Yunsheng Zhang

Host DNA methylation plays a crucial role in antiviral defense, yet its impact on viral susceptibility remains unclear. Using ducklings resistant (R) or susceptible (S) to duck hepatitis A virus type 3 (DHAV-3), we integrated whole-genome bisulfite and oxidative bisulfite sequencing with transcriptomics. We observed a distinct intragenic 5-methylcytosine (5mC) signature between the two lines, with endocytic pathway genes being hypomethylated in susceptible, while hypermethylated in resistant ducklings. Critically, the genebody 5mC level displayed a dominant negative correlation with gene expression, and functionally determined viral entry efficiency. Following infection, the methylation program further coordinated post-entry host responses, including immune, fatty acid metabolism, and autophagy pathways. This genebody methylation signature defines a regulatory framework governing DHAV-3 susceptibility, offering insights for antiviral strategies and disease-resistance breeding. IMPORTANCE: Duck hepatitis A virus type 3 (DHAV-3) causes severe mortality in ducklings, leading to substantial economic losses in poultry production. Understanding why some ducks resist infection while others succumb is critical for developing sustainable control strategies. Here, we discovered that a chemical “tag” on DNA—called methylation—acts as a natural switch that determines susceptibility. Resistant ducks carry higher methylation on genes controlling viral entry, effectively closing the door to the virus. Susceptible ducks lack this protective methylation, allowing viral access. Experimentally manipulating this switch directly altered infection efficiency, proving methylation is a functional controller of disease outcome. Our findings reveal that epigenetic variation, independent of genetic sequence, shapes host vulnerability. This opens new possibilities for breeding virus-resistant poultry through epigenetic markers, reducing reliance on vaccines and antiviral drugs. The work also provides a framework for understanding how animals defend against viral pathogens at the molecular level.

Background: Feed efficiency (FE) is a major determinant of productivity, economic sustainability, and environmental impact in livestock production. Although Pekin ducks constitute a substantial proportion of global poultry meat production, improvement of FE has progressed slowly, largely due to an incomplete understanding of its complex biological basis. In particular, how host genomic variation and gut microbial communities—especially across different intestinal segments—jointly contribute to FE remains poorly characterized in ducks. Results: We integrated whole-genome sequencing (WGS) with segment-resolved microbiota profiles from 313 Pekin ducks to delineate host–microbiota architecture underlying feed conversion ratio (FCR), which exhibited moderate heritability ( h ² =0.23, P _LRT = 2.53 × 10 ^–2 ). Genome-wide association study (GWAS) identified two major genomic regions involving two genes ALG13 and TRPC5 , which implicated in appetite regulation and energy balance to impact FE. Meanwhile, gut microbial communities exhibited spatial heterogeneity along the intestinal tract, with host genetics-associated taxa such as Solobacterium (cecum) and Eubacterium_eligens_group (jejunum) negatively correlating with FCR, likely via enhanced short-chain fatty acid production and improved energy harvest. Variation partitioning revealed that host genetics explained the largest FCR variance (36.96%), followed by cecal microbiota. Conclusions: Our results highlight coordinated host–microbiota interactions influencing FE, offering targets for breeding and microbiota-based interventions.

Background: As a major economic trait in poultry, egg production efficiency attracts widespread interest in breeding and production. However, limited information is available about the underlying genetic architecture of egg production traits in ducks. In this paper, we analyzed six egg production-related traits in 352 F ₂ ducks derived from reciprocal crosses between mallard and Pekin ducks. Results: Feed conversation ratio (FCR) was positively correlated with feed intake but negatively correlated with egg-related traits, including egg weight and egg production, both phenotypically and genetically. Estimates of pedigree-based heritability were higher than 0.2 for all traits investigated, except hip-width. Based on whole-genome sequencing data, we conducted genome-wide association studies to identify genomic regions associated with these traits. In total, 11 genomic regions were associated with FCR. No genomic regions were identified as significantly associated with hip-width, total feed intake, average daily feed intake, and total egg production. Analysis of selective sweeps between mallard and Pekin ducks confirmed three of these genomic regions on chromosomes 13, 3 and 6. Within these three regions, variants in candidate genes that were in linkage disequilibrium with the GWAS leader single nucleotide polymorphisms (SNPs) (Chr13:2,196,728, P = 7.05 × 10 ^–14 ; Chr3:76,991,524, P = 1.06 × 10 ^–12 ; Chr6:20,356,803, P = 1.14 × 10 ^–10 ) were detected. Thus, we identified 31 potential candidate genes associated with FCR, among which the strongest candidates are those that are highly expressed in tissues involved in reproduction and nervous system functions of ducks: CNTN4 , CRBR , GPR63 , KLHL32 , FHL5 , TRNT1 , MANEA , NDUFAF4 , and SCD . Conclusions: For the first time, we report the identification of genomic regions that are associated with FCR in ducks and our results illustrate the genomic changes that occurred during their domestication and are involved in egg production efficiency.