The adaptive architecture is shaped by population ancestry and not by selection regime

  1. Kathrin A. Otte
  2. Viola Nolte
  3. François Mallard
  4. Christian Schlötterer

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Abstract

Understanding the genetic architecture of adaptive phenotypes is a key question in evolutionary biology. One particularly promising approach is Evolve and Resequence (E&R), which combines advantages of experimental evolution such as time series, replicate populations and controlled environmental conditions, with whole genome sequencing. The recent analysis of replicate populations from two different Drosophila simulans founder populations, which were adapting to the same novel hot environment, uncovered very different architectures - either many selection targets with large heterogeneity among replicates or fewer selection targets with a consistent response among replicates. Here, we exposed the founder population from Portugal to a cold temperature regime. Although almost no selection targets were shared between the hot and cold selection regime, the adaptive architecture was similar: we identified a moderate number of loci under strong selection (19 selected alleles, mean selection coefficient = 0.072) and very parallel responses in the cold evolved replicates. This similarity across different environments indicates that the adaptive architecture depends more on the ancestry of the founder population than the specific selection regime. These observations have a pronounced impact on our understanding of adaptation in natural populations.

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    ##Author Response

    We thank the editors for considering our manuscript for publication in eLife and the reviewers for their work. However, we would like to discuss several of their comments.

    The key issue seems to be a lack of novelty of our work, which is not correct in our opinion.

    We would like to quickly reiterate why we think that our findings are novel and have very broad implications.

    The importance of polygenic adaptation is becoming increasingly clear. Unfortunately, it is widely assumed that polygenic adaptation is very difficult, if not impossible, to study in natural populations, because the associated allele frequency shifts are too small to be experimentally characterized (Pritchard et al., 2010). Hence, typically the collective response of many loci are considered, which frequently results in wrong results due to population stratification (Berg et al., 2019; Sohail et al., 2019).

    Therefore, we have used experimental evolution to characterize polygenic adaptation. Experimental evolution is widely recognized as a powerful tool because of the possibility to replicate experiments. Here, we expand the power of experimental evolution by an hitherto unrecognized aspect: the impact of linkage disequilibrium - we demonstrate that two founder populations with different levels of linkage disequilibrium (LD) result in entirely different selection responses. The consequence of different LD structures is shown by our observation that the same population (i.e. identical LD structure) evolving in two different environments shows the same selection response, but a different population with different LD structure in the same environment shows different selection responses.

    This result has important implications for all studies of polygenic adaptation in natural populations because LD is not accounted for in studies of polygenic adaptation, but like in our study, haplotype blocks with multiple loci could result in a strongly selected allele. Hence, LD will determine the likelihood of this to occur. Furthermore, accounting for linkage provides the opportunity to study polygenic adaptation also in natural populations - a substantial change to the current testing paradigms.

    The second key result of our study is that we demonstrate that selection in hot and cold environments does not fit the simple model of polygenic adaptation, where the same set of loci is responding in different directions, when opposing selection regimes are applied. As pointed out by reviewer #2, this is particularly important as it shows that current models of polygenic adaptation are not well-suited to understand adaptation imposed by contrasting ecological factors. We show that there is almost no overlap between the haplotype blocks selected in the hot and cold environment. Most importantly, this is not a matter of power as we show that the blocks responding in one selection regime are not changing their frequency in the opposite direction in the other selection regime. We anticipate that this insight will have a profound impact on theoretical models of polygenic adaptation. Furthermore, as we studied temperature adaptation, our results will have also important consequences for the battery of ongoing studies aiming to link selection signatures to response to climate change.

    In brief, we think that very minor clarifications in our manuscript can solve the technical issues identified by the reviewers and will provide a clearer picture about the general implications of our findings.

    A detailed response to the comments of the reviewers is given below.

    ###Reviewer #1:

    Otte et al. used an evolve and re-sequence strategy to explore "the genetic architecture of adaptive phenotypes". The authors previously found different genetic architectures across different founder populations evolving in a common hot environment. The authors chose one of these founder populations for replicated experimental evolution (5 replicate populations) in a cold environment for 50 generations. The authors were surprised to discover the same number of loci evolve under strong selection between the hot-evolved and cold-evolved replicate populations, though the 20-ish loci are largely non-overlapping. The distribution of selection coefficients was also similar. They interpret this commonality as evidence that the founder population history has a larger effect on adaptive architecture than the selection regime.

    The study demonstrates a comprehensive effort to discover the number of genome regions and distribution of selection coefficients that emerge from a highly controlled experimental evolution project. The experienced team applies a sophisticated toolkit to this powerful experimental design - a toolkit that grows ever more sophisticated with each new experimental run that they perform. However, the authors set me up to learn why such different adaptive architectures emerge from different founder populations. Ultimately, the researchers acknowledge that they "cannot pinpoint the cause for the differences in the inferred adaptive architecture..."

    Here, the reviewer correctly identified one of the main new questions that arose from the new experiment we performed in this study. In a large part of the discussion and the associated analyses we are providing answers to this question, i.e. possible alternative explanations for the different observed architectures in the Portugal vs. the Florida population. We can indeed not pinpoint "the" cause for the differences that the reviewer seems to request here as a definite answer, but we favour one of the explanations that has not yet been discussed in literature previously (LD).

    Some results simply recapitulated the previous Portugal E&R study and other results recapitulated a D. melanogaster E&R study.

    This statement about "some results" is ignoring the main new experiment of this study, which is the Portugal population evolving in a cold temperature. For this, we carried out a new selection experiment in a new environment, which finds different selection targets than the previously published experiments. This new experiment therefore does not recapitulate the previous results. We then compare this new experiment to a previous one, and this comparison raises a set of new questions that we address in this manuscript. Only for the purpose of making that comparison, we indeed "simply recapitulated" "some results" of the previous study. The statement is therefore misleading in the way it is put here. Furthermore, the D. melanogaster study is also not recapitulated: in that study, it was not possible to identify selected haplotypes. The D. melanogaster study was therefore unable to determine how many selection targets were shared between the hot and cold selection regimes. The identification of selected haplotypes was a major improvement in this study, which made it possible only now to determine how many targets are shared and to evaluate whether selection targets behave as predicted by the trait optimum model.

    I did not find the "common adaptive architecture" across different selection regimes to be a particularly compelling discovery of sufficiently broad interest.

    This is a very subjective opinion and it would be good if the reviewer had explained why this is no interesting discovery to her/him. We feel that this statement simply reflects that the reviewer does not fully appreciate the complexity of polygenic adaptation. We would like to point out again, that this result has important implications for the interpretation of selection signatures in natural populations.

    Other concerns and questions can be found below:

    Major concerns:

    1. Pg. 4: It is my understanding that the power of multiple populations from a single founder evolving in parallel allows for more rigorous identification of loci targeted by selection. I found it surprising to discover that if a lack of replication emerges from an experimental evolution study, this outcome is interpreted as "genetic redundancy." First, genetic redundancy has a precise definition in genetics that muddles the author's meaning. And second this interpretation seems rather post-hoc.

    This statement shows that the reviewer is disregarding the work of Barghi et al (2019, PLoS Biology) and the definition of redundancy in the context of polygenic adaptation as discussed by Laruson et al. (2020) or Barghi et al 2020 (Nature Reviews Genetics). In any case, this is a semantic issue and should not be considered as a major issue with our manuscript.

    1. To "shed more light on the different selection responses" is a weak motivation. The introduction sets me up to understand why selection responses are so different but no major insights into the "why" emerge from the cold-adaptation experiment.

    We modestly disagree - we clearly discuss different explanations of “why” and favor one of them (LD)

    1. More explanation of figure 1 in the main text is needed. Does each point correspond to a SNP that consistently changes across all five populations? Or is this the union?

    The reviewer does not seem to be familiar with the statistical analyses that have been used in our study in the same way as it is common practice in the field. Despite the common use of this test, we still provided a detailed explanation in M&M and explicitly mentioned the test in the figure legend. But this can easily be detailed even further and should not be a major issue with this manuscript.

    1. Line 210: How did the researchers define "stress" and determine that the degree of stress is equivalent across two temperature regimes? The absence of these data undermine the potency of the comparison.

    It is not clear why the reviewer requires a more elaborate definition of temperature stress - the concept of extreme temperatures imposing stress is well established and we cite the relevant literature for Drosophila in the text. Furthermore, it is not apparent why the reviewer requests the degree of stress to be equivalent between the two temperature regimes.

    1. How can the authors be sure that the only difference between the hot and cold populations was temperature? Was competition/population size/etc held constant? Might the lack of overlap between hot and cold adapted loci stem from one such regime selecting for a different phenotype? (i.e., not temperature tolerance)

    As clearly stated in M&M, the culture conditions were the same with the exception of temperature.

    1. Line 237: The authors assert that most alleles show a temperature-specific response - a discovery with precedent in the literature, including from this team of researchers. The authors attribute the absence of common loci between temperature regimes to the high number of generations (50) compared to the number across seasons cited in Bergland et al. The researcher could easily look for common targets at earlier time points of experimental evolution to test this idea.

    This is an interesting suggestion, but the reviewer fails to explain why the analysis of early generations should be more informative than the analysis of later generations. Several studies have already documented the opposite.

    1. Line 292-293: This section reads as disingenuous - the researchers could have explored overlap between Portugal and Florida founders using only the selected loci coordinates and look for non-random overlap using simulations/resampling tests.

    The reviewer seems to assume that we could easily apply the same test for overlap that we used for the hot vs. cold comparison within the Portugal population to the Portugal hot vs. Florida hot comparison. But this is not feasible, and we clearly explain why the comparison of selected haplotype blocks between different founder populations is not helpful (low LD results in different haplotype blocks - even with the same target)

    1. Discussion: The speculation about why such different architectures emerged across Portugal and Florida was diluted by the absence of initial fitness estimation upon subjection to a cold environment (which would have offered evidence for different initial "optima" across founder populations) as well as the change in fitness from generation 0 to generation 50.

    It is not apparent why the reviewer requests a fitness estimate at the cold environment. Our analysis only included a single population in the cold environment. Hence, the only informative comparison is the one in the hot environment which has been done for both populations and is referenced in the manuscript.

    1. The simulations and corresponding discussion would make for an interesting review/opinion piece but not as new results for this manuscript.

    Unlike the reviewer, we think that a good discussion puts the results into perspective with different hypotheses on how to explain it and link this to the current literature.

    Minor Comments:

    1. Pg. 3. The recurrent citation of Barghi et al. in the Introduction undermined the reader's impression that fundamental questions are being addressed in this article.

    Maybe it escaped the reviewer’s attention that we cited three different Barghi et al. papers and only one reports experimental data (cited only once), while the others are required to describe the theoretical framework, including the concept of "redundancy" which the reviewer misunderstood. New fundamental questions in this current manuscript are addressed using the Portugal population, which was selected in a cold temperature regime (not hot-evolved Florida, which was the topic of Barghi et al. 2019).

    1. Lines 33-39: The argument that parallel signatures of selection across distinct natural populations are insufficient to address the polygenic basis of adaptive phenotypes, and so comparatively more contrived E&R studies are required, was unconvincing.

    Unfortunately, the reviewer does not provide support for this strong statement. In fact, we find the statement of “contrived E&R studies” not as objective as we would have liked to see in a scientific discourse.

    1. Line 158: Confusing. Should "among" actually be "within"?

    The reviewer is not right - the correct wording is "among" not within: multiple different haplotypes can carry the actual target of selection, and they can differ by additional variants which themselves are not selected for. Multiple haplotypes with the selection target are also experiencing more pronounced frequency changes than expected under neutrality. The correlation of their allele frequency trajectories depends, however, on the extent that hitchhiking SNPs are shared among these haplotypes. To account for this, we used a less stringent correlation cutoff.

    1. Line 486: I believe that the authors would be hard-pressed to find in the literature a paper declaring that "single population...[is] sufficient to understand the genetic basis of adaptive traits".

    In fact, many selection tests are targeting only a single population and most studies only apply them to a single population.

    ###Reviewer #2:

    This reviewer mainly asks us to discuss some of his/her ideas - this can be done, but since reviewer#1 felt already that there is too much discussion in our manuscript this is a bit of a mixed message.

    Overall Review: This is another commendable study from the Schloterer lab that features next generation genome-wide sequencing of multiple evolving populations. It compares results obtained with two different selection regimes, one hot and one cold, and two different founding populations of Drosophila simulans, one from Portugal and one from Florida. The results reveal a lack of consistency among selection regimes and founding populations. Temperature-dependent adaptation is shown to be "local" or "contingent," rather than globally consistent. My chief recommendations concern the experimental and theoretical contexts within which this study should be interpreted.

    Major points:

    1. I do not require any additional data collection or statistical revision. My comments are organized in terms of experimental paradigm (A) and theoretical significance (B).

    A.

    1. The typical paradigm for experimental evolution in this and many other labs is the use of hybrid populations created from isofemale lines. This method for founding experimental populations can be expected to generate some degree of random "historicity" as the isofemale lines approach fixation of specific genotypes with high stochasticity. Then there are further stochastic and historical effects which arise when such lines are hybridized. The strengths and limitations of this paradigm should be addressed. Most importantly, such stochastic historical effects might be the source of the discrepancy between the replicate lines derived from Portugal and Florida.

    We would like to emphasize that we were using freshly established isofemale lines kept in the laboratory for at most 10 generations, as stated in the M&M section.

    1. As the authors themselves point out, there is a comparative difficulty arising from the different scales of replication used for the Florida versus Portugal experiments.

    The reviewer is correct, and since we were aware of this, we performed statistical tests to account for this.

    A further question for large-scale experimentation is whether a larger and uniform level of replication might produce more similar results, such as 20 evolving populations from each source. Or indeed, three sets of ten evolving populations from three distinct founders from the two sources, with a total of 60 evolving experimental lineages. The authors should discuss whether they believe that their findings would hold up with such an expanded experimental protocol.

    This is an interesting thought of its own, but we feel that it does not contribute much to our current study.

    1. The authors themselves point out at one point that their experiments might have benefitted from some phenotypic characterization of the presumed temperature adaptation. That raises the more general question of how the field of experimental evolution can progress with some labs just doing phenotypes and other labs just doing genome-wide sequencing. Surely this and other studies would be strengthened by combining the two types of assay. Furthermore, genomic evolution might be usefully analyzed in terms of the degree to which specific genomic changes can be associated with specific phenotypic changes, as that is the foundation for adaptation itself.

    We would like to draw the attention to the fact that we performed a laboratory natural selection experiment, for which the environmental factor is known, but not the actually selected phenotype - hence the phenotyping is not as trivial as implied by the reviewer.

    B.

    1. This is yet another study that finds difficulties with the invocation of noroptimal selection along a one-dimensional functional gradient. Such models have been long-standing favorites of evolutionary theorists, such as Kimura and Lande. But that preference may arise more from the ease with which these models can be formulated and analyzed by theoreticians. Actual evolving populations don't seem to embody the precepts of such theory, whether the issue is the maintenance of genetic variation (see the work of Turelli, for example) or the evolution of closely studied populations, as illustrated by this study. An alternative point of view that the authors should discuss is that such models are indeed NOT usually correct.

    It is very interesting that this reviewer feels that our data demonstrate that the prevailing model of polygenic adaptation is wrong, but our manuscript is still considered to be of insufficient novelty.

    1. There are alternative theoretical frameworks that address the maintenance of genetic variation and the response to selection. Among these are schemes of protected polymorphism arising from overdominance, epistasis, and frequency-dependent selection. If the thrust of the preceding point 4 is accepted, then it would be theoretically salient for the authors to suggest what type of underlying population genetic machinery would best account for their findings, in place of the noroptimal selection-mutation balance model.

    We thank the reviewer for these interesting suggestions. However, their predictions are not at all trivial to test. For this reason, generations of population geneticists tried to test them, so we feel that this task is well beyond the scope of this manuscript.

    ###Reviewer #3:

    In their manuscript 'The adaptive architecture is shaped by population ancestry and not by selection regime,' Otte and colleagues use an evolve and resequence strategy to examine the response of a Portugal population of D. simulans responds to cold temperature. The authors identify putative targets of selection and compare the number of targets, their location, and the distribution of selection coefficients to previous work on the same population exposed to hot temperatures as well as a different population exposed to hot temperatures. The topic is of general interest, the work is sound and the writing is clear and concise.

    1. It is not clear what the novel contribution of this manuscript is. The title indicates that the key finding is that population of origin mediates response to selection rather than the selection regime. However, the authors fail to provide compelling data to support that. The data are from 1 population under two selection regimes and a second population under one of those regimes. There simply aren't enough comparisons to infer that population ancestry plays a bigger role than selection regime in adaptive evolution.

    We disagree with the reviewer and would like to repeat the logic of our experiment:

    Comparison 1: contrast of different populations in the same environment -> different architecture

    Comparison 2: contrast of the same population in different environments -> same architecture

    With this simple design it is possible to reach the conclusion that the architecture is affected by population history more than by selection regime and no more populations are needed to reach this conclusion. This insight has not been reported before.

    1. The authors also seem to argue that a contribution of this paper is that it illustrates that temperature adaptation is not a single trait. This was the major finding of a 2014 paper from the same group in D. melanogaster- a single founder population was exposed to hot and cold temperatures and the authors found almost no overlap between the putatively selected variants in the two different temperature regimes.

    We would like to point out that the analysis of Tobler et al. (2014) is on the basis of individual SNPs, which is difficult to interpret because of the many segregating inversions in D. melanogaster. All the complications of these data and the implications for the interpretation can be found in the discussion of Tobler et al. (2014). In the current study, we are identifying selected haplotype blocks, which is mandatory to compare the architectures and selection responses.

    1. Beyond the limited impact of the current work, there are some additional specific issues. The authors note that it was 'remarkable' that the distribution of selection coefficients and the number of inferred selection targets between the hot and cold experiments was 'highly similar.' What is the null expectation? Where does the null come from?

    This is a minor semantic issue. Naturally, there is no null model for the number of selection targets, but if two populations selected for the same trait provide different architectures, different selection regimes should be even more likely to generate different architectures.

    1. The discussion is somewhat unsatisfying and largely speculative. The 'different trait optima' section reads as straw man; this could be reframed to better guide the reader.

    Naturally, the discussion intends to put the results in a broader context. It would have been helpful to read how s/he envisions a reframing that would improve the manuscript.

    There is little support for the 'differences in adaptive variation' hypothesis.

    It would have been helpful to read which kind of support the reviewer would have expected beyond the evidence we have already provided.

    The section on LD was interesting, but the simulation findings should reside in the results section.

    This could be easily moved, but we feel that it is well-placed in the discussion as we use the simulations to compensate for the lack of literature on this field (again demonstrating the novelty of our manuscript).

    References:

    Barghi, N., R. Tobler, V. Nolte, A. M. Jakšić, F. Mallard, K. A. Otte, M. Dolezal, T. Taus, R. Kofler, & C. Schlötterer (2019). Genetic redundancy fuels polygenic adaptation in Drosophila. PLOS Biology 17: e3000128.

    Barghi, N., J. Hermisson, & C. Schlötterer (2020). Polygenic adaptation: a unifying framework to understand positive selection. Nature Reviews Genetics . Berg, J.J., Harpak, A., Sinnott-Armstrong, N., Joergensen, A.M., Mostafavi, H., Field, Y., Boyle, E.A., Zhang, X., Racimo, F., Pritchard, J.K., et al. (2019). Reduced signal for polygenic adaptation of height in UK Biobank. Elife 8.

    Bergland, A. O., E. L. Behrman, K. R. O’Brien, P. S. Schmidt, & D. A. Petrov (2014). Genomic Evidence of Rapid and Stable Adaptive Oscillations over Seasonal Time Scales in Drosophila. PLoS Genetics 10, e1004775.

    Láruson, Á. J., S. Yeaman, & K. E. Lotterhos (2020). The Importance of Genetic Redundancy in Evolution. Trends in Ecology and Evolution 35: 809–822. Pritchard, J.K., Pickrell, J.K., and Coop, G. (2010). The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Current biology : CB 20, R208-215.

    Sohail, M., Maier, R.M., Ganna, A., Bloemendal, A., Martin, A.R., Turchin, M.C., Chiang, C.W., Hirschhorn, J., Daly, M.J., Patterson, N., et al. (2019). Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies. Elife 8.

  2. eLife

    ###Reviewer #3:

    In their manuscript 'The adaptive architecture is shaped by population ancestry and not by selection regime,' Otte and colleagues use an evolve and resequence strategy to examine the response of a Portugal population of D. simulans responds to cold temperature. The authors identify putative targets of selection and compare the number of targets, their location, and the distribution of selection coefficients to previous work on the same population exposed to hot temperatures as well as a different population exposed to hot temperatures. The topic is of general interest, the work is sound and the writing is clear and concise.

    1. It is not clear what the novel contribution of this manuscript is. The title indicates that the key finding is that population of origin mediates response to selection rather than the selection regime. However, the authors fail to provide compelling data to support that. The data are from 1 population under two selection regimes and a second population under one of those regimes. There simply aren't enough comparisons to infer that population ancestry plays a bigger role than selection regime in adaptive evolution.

    2. The authors also seem to argue that a contribution of this paper is that it illustrates that temperature adaptation is not a single trait. This was the major finding of a 2014 paper from the same group in D. melanogaster- a single founder population was exposed to hot and cold temperatures and the authors found almost no overlap between the putatively selected variants in the two different temperature regimes.

    3. Beyond the limited impact of the current work, there are some additional specific issues. The authors note that it was 'remarkable' that the distribution of selection coefficients and the number of inferred selection targets between the hot and cold experiments was 'highly similar.' What is the null expectation? Where does the null come from?

    4. The discussion is somewhat unsatisfying and largely speculative. The 'different trait optima' section reads as straw man; this could be reframed to better guide the reader. There is little support for the 'differences in adaptive variation' hypothesis. The section on LD was interesting, but the simulation findings should reside in the results section.

  3. eLife

    ###Reviewer #2:

    Overall Review: This is another commendable study from the Schloterer lab that features next generation genome-wide sequencing of multiple evolving populations. It compares results obtained with two different selection regimes, one hot and one cold, and two different founding populations of Drosophila simulans, one from Portugal and one from Florida. The results reveal a lack of consistency among selection regimes and founding populations. Temperature-dependent adaptation is shown to be "local" or "contingent," rather than globally consistent. My chief recommendations concern the experimental and theoretical contexts within which this study should be interpreted.

    Major points:

    1. I do not require any additional data collection or statistical revision. My comments are organized in terms of experimental paradigm (A) and theoretical significance (B).

    A.

    1. The typical paradigm for experimental evolution in this and many other labs is the use of hybrid populations created from isofemale lines. This method for founding experimental populations can be expected to generate some degree of random "historicity" as the isofemale lines approach fixation of specific genotypes with high stochasticity. Then there are further stochastic and historical effects which arise when such lines are hybridized. The strengths and limitations of this paradigm should be addressed. Most importantly, such stochastic historical effects might be the source of the discrepancy between the replicate lines derived from Portugal and Florida.

    2. As the authors themselves point out, there is a comparative difficulty arising from the different scales of replication used for the Florida versus Portugal experiments. A further question for large-scale experimentation is whether a larger and uniform level of replication might produce more similar results, such as 20 evolving populations from each source. Or indeed, three sets of ten evolving populations from three distinct founders from the two sources, with a total of 60 evolving experimental lineages. The authors should discuss whether they believe that their findings would hold up with such an expanded experimental protocol.

    3. The authors themselves point out at one point that their experiments might have benefitted from some phenotypic characterization of the presumed temperature adaptation. That raises the more general question of how the field of experimental evolution can progress with some labs just doing phenotypes and other labs just doing genome-wide sequencing. Surely this and other studies would be strengthened by combining the two types of assay. Furthermore, genomic evolution might be usefully analyzed in terms of the degree to which specific genomic changes can be associated with specific phenotypic changes, as that is the foundation for adaptation itself.

    B.

    1. This is yet another study that finds difficulties with the invocation of noroptimal selection along a one-dimensional functional gradient. Such models have been long-standing favorites of evolutionary theorists, such as Kimura and Lande. But that preference may arise more from the ease with which these models can be formulated and analyzed by theoreticians. Actual evolving populations don't seem to embody the precepts of such theory, whether the issue is the maintenance of genetic variation (see the work of Turelli, for example) or the evolution of closely studied populations, as illustrated by this study. An alternative point of view that the authors should discuss is that such models are indeed NOT usually correct.

    2. There are alternative theoretical frameworks that address the maintenance of genetic variation and the response to selection. Among these are schemes of protected polymorphism arising from overdominance, epistasis, and frequency-dependent selection. If the thrust of the preceding point 4 is accepted, then it would be theoretically salient for the authors to suggest what type of underlying population genetic machinery would best account for their findings, in place of the noroptimal selection-mutation balance model.

  4. eLife

    ###Reviewer #1:

    Otte et al. used an evolve and re-sequence strategy to explore "the genetic architecture of adaptive phenotypes". The authors previously found different genetic architectures across different founder populations evolving in a common hot environment. The authors chose one of these founder populations for replicated experimental evolution (5 replicate populations) in a cold environment for 50 generations. The authors were surprised to discover the same number of loci evolve under strong selection between the hot-evolved and cold-evolved replicate populations, though the 20-ish loci are largely non-overlapping. The distribution of selection coefficients was also similar. They interpret this commonality as evidence that the founder population history has a larger effect on adaptive architecture than the selection regime.

    The study demonstrates a comprehensive effort to discover the number of genome regions and distribution of selection coefficients that emerge from a highly controlled experimental evolution project. The experienced team applies a sophisticated toolkit to this powerful experimental design - a toolkit that grows ever more sophisticated with each new experimental run that they perform. However, the authors set me up to learn why such different adaptive architectures emerge from different founder populations. Ultimately, the researchers acknowledge that they "cannot pinpoint the cause for the differences in the inferred adaptive architecture..." Some results simply recapitulated the previous Portugal E&R study and other results recapitulated a D. melanogaster E&R study. I did not find the "common adaptive architecture" across different selection regimes to be a particularly compelling discovery of sufficiently broad interest. Other concerns and questions can be found below:

    Major concerns:

    1. Pg. 4: It is my understanding that the power of multiple populations from a single founder evolving in parallel allows for more rigorous identification of loci targeted by selection. I found it surprising to discover that if a lack of replication emerges from an experimental evolution study, this outcome is interpreted as "genetic redundancy." First, genetic redundancy has a precise definition in genetics that muddles the author's meaning. And second this interpretation seems rather post-hoc.

    2. To "shed more light on the different selection responses" is a weak motivation. The introduction sets me up to understand why selection responses are so different but no major insights into the "why" emerge from the cold-adaptation experiment.

    3. More explanation of figure 1 in the main text is needed. Does each point correspond to a SNP that consistently changes across all five populations? Or is this the union?

    4. Line 210: How did the researchers define "stress" and determine that the degree of stress is equivalent across two temperature regimes? The absence of these data undermine the potency of the comparison.

    5. How can the authors be sure that the only difference between the hot and cold populations was temperature? Was competition/population size/etc held constant? Might the lack of overlap between hot and cold adapted loci stem from one such regime selecting for a different phenotype? (i.e., not temperature tolerance)

    6. Line 237: The authors assert that most alleles show a temperature-specific response - a discovery with precedent in the literature, including from this team of researchers. The authors attribute the absence of common loci between temperature regimes to the high number of generations (50) compared to the number across seasons cited in Bergland et al. The researcher could easily look for common targets at earlier time points of experimental evolution to test this idea.

    7. Line 292-293: This section reads as disingenuous - the researchers could have explored overlap between Portugal and Florida founders using only the selected loci coordinates and look for non-random overlap using simulations/resampling tests.

    8. Discussion: The speculation about why such different architectures emerged across Portugal and Florida was diluted by the absence of initial fitness estimation upon subjection to a cold environment (which would have offered evidence for different initial "optima" across founder populations) as well as the change in fitness from generation 0 to generation 50.

    9. The simulations and corresponding discussion would make for an interesting review/opinion piece but not as new results for this manuscript.

    Minor Comments:

    1. Pg. 3. The recurrent citation of Barghi et al. in the Introduction undermined the reader's impression that fundamental questions are being addressed in this article

    2. Lines 33-39: The argument that parallel signatures of selection across distinct natural populations are insufficient to address the polygenic basis of adaptive phenotypes, and so comparatively more contrived E&R studies are required, was unconvincing.

    3. Line 158: Confusing. Should "among" actually be "within"?

    4. Line 486: I believe that the authors would be hard-pressed to find in the literature a paper declaring that "single population...[is] sufficient to understand the genetic basis of adaptive traits".

  5. eLife

    ##Preprint Review

    This preprint was reviewed using eLife’s Preprint Review service, which provides public peer reviews of manuscripts posted on bioRxiv for the benefit of the authors, readers, potential readers, and others interested in our assessment of the work. This review applies only to version 2 of the manuscript.

    ###Summary:

    The reviewers agreed that the study was well-executed and offered important insight into how decisions around experimental set up affect the outcome of experimental evolution studies. Ultimately, however, there was consensus that the results failed to support the broadest conclusion that ancestry is more important than selection regime. Moreover, given previously published reports on experimental evolution from your group and others, the current study lacked sufficient novelty.

  6. Version published to 10.1101/2020.06.25.170878v2 on bioRxiv
  7. Version published to 10.1101/2020.06.25.170878v1 on bioRxiv