General comments

This paper reports the de novo sequencing and analysis of the Wuzhishan pig (WZSP), a useful, inbred biomedical and agricultural model organism. Whilst in general the analysis has been well carried out, there are some aspects of this paper that must be improved.

Major Compulsory Revisions

1. The analysis of heterozygosis in this inbred line leaves something to be desired. The authors compare the heterozygosis of the WZSP to the naked mole rat and the human genomes. This comparison is flawed and should have included another inbred genome, such as an inbred mouse genome. Figure 1 should be redone to include an inbred mouse genome, and the results discussed in the analysis. The current conclusions reached based on the reported comparisons are not informative for the following reasons.

2. Heterozygosis in inbred animals will be a function of the number of generations of inbreeding and can be predicted to some degree by calculating the inbreeding coefficient for the animal that was sequenced. The authors should compare the observed heterozygosis to the inbreeding coefficient to determine if the reported heterozygosis is at odds with expectation.

3. During inbreeding, the theory of junctions predicts that recombination will cause regions to remain homozygous or become heterozygous. Without discussion of the length of the heterozygous regions and their relationship to known or suspected recombination hotspots we cannot decide if the observed heterozygous regions are the result of selection or recombination driven. Recombination hot and cold spots can be estimated by comparing the pig linkage map to the assembled pig genome.

Without the above information, we are therefore unable to conclude anything from the 1000 most heterozygous genes in the absence of their genomic locations correlated with recombination rates.

1. The estimate for genome size is 2.5Gbp based on kmer spectrum/frequency, yet the assembly is 2.6Gbp long. Is this discrepancy significant or within the margin of error? If it is significant, what are the likely causes? Specifically could allelic segmental duplications/CNV be responsible? This manuscript contains no analysis of segmental duplications. The manuscript should be revised to include SD results and analysis.

Minor Essential Revisions

There are a few word omissions/language problems that should be fixed:

• p.6 of the PDF, line 24 ...slightly higher than in human... should read ...than in THE human...

• p.7, line 1, outbreed should be outbred

• p.8, line 2, ...was located in CDS... should be ...WERE located in CDS...

• last line, ...were well represented in... should be ...were well represented in THE...

• p.14, line 9, ...information from the drugbank... should be ...information from drugbank...

• p.16, line 6, ...heterozygosis decreased or maintained... should be ... heterozygosis decreased or WAS maintained....

Discretionary Revisions

NONE

Level of interest: An article of outstanding merit and interest in its field

Quality of written English: Acceptable

Statistical review: No, the manuscript does not need to be seen by a statistician.

Declaration of competing interests: I declare that I have no competing interests

Major Compulsory Revisions.

None at this stage. Previous revisions have been addressed in a satisfactory fashion.

Minor/Discretionary Revisions.

None.

Level of interest: An article of outstanding merit and interest in its field

Quality of written English: Acceptable

Statistical review: Yes, and I have assessed the statistics in my report.

Declaration of competing interests: I declare that i have no competing interests.