Domestication pressures and the rise of livestock spliceopathies

Alternative splicing drives molecular diversity, yet livestock spliceopathies remain underrecognised despite their major economic impact. By synthesising evidence across major livestock species, we reveal how splicing defects disrupt production through recurrent patterns: splice variants in dosage-sensitive genes affect growth and fertility, breed-specific splice-regulatory changes drive disease susceptibility, and epigenetic modifications enable environmental adaptation. These patterns reflect evolutionary constraints and domestication pressures driving aberrant splicing in modern breeds. Recent technological advances enable systematic investigation and treatment: long-read sequencing uncovers hidden splicing complexity, while clustered regularly interspaced short palindromic repeats (CRISPR) and antisense oligonucleotides offer precision interventions. However, critical gaps persist in functional validation and population-scale mapping. Addressing these within the One Health framework will advance animal welfare, food security, and comparative medicine, positioning alternative splicing as a fundamental driver of phenotypic diversity.