Peer review of: Balancing selection via life-history trade-offs maintains an inversion polymorphism in a (2019)

Reviewers' comments: 

Reviewer #1 (Remarks to the Author): 

This very nice paper explores the maintenance of a chromosomal inversion polymorphism in the 
seaweed fly Coelopa frigida. The authors use a combination of experimental evolution and computer 
simulations to understand how the polymorphism is maintained. They show, through impressive 
experiments and exhaustive combinations of simulated parameters, that the polymorphism can be 
maintained under a wide range of scenarios, but most likely involving antagonistic pleiotropy between 
reproductive success and survival (mediated through variation in development time). The degree of 
environmental heterogeneity, density and sex-specific selection may all also play important roles in 
determining whether the polymorphism is stable and what the equilibrium frequencies of the different 
haplotypes are. Under many scenarios antagonistic pleiotropy leads to overdominance of fitness. 
The polymorphism has been extensively studied since the early-mid 1980s, principally by Butlin and 
colleagues. Thus the observation that this polymorphism can be maintained by heterozygote 
advantage is not completely new. Where this study is really impressive though is that (i) the 
experiments where repeated across 4 replicates, which showed very consistent patterns and (ii) the 
simulations really do show how a very diverse set of scenarios (which are sensibly and experimentally 
parameterised) can lead to antagonistic pleiotropy and the persistence of the polymorphism. I feel for 
these reasons the paper is lifted beyond an incremental advance of our understanding of this 
particular system to something of far more general and applicable relevance to evolutionary genetic 
research. 
I do not have any major criticisms of the work – I found it to be well written, convincing, and very 
carefully planned. I have a few minor comments that I hope the authors might consider when revising 
it, but they should be easy to address. 

1) I think it would be useful to provide a bit more background to the polymorphism, especially if any 
genomics work has been done on it. What size is it (both in Mbp and as a proportion of the genome)? 
Do we know how many genes reside within it? This sort of information would help the reader evaluate 
some of the discussion about genetic loads etc. 

2) Lines 204-207. Isn’t a decreased excess of αα homozygotes inevitable as the frequency of α goes 
up? As the frequency of α increases, so does the expected number of homozygotes. Therefore, it 
becomes mathematically harder for the observed number of αα homozygotes to exceed the expected 
number. Negative-frequency dependence may not be required to explain the data (consistent with 
Table S8 / line 240). 

3) It is my understanding that in the simulations, the duration of available habitat is an independent 
random draw for each individual. However, in the real world this independence is almost certain to be 
violated. For example, an exceptionally high tide that sweeps away seaweed will affect many 
individuals simultaneously. As I understand it, that non-independence is not built into the simulations 
and I wonder whether it should be? (or at least discussed). 

Some minor typos / editorial suggestions. 
Line 151 – replace ‘origin of’ with ‘original’ 
Line 219 – replace ‘male sire a disproportionate’ with ‘males sire a disproportionately’ 
Line 224 – replace ‘build’ with ‘built’ 
Line 257-258 – replace ‘slow-developing males to reach adulthood’ with ‘slow-developing males from 
reaching adulthood’ 
Line 265 – ‘as observed IN many natural populations’ 
Line 652 – ‘Genic’, not ‘genie’. Mistake seems to be on the Heredity webpage, but not the pdf. 

Reviewer #2: 

[Note from the editor] This reviewer provided all their comments confidentially to the editor; they 
made several suggestions which I paraphrase here: 

1) The main results are rather similar to previous work, including (for example) Butlin, Day et al. 
Some additional context, to more fully explain how this relates to previous work and where the 
novelty lies, would be welcome. 

2) The results are discursive and lack statistical support in the text. To clarify journal policy, we do ask 
that full methods and all the main results are reported in the main manuscript rather than SI. 

3) The discussion is long but repetitive. The results and main implications are clear and easily 
summarised; the authors should talk more about selection via male success and how this affects the 
maintenance of the polymorphism.