Magnus Nordborg Reviewing Editor; Austrian Academy of Sciences, Austria Diethard Tautz Senior Editor; Max-Planck Institute for Evolutionary Biology, Germany Magnus Nordborg Reviewer; Austrian Academy of Sciences, Austria Kristin Tessmar Reviewer; University of Vienna, Austria In the interests of transparency, eLife includes the editorial decision letter and accompanying author responses. A lightly edited version of the letter sent to the authors after peer review is shown, indicating the most substantive concerns; minor comments are not usually included.

Thank you for submitting your article "Decoupled maternal and zygotic genetic effects shape the evolution of development" for consideration by eLife. Your article has been reviewed by three peer reviewers, including Magnus Nordborg as the Reviewing Editor and Reviewer #1, and the evaluation has been overseen by Diethard Tautz as the Senior Editor. The following individual involved in review of your submission has agreed to reveal their identity: Kristin Tessmar (Reviewer #2).

The reviewers have discussed the reviews with one another and the Reviewing Editor has drafted this decision to help you prepare a revised submission.

Summary:

This paper investigates the genetics of a major life-history dimorphism – development via a morphologically distinct larval form vs. direct development – in a marine worm. Rather than "super-genes" determining life-history strategy, separate genetic loci with different modes of inheritance were found to influence egg size and larval morphology.

This is a substantial and well-written contribution addressing a biological question of broad interest.

Essential revisions:

There were two major issues that could lead to over-interpretation of the results. First, fitness effects are implied but not measured, and this is not always clear from the writing. A hypothetical fitness landscape is shown in Figure 1B, and it is clearly stated in the figure legend that this landscape is hypothetical. However, at several other points in the text, sentences are worded in a way that implies that fitness may have actually been measured, rather than inferred based on direction of phenotypic effects. This could be fixed by more cautious phrasing. For example:

In Abstract, original text: "The fitness of zygotic alleles depends upon their maternal background, creating a positive frequency-dependence that may homogenize local populations."

More conservative wording: "The likely fitness effects of zygotic alleles depends upon their maternal background, creating a positive frequency-dependence that may homogenize local populations."

Even more conservative wording: "The phenotypic effects of zygotic alleles on a hypothetical fitness landscape depends upon their maternal background, creating a positive frequency-dependence that may homogenize local populations."

In the Discussion, original text: "We identified six chromosomes with large effects for four traits, implying that S. benedicti populations can segregate 729 possible genotypic combinations, most of which are maladaptive."

More conservative wording: "We identified six chromosomes with large effects for four traits, implying that S. benedicti populations can segregate 729 possible genotypic combinations, most of which would produce combinations of intermediate phenotypes that are likely to be maladaptive."

In the Discussion, original text: "Finally, we found that the evolutionary transition to lecithotropic development requires the interaction of two genotypes, the mother and offspring. The fitness of a zygotic allele depends on the probability it occurs in a favorable maternal genetic background"

More conservative: "Finally, we found that the evolutionary transition to lecithotropic development requires the interaction of two genotypes, the mother and offspring. Because of this dual control of larval phenotype, the likely fitness effects of a zygotic allele depends on whether it occurs in a favorable maternal genetic background." etc.

The second point is more difficult to address. Due to failed genotyping, the genotypes of the P0 grandparents of the existing cross, or the F1 parents used to make F2s, are not known. Thus the direction of the allelic effects in the cross is actually not known, although the paper is generally written as if they went in the expected direction (again, the information is in the paper, but it is very easy to miss on a first reading). This is not a trivial point, and it affects the conclusions of the paper. For example, the difficulty contrasting alleles would have invading different genetic backgrounds is less of an issue if existing planktotrophic and lecithotropic populations already harbor lots of alleles with non-concordant phenotypic effects.

This issue could be addressed by carrying out additional genotyping to try to confirm whether the planktotrophic and lecithotropic alleles segregating in the cross do in fact come from either the planktotropic and lecithotropic grand parental populations. Note that the additional genotype calls would only be in the regions harboring key QTLs, rather than on a whole genome basis. With a focused genotyping effort, it may be possible to determine these key genotypes on limited or poor quality material still available from the original grandparents. Alternatively, it may be possible to infer the likely grandparental genotypes in the key QTL regions, based on the differential frequency of linked markers found in additional individuals sampled from the starting populations.

If you cannot produce these data, a thorough rewrite will be required to make sure all claims are supported, and the manuscript will be reviewed again.

Less substantially, please clarify in what sense Figure 4 shows maternal "masking", and in general improve description, i.e. clearly label what exactly is the offspring of one cross, how many individuals were scored for each chaetae number.…