Integrated Peptidogenomics Decoding Yak Non-Conventional Peptides: Functional Mapping and Biopotential Mining of Genetic Resources.

Objective: Non-conventional peptides, have been found to play a key role in basic plant and animal biological processes. This study aims to investigate from the perspective of NCPs to reveal the adaptive molecular genetic mechanisms of yaks.

Methods: We established an integrated peptidogenomic pipeline, constructed a customized six-frame translation database using high-throughput mass spectrometry, and applied it to the large-scale identification of NCPs in several vital organs/tissues of yaks.

Results: Compared to conventional peptides, these NCPs exhibit unique properties derived from introns, UTRs, out-of-frame exons, and intergenic regions. Additionally, our findings indicate that translation events are more prevalent in unannotated transcripts than previously believed. Combined with transcriptome analysis and ribosome mapping analysis, 727 NCPs were determined to be derived from lncRNA and 944 NCPs were determined to be derived from circRNA. Interestingly, the number of hydrophobic amino acids in NCPs was found to be higher than that of hydrophilic amino acids in almost all tissues; whereas for CPs the results were reversed. These findings suggest their potential involvement in maintaining protein stability and combating oxidative stress. Furthermore, the in vitro antioxidant activity of the 38 candidate peptides further confirmed their physiological functions; however, specific physiological mechanisms require further investigation.

Conclusion: In conclusion, this study demonstrates that a substantial portion of the yak genome can be translated into molecules with biological functions which is highly significant for functional genome research, and these unique hidden molecules will provide basic data for future biomedical development and plateau disease treatment.