transgenerational effects. The general answer was that there aren't many, and the authors conclude that all intergenerational effects that they studied are largely reversible and that intergenerational and transgenerational effects represent distinct phenomena. While I think that this is a very important finding, I am not sure whether we can conclude that intergenerational and transgenerational effects are not related.

   In my view, an alternative interpretation is that intergenerational effects are common while transgenerational effects are rare. Because intergenerational effects are stress-specific, transgenerational effects could be stress-specific as well.

   We agree with reviewer 2 that our findings suggest that intergenerational effects are common and transgenerational effects are either rare in comparison or only occur under specific conditions. We have updated the text to include this interpretation.

   Perhaps different mechanisms regulate intergenerational responses to, say, different forms of starvation (e.g. compare opposing transgenerational responses to prolonged larval starvation (Rechavi et al. doi:10.1016/j.cell.2014.06.020) and rather short adulthood starvation (Ivimey-Cook et al. 2021 https://doi.org/10.1098/rspb.2021.0701). Perhaps some (most?) forms of starvation generate only intergenerational responses and do not generate transgenerational responses. But some do. Those forms of starvation that generate both intergenerational and transgenerational effects could do so via same mechanisms and represent the same phenomenon. I am by no means saying this is the case, but I am not sure that the absence of evidence of transgenerational effects in this study necessarily suggests that inter- and trans-generational effects are different phenomena.

   We agree and, similar to above, have updated the text accordingly to state that it is also very possible that transgenerational effects only occur under certain conditions.

   The only concern real concern was the lack of phenotypic data on F3 beyond gene expression. Ideally, I would like to see tests of pathogen avoidance and starvation resistance in F3. However, given the amount of work that went into this study, the lack of strong signature of potential transgenerational effects in gene expression, and the fact that most of these effects were shown previously to last only one generation, I do not think this is crucial.

   We thank reviewer 2 for these comments and agree that phenotypic investigations of F3 effects are also very interesting.

   We have previously investigated the phenotypic effects of all of the stresses used in this paper on F3 animals using the assays described here and consistent with our new gene expression findings we previously found that most of these stresses do not exert phenotypic effects in F3 animals (Burton et al. 2020, Willis et al 2021, Hibshman et al., 2016).

   Separately, we have also attempted to investigate the effects of pathogen exposure on pathogen avoidance, as these effects have previously been reported to occur transgenerationally, but to date have been unable to consistently replicate these findings. We expect that this is likely due to what might be subtle differences in conditions between labs (differences in water used for the media prep, air humidity, potential differences in N2 wild-type strains etc….) because assays such as behavioral avoidance are known to be very sensitive to many different environmental inputs.

   We currently believe that our experiences as they relate to intergenerational and transgenerational effects support the general conclusion of this manuscript that while intergenerational effects are common and easy to initiate across multiple labs (the intergenerational effects studied here have now been successfully reproduced in labs in the US, UK, and Canada), transgenerational effects might be more specific and/or only occur/be initiated under more stringent conditions – perhaps with the aim of avoiding the costs of such multigenerational effects.

   Future studies of exactly when/under what conditions C. elegans initiates intergenerational vs transgenerational effects is likely to be very interesting.

   It would be very interesting to compare gene expression and other phenotypic responses in F1 and F3 between P. vranovensis and PA14. Also, it would be interesting to test the adaptive value of intergenerational and transgenerational effects after exposure to both strains in different environments. This is would be very informative and help with understanding the evolutionary significance of transgenerational epigenetic inheritance of pathogen avoidance as reported previously. Why response to P. vranovensis is erased while response to PA14 is maintained for four generations? Are nematodes more likely to encounter one species than the other? Again, however, this is not something necessary for this study.

   We completely agree with Reviewer 2 and have indeed attempted these experiments both in Burton et al., 2020 and in unpublished results.

   With regards to the transgenerational F3 effects, as mentioned above, P. vranovensis has been reported to elicit the same transgenerational effect as P. aeruginosa PA14 – at least as reported in the Kaletsky et al., 2020 bioRxiv version of the manuscript from the same studies. (GRb0427 is an isolate of P. vranovensis).

   To date, however, in our laboratory we have been unable to detect any transgenerational effects for either P. vranovensis or P. aeruginosa infection on gene expression data from RNA-seq experiments (data from this manuscript and unpublished data).

   It is not yet clear why this is the case, but we note that the RNA-seq analysis from the transgenerational PA14 studies (published in Moore et al., Cell 2019) was performed on F1 animals and thus was looking at intergenerational effects – to our knowledge no RNA-seq on F3 progeny from animals exposed to PA14 has ever been published. Thus, as it stands there is no existing F3 gene expression studies done using PA14 for us to compare our results to, but it remains possible that PA14 does not elicit specific effects on F3 gene expression when analyzed by RNA-seq.

   For F1 effects we have published a gene expression comparison for P. vranovensis and P. aeruginosa F1 effects in a previous manuscript (Burton et al 2020) and will add a mention of this to the text. Briefly, we detected very few F1 effects on gene expression when exposing adults to P. aeruginosa for 24 hours and parental infection by P. aeruginosa did not result in protection for offspring from P. vranovensis infection (Burton et al., 2020). We concluded that the intergenerational adaptation to P. vranovensis was not initiated by P. aeruginosa and was at least somewhat specific to P. vranovensis as well as the new species of Pseudomonas described in this manuscript which does cross protect.

   The main strengths of this paper are i) use of multiple stresses; ii) use of multiple species; iii) tests in different environments; and iv) simultaneous evaluation of intergenerational and transgenerational responses. This study is first of a kind, and it provides several important answers, while highlighting clear paths for future work.

   Excellent work and I think it will generate a lot of interest in the community, definitely want to see it published in eLife.

   We agree with Reviewer 2 and thank them for their kind comments.

   Reviewer #3 (Public Review):

   In this manuscript, the authors address whether the mechanisms mediating intergenerational effects are conserved in evolution. This question is important not only to frame this phenomenon in an evolutionary context, but to address several interlinked questions: is there a mechanism in common between adaptive versus deleterious effects? What makes some effects last one instead of several generations? What is the ecological relevance for those mechanisms? Using Caenorhabditis elegans as a model of reference, they compare four types of intergenerational effects on additional three Caenorhabditis species.

   The authors used previously characterized models of intergenerational inheritance, focusing on those that are likely to have adaptive significance. This is relevant, because the adaptive relevance of other published examples of inter- and transgenerational inheritance is not clear. They used functional studies to probe for conservation of mechanisms for bacterial infection and resistance to osmolarity stress, which is a major strength of this study. The data supports the claim of conservation in some types of intergenerational inheritance and divergence in others. One major question addressed in this manuscript is whether there is a potential overarching mechanism that confers stress-resistance across generations. Their experiments convincingly show that this is not the case, but that instead, there are stress-specific mechanisms responsible for intergenerational inheritance.

   We agree and thank Reviewer 3 for their kind comments.

   Read the original source
2. 

   eLife

   Jun 14, 2022

   Evaluation Summary:

   The authors study intergenerational adaptation patterns in four relatively closely related nematode species, using previously established experimental procedures. Phenotypic and transcriptomic data are used to compare responses to stress triggers in the offspring generation between the species. The authors conclude that at least some of the responses are evolutionary conserved.

   (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

   Read the original source
3. 

   eLife

   Jun 14, 2022

   Reviewer #1 (Public Review):

   The general idea of comparing response patterns to stress in the offspring generation is new and very interesting. However, the data that are presented are in several ways preliminary. The phenotype comparisons are mostly convincing, although statistical treatments are partly unclear, given that each "replicate" includes itself many individuals. The transcriptomic data are minimal (only three replicates) and lack comparison to the stress responses in the parental animals. The analysis of the transcriptome data is limited to counting overlaps between significantly changed genes, without deeper discussion of the genes and pathways that are affected. The top response genes that are directly tested have been discovered before. Hence, while interesting patterns are evident from the data, this work largely …

   Reviewer #1 (Public Review):

   The general idea of comparing response patterns to stress in the offspring generation is new and very interesting. However, the data that are presented are in several ways preliminary. The phenotype comparisons are mostly convincing, although statistical treatments are partly unclear, given that each "replicate" includes itself many individuals. The transcriptomic data are minimal (only three replicates) and lack comparison to the stress responses in the parental animals. The analysis of the transcriptome data is limited to counting overlaps between significantly changed genes, without deeper discussion of the genes and pathways that are affected. The top response genes that are directly tested have been discovered before. Hence, while interesting patterns are evident from the data, this work largely confirms prior work, including that described in Burton et al. 2020.

   Read the original source
4. 

   eLife

   Jun 14, 2022

   Reviewer #2 (Public Review):

   Transgenerational effects (TE) (usually defined as multigenerational effects lasting for at least three generations) generated a lot of interest in recent years but the adaptive value of such effects is unclear. In order to understand the scope for adaptive TE we need to understand i) whether such effects are common; ii) whether they are stress-specific; and iii) if there are trade-offs with respect to performance in different environments. The last point is particularly important because F1, F2 and F3 descendants may encounter very different environments. On the other hand, intergenerational effects (lasting for one or two generations) are relatively common and can play an important role in evolutionary processes. However, we do not know whether intergenerational and transgenerational effects have same …

   Reviewer #2 (Public Review):

   Transgenerational effects (TE) (usually defined as multigenerational effects lasting for at least three generations) generated a lot of interest in recent years but the adaptive value of such effects is unclear. In order to understand the scope for adaptive TE we need to understand i) whether such effects are common; ii) whether they are stress-specific; and iii) if there are trade-offs with respect to performance in different environments. The last point is particularly important because F1, F2 and F3 descendants may encounter very different environments. On the other hand, intergenerational effects (lasting for one or two generations) are relatively common and can play an important role in evolutionary processes. However, we do not know whether intergenerational and transgenerational effects have same underlying mechanisms.

   This study makes a big step towards resolving these questions and strongly advances our understanding of both phenomena. Much of the previous work on mechanisms of multigenerational effects has been conducted in C. elegans and this works uses the same approach. They focus on bacterial infection, Microsporidia infection, larval starvation and osmotic stress. I did not quite understand why the authors chose to focus on P. vranovensis rather than P. aeruginosa P14 that has been used in previous studies of transgenerational effects in C. elegans. However, this is a minor point because I guess they were interested in broad transgenerational responses to bacterial infection rather than in strain-specific ones. The authors used different Caenorhabditis species, which is another strength of this study in addition to using multiple stresses.

   They found 279 genes that exhibited intergenerational changes in all C species tested, but most interestingly, they show that a reversal in gene expression corresponds to a reversal in response to bacterial infection (beneficial in two species and deleterious on one). This is very intriguing! This was further supported by similar observations of osmotic stress response.

   They also report that intergenerational effects are stress-specific and there have deleterious effects in mismatched environments, and, importantly, when worms were subject to multiple stresses. It is quite likely that offspring will experience a range of environments and that several environmental stresses will be present simultaneously in nature. I really liked this aspect of this work as I think that tests in different environments, especially environments with multiple stresses, are often lacking, which limits the generality of the conclusions.

   Another interesting piece of the puzzle is that beneficial and deleterious effects could be mediated by the same mechanisms. It would be interesting to explore this further. However, this is not a real criticism of this work. I think that the authors collected an impressive dataset already and every good study generates new research questions.

   Given these findings, I was particularly keen to see what comes of transgenerational effects. The general answer was that there aren't many, and the authors conclude that all intergenerational effects that they studied are largely reversible and that intergenerational and transgenerational effects represent distinct phenomena. While I think that this is a very important finding, I am not sure whether we can conclude that intergenerational and transgenerational effects are not related.

   In my view, an alternative interpretation is that intergenerational effects are common while transgenerational effects are rare. Because intergenerational effects are stress-specific, transgenerational effects could be stress-specific as well.

   Perhaps different mechanisms regulate intergenerational responses to, say, different forms of starvation (e.g. compare opposing transgenerational responses to prolonged larval starvation (Rechavi et al. doi:10.1016/j.cell.2014.06.020) and rather short adulthood starvation (Ivimey-Cook et al. 2021 https://doi.org/10.1098/rspb.2021.0701). Perhaps some (most?) forms of starvation generate only intergenerational responses and do not generate transgenerational responses. But some do. Those forms of starvation that generate both intergenerational and transgenerational effects could do so via same mechanisms and represent the same phenomenon. I am by no means saying this is the case, but I am not sure that the absence of evidence of transgenerational effects in this study necessarily suggests that inter- and trans-generational effects are different phenomena.

   The only concern real concern was the lack of phenotypic data on F3 beyond gene expression. Ideally, I would like to see tests of pathogen avoidance and starvation resistance in F3. However, given the amount of work that went into this study, the lack of strong signature of potential transgenerational effects in gene expression, and the fact that most of these effects were shown previously to last only one generation, I do not think this is crucial.

   It would be very interesting to compare gene expression and other phenotypic responses in F1 and F3 between P. vranovensis and PA14. Also, it would be interesting to test the adaptive value of intergenerational and transgenerational effects after exposure to both strains in different environments. This is would be very informative and help with understanding the evolutionary significance of transgenerational epigenetic inheritance of pathogen avoidance as reported previously. Why response to P. vranovensis is erased while response to PA14 is maintained for four generations? Are nematodes more likely to encounter one species than the other? Again, however, this is not something necessary for this study.

   The main strengths of this paper are i) use of multiple stresses; ii) use of multiple species; iii) tests in different environments; and iv) simultaneous evaluation of intergenerational and transgenerational responses. This study is first of a kind, and it provides several important answers, while highlighting clear paths for future work. Excellent work and I think it will generate a lot of interest in the community.

   Read the original source
5. 

   eLife

   Jun 14, 2022

   Reviewer #3 (Public Review):

   In this manuscript, the authors address whether the mechanisms mediating intergenerational effects are conserved in evolution. This question is important not only to frame this phenomenon in an evolutionary context, but to address several interlinked questions: is there a mechanism in common between adaptive versus deleterious effects? What makes some effects last one instead of several generations? What is the ecological relevance for those mechanisms? Using Caenorhabditis elegans as a model of reference, they compare four types of intergenerational effects on additional three Caenorhabditis species.

   The authors used previously characterized models of intergenerational inheritance, focusing on those that are likely to have adaptive significance. This is relevant, because the adaptive relevance of other …

   Reviewer #3 (Public Review):

   In this manuscript, the authors address whether the mechanisms mediating intergenerational effects are conserved in evolution. This question is important not only to frame this phenomenon in an evolutionary context, but to address several interlinked questions: is there a mechanism in common between adaptive versus deleterious effects? What makes some effects last one instead of several generations? What is the ecological relevance for those mechanisms? Using Caenorhabditis elegans as a model of reference, they compare four types of intergenerational effects on additional three Caenorhabditis species.

   The authors used previously characterized models of intergenerational inheritance, focusing on those that are likely to have adaptive significance. This is relevant, because the adaptive relevance of other published examples of inter- and transgenerational inheritance is not clear. They used functional studies to probe for conservation of mechanisms for bacterial infection and resistance to osmolarity stress, which is a major strength of this study. The data supports the claim of conservation in some types of intergenerational inheritance and divergence in others. One major question addressed in this manuscript is whether there is a potential overarching mechanism that confers stress-resistance across generations. Their experiments convincingly show that this is not the case, but that instead, there are stress-specific mechanisms responsible for intergenerational inheritance.

   Read the original source
6. 

   Version published to 10.7554/elife.73425 on eLife

   Oct 8, 2021
7. 

   Version published to 10.1101/2021.05.07.443118v1 on bioRxiv

   May 8, 2021