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Genomics, proteomics & bioinformatics2025; 23(3); qzaf025; doi: 10.1093/gpbjnl/qzaf025

LCORL and STC2 Variants Increase Body Size and Growth Rate in Cattle and Other Animals.

Abstract: Natural variants can significantly improve growth traits in livestock and serve as safe targets for gene editing, thus being applied in animal molecular design breeding. However, such safe and large-effect mutations are severely lacking. Using ancestral recombination graphs, we investigated recent selection signatures in beef cattle breeds, pinpointing sweep-driving variants in the LCORL and STC2 loci with notable effects on body size and growth rate. The ACT-to-A frameshift mutation in LCORL occurs mainly in central-European cattle, and stimulates growth. Remarkably, convergent truncating mutations were also found in commercial breeds of sheep, goats, pigs, horses, dogs, rabbits, and chickens. In the STC2 gene, we identified a missense mutation (A60P) located within the conserved region across vertebrates. We validated the two natural mutations in gene-edited mouse models, where both variants in homozygous carriers significantly increase the average weight by 11%. Our findings provide insights into a seemingly recurring gene target of body size enhancing truncating mutations across domesticated species, and offer valuable targets for gene editing-based breeding in animals.
© The Author(s) 2025. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.
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Publication Date: 2025-03-17 PubMed ID: 40094447PubMed Central: PMC12448305DOI: 10.1093/gpbjnl/qzaf025Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study identifies natural genetic variants in LCORL and STC2 genes that significantly increase body size and growth rate in cattle and several other domesticated animals.
  • The researchers validated these growth-enhancing mutations using gene-edited mice, highlighting their potential for improving livestock breeding through precise genetic methods.

Background

  • Growth traits like body size and growth rate are important for livestock productivity.
  • Natural genetic variants that robustly enhance these traits are rare but valuable as safe targets for gene editing.
  • Animal molecular design breeding uses such genomic information to accelerate improvement in traits without introducing foreign DNA.

Research Approach

  • The researchers used ancestral recombination graphs, a method to detect recent selection signatures in genomes across populations, focusing on beef cattle breeds.
  • They aimed to uncover specific genetic mutations under strong recent positive selection that drive desirable growth traits.

Key Findings in Cattle

  • Two loci, LCORL and STC2, were identified with variants under strong selection associated with body size and growth rate.
  • In the LCORL gene, an ACT-to-A frameshift mutation was found primarily in central-European cattle. This mutation presumably disrupts the normal protein but results in enhanced growth phenotypes.
  • For the STC2 gene, a missense mutation (amino acid substitution A60P) was identified within a conserved region across vertebrates, indicating its functional importance.

Cross-Species Convergence

  • The LCORL gene exhibited convergent truncating mutations (mutations leading to protein truncation) in commercial breeds across many domesticated species including sheep, goats, pigs, horses, dogs, rabbits, and chickens.
  • This convergence suggests a common, evolutionarily favored mechanism where disrupting or truncating LCORL enhances body size or growth rate in various animals.

Functional Validation Using Gene-Edited Mice

  • The team created gene-edited mouse models carrying the natural cattle variants in LCORL and STC2 genes.
  • Homozygous carriers of either variant exhibited an approximately 11% increase in average body weight compared to controls.
  • This provided direct experimental evidence that these specific mutations causally enhance growth.

Significance of the Study

  • Identifies novel, naturally occurring mutations with large beneficial effects on livestock growth that can be safely utilized in breeding programs.
  • Highlights a recurring target gene (LCORL) where truncating mutations increase body size across a broad range of domesticated animals, pointing to common genetic mechanisms.
  • The findings open opportunities for precise gene editing to improve economically important growth traits in animal agriculture without introducing exogenous genes.
  • Contributes to fundamental understanding of vertebrate growth regulation and evolutionary adaptation during domestication.

Implications for Animal Breeding

  • Offers clear gene editing targets (LCORL and STC2 variants) to enhance cattle growth rates and body size safely and effectively.
  • Because similar mutations appear beneficial in multiple species, these targets may be translated across species in molecular breeding efforts.
  • Improved growth traits can increase meat production efficiency, contributing to better resource utilization and economic gains.

Conclusion

  • This research advances the application of genomics and gene editing in livestock by revealing natural high-impact mutations modulating growth.
  • It underscores the potential of leveraging evolutionary-selected variants for molecular design breeding, improving animal production sustainably and predictably.

Cite This Article

APA
Bai F, Cai Y, Qiu M, Liang C, Pan L, Liu Y, Feng Y, Cao X, Yang Q, Ren G, Jiao S, Gao S, Lu M, Wang X, Heller R, Lenstra JA, Jiang Y. (2025). LCORL and STC2 Variants Increase Body Size and Growth Rate in Cattle and Other Animals. Genomics Proteomics Bioinformatics, 23(3), qzaf025. https://doi.org/10.1093/gpbjnl/qzaf025

Publication

Genomics, proteomics & bioinformatics
ISSN: 2210-3244
NlmUniqueID: 101197608
Country: England
Language: English
Volume: 23
Issue: 3
PII: qzaf025

Researcher Affiliations

Bai, Fengting
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Cai, Yudong
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Qiu, Min
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Liang, Chen
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Pan, Linqian
  • College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Liu, Yayi
  • College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Feng, Yanshuai
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Cao, Xuesha
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Yang, Qimeng
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Ren, Gang
  • College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Jiao, Shaohua
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Gao, Siqi
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Lu, Meixuan
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Wang, Xihong
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Heller, Rasmus
  • Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
Lenstra, Johannes A
  • Faculty of Veterinary Medicine, Utrecht University, 3584 CM, Utrecht, The Netherlands.
Jiang, Yu
  • Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.

MeSH Terms

  • Animals
  • Cattle / growth & development
  • Cattle / genetics
  • Body Size / genetics
  • Mice
  • Mutation, Missense
  • Breeding
  • Frameshift Mutation
  • Intercellular Signaling Peptides and Proteins / genetics

Conflict of Interest Statement

Yu Jiang, Yudong Cai, Fengting Bai, Min Qiu, Chen Liang, and Yanshuai Feng are inventors on two patent applications related to this work submitted on 27 December 2024 by Northwest A&F University (Patent Application Nos. 202411951967.8 and 202411951964.4). The other authors declare that they have no competing interests.

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