Identification of Body Size Determination Related Candidate Genes in Domestic Pig Using Genome-Wide Selection Signal Analysis

Round 1

Reviewer 1 Report

This study is of potential interest but the paper provides insufficient details on the data and the statistical methods used to allow careful assessment of the validity of the methods and interpretation of results. Specifically, more details are needed on how the pigs included in the analysis were chosen and what the know historical background of the breeds included is, specifically differences in selection histories. Statistical methods need to be described in much greater detail: how was the Fst and ratio statistics and their associated p-values computed? How were enrichment analyses conducted? How were significance thresholds set?

In results, it is unclear how strong the evidence for selection signatures is. For example, you report that "235,623 autosomal windows were obtained. The thresholds of the top 1% selective signal windows were defined as 0.48 (FST) and 0.31 (π ratio) (Figure 1), respectively. A total of 187 CGs were identified from 280 interacted windows.". What was the 1% based on? In methods you refer to a p<0.05 threshold. Is the number of 280 interacted windows out of 235,623 more than expected by chance? Need to do multiple-test correction.

Interpretation of the enrichment analyses is also not clear.

English writing can use some improvement. E.g. use genome-wide rather than wide-genome  and selection signal instead of signal selection.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

In this genome-wide analysis the authors add upon the existing literature on the determinants of body size selection in pigs. This is an important area of study given the wide use of pigs in various fields. 

Specific points to address:

1) Page 2, Para 1: At present, a large number of genes related to body-size development have been verified, such as HMGA2, BMP2, FGFR3, and insulin-like growth factor (IGF)-1R. [19, 20].

This point can be further expanded in terms of the metabolic pathways they belong to while linking the same in the discussion where the genes identified in the study have been described. 

2) English formatting error: Page 3, Para 1: such as PI3K-Akt signaling pathway、Collecting duct acid secretion、Arginine biosynthesis, etc.

Change the comma after pathway and secretion. 

3) English grammar error: Page 3, Para 1: Of that, 7 candidate genes (e.g., PDPK1, STAT6 and ASS1) were not only enriched into metabolic-related signaling pathways, including Thyroid hormone signaling pathway, Alanine, aspartate and glutamate metabolism, etc. which not also enriched into known cell-value-added growth

Instead if 'which not also', it should be 'but also'. 

4) Of the genes that were identified and discussed, is it possible to verify them using RT-qPCR etc by using pig RNA from small and large body pigs? That would lend more credibility to the accuracy of the GWAS study. 

Author Response

Please see the attachment.

Author Response File: Author Response.docx