The preprint presents a population genomics study of mate preferences suspected to be implied reinforcement. The authors studied the correlation between SNPs/genes and the presence or absence of mate preference leading to reproductive isolation with a closely related subspecies (Choosy vs Non choosy). The authors identify olfactory receptors genes that may implied in reinforcements. Those genes mainly clusters in two areas in the genome.

Reinforcement is an important mechanism because it may be involved in speciation and explain why there is so many species. However we lack of empirical data to determine the prevalence of this mechanism in natural populations. I then think this study has value because it investigates the genetic basis of mate preference suspected to be implied reinforcement. However I am not an expert on genomics, so I cannot judge the pertinence of the method used in this preprint.

My main concern about this study is that the authors did not study the correlation between the genotype and the mating behavior but between the genotype and the locality. If I understood well the study, the mating behavior was inferred from individual locally and not properly tested. This method may underestimate the variability of mating preference between individuals of a same locality.

Another concern is about the meaning of the C2 statistic. Much of the study is based on this statistic. However I did not understand how it is computed. At least it would be nice to have an idea of what it represents.

Also the authors did not explain the relatedness observed in figure 1b. I am surprised by this relatedness as it did not correspond to the spatial structure. It would be nice if the authors discuss about this.

I also have minor comments:

l27: what is a functional prediction ?
l30-31: ‘which contrasts allele frequencies’ it may be because I am unfamiliar with genomics technique but I don’t understand what it means
l50: ‘to understand how behavioural traits evolve’ it is a bit vague, what do you mean ? To identify the mechanisms underlying behaviors ?
l52: maybe replace ‘play’ but ‘may play’ is more correct, see Servedio 2004 the what and why of research on reinforcement.
l62: why these cases are ‘relatively simple’ ?
l63: similarly what are ‘more complex traits’ ? Do you mean that the genetic basis implied a larger number of genes ?
l66: similarly what is a ‘complex behavioral trait’ ? Does that mean what there are simple behavioral trait ?
l166-168: ‘a situation that makes the identification of outlier divergent loci in the Focal Test comparing Choosy and Non-Choosy populations conservative.’ Can you explain in few words why ?
l212: I don’t understand what are ‘already known variants’
l512-516: this part is unclear for me. I do not understand why it would correspond to a matching rule.

This paper investigated the genetic basis of an olfactory-based behavioral divergence in the model organism Mum musculus. To do this, this study compared populations with choosy vs. non-choosy behavior, while also contrasting populations with the same behavior as a control. To further establish the link between genetic divergence and phenotypic divergence, the study also examines divergence across all annotated genes.  Moreover, this study also examines possible genomic signature of reinforcement, including selection sweeps among genetic differentiation outliers, and association between outlier genes and candidate hybrid sterility regions. I think this is a well-designed, well-executed, extensive research. The intro and discussion are well-written and make extensive connection to relevant literatures in the field. It is an important contribution to the methodology of uncovering genetic basis of behaviors, which is notoriously hard in natural systems. It serves as a rare study that examined genomic signature of reinforcement. I only have a few minor suggestions:

1.     The exact comparisons in Focal vs. control test in Figure 1 C is not clear. My take is that Focal test means comparing choosy 1 vs. Non choosy 1; choosy 1 vs. Non-choosy 2; choosy 2 vs. Non choosy 1; choosy 2 vs. non-choosy 2 , and that Control test is choosy 1 vs. choosy 2; Non-choosy 1 vs. Non-choosy 2.  However, in the figure C, “vesus” symbol is used to show the comparisons, but it means different things in different tests. I suggest to write down each comparison in the figure legend and the result session.

2.     Line 295-306. the title of the section states no signatures of selective sweeps confuses me. In the text, there are some genes showed selective sweeps in both Choosy populations.

3.     Figure 4. I am a bit overwhelmed by different font sizes and different colors of genes in the figure. I understand different color means different functional receptors. However, what do different sizes font mean? The symbol “<”, “>” means where the gene starts and ends? No annotations of these symbol meanings are found in the figure legend.

4.     Because the key findings in this study is built upon program BAYPASS to tease apart the effect of population structure on signals of genetic divergence related to choosy behavior, I hope there is a bit more mechanistic explanation about how this program corrects for the population structure in the introduction. Right now, this information is buried in the method section.

This is a very nice study and I have enjoyed and learnt while reading it. The goal of the study is to
find the genetic basis of olfactory-based mating preferences in mice. For that purpose, the authors sampled and sequenced individuals from the border of a hybrid zone, where strong assortment occurs, and from other locations away from the border of this zone, where no assortment has been identified.
By splitting and contrasting individuals into choosy (from the border of the hybrid zone) and non-choosy,
the authors obtain candidate regions and genes and then do functional analyses where they identify multiple olfactory and vomeronasal receptor genes as outliers.

Overall, I do think the goals are clearly stated, the paper is well written, and the methods are appropiate
and well used.

I really enjoyed the discussion, although the section on the role of receptor genes seemed a bit long. I believe a bit more insight into what sort of analyses can be done in the future, especially for those readers
not familiar with the work of Isogai et al (2011), would be useful to close down the manuscript.

Some issues I have:

It seems there is no reduced diversity in the outlier regions, and no signs of selective sweeps,
and all analyses are indicative of polygenic selection. That seems to be the case both for outlier genes
in C2_max or in C2_mean, while I would have expected some different in diversity on those two scenarios.
On the whole, I would appreciate whether some findings, like no reduced diversity and no overlap with
candidate hybrid sterility genes were expected or unexpected, or what could be the explanation
for either of these findings.

Are there simulations to know which scenarios of selection / genetic architecture result in outliers
of C2_max and which in outliers of C2_mean?

Minor comments:
- I suppose the order of methods at the end corresponds to the authors' final choice of journal, but
I personally find it easier to follow when methods are described prior to results.
- l. 215 and l. 221: coding consequences?
- The sentence finishing in l. 270 should be rewritten ("were less found in the very most significantly")
- l. 749: with -> which

In Fig. 3, the three clusters could be magnified to better appreciate the structure.
In Supp. Fig.1, text size is too small.