Animal Molecular Breeding, 2025, Vol.15, No.1, 1-8 http://animalscipublisher.com/index.php/amb 3 3.3 Regulatory roles of epigenetics and non-coding RNAs in adaptation Epigenetic mechanisms, including RNA editing and non-coding RNAs, also play a role in adaptation to high altitudes. A-to-I and C-to-U types of RNA editing sites are variably distributed and expressed in plateau goats and affect genes involved in energy metabolism, translation, and immune response (Li et al., 2023). Multi-omics approaches have uncovered complex mRNA-miRNA-lncRNA networks that regulate ovarian function, reproductive performance, and adaptive capacity, linking reproductive traits to immune and metabolic adaptation (Lv et al., 2024). Such layers of regulation make genetic architecture of plateau adaptation complex. 3.4 Cross-species comparative analyses revealing conserved and specific adaptive mechanisms Comparative genomics of domestic mammals (e.g., goat, sheep, horse, cattle, pig, dog) is uncovering both species-specific and conserved adaptive pathways. The convergent positive selection of the EPAS1 gene in multiple high-altitude domestic mammals suggests an emergent genetic response to hypoxia (Song et al., 2016; Wu et al., 2019). However, cross-species comparisons also show that closely related species, such as goats and sheep, utilize different genetic pathways and candidate genes for local adaptation, thereby reflecting the set of evolutionary solutions to similar environmental pressures (Benjelloun et al., 2023) (Figure 1). It reflects both the universality as well as specificity of genetic adaptation to high-altitude environments. Figure 1 Patterns of allele frequencies variations for candidate variants along environmental gradients (Adopted from Benjelloun et al., 2023) Image caption: a: Examples for candidate variants related to altitude in sheep (upper charts) and rainfall seasonality in goats (lower charts). These two variables were chosen as examples. For each SNP, the variation profile of allele frequency (reduced centred values) is assigned to one of the following categories: linear variation, uniform with punctual shifts at one or both extremes of the gradient. The grey box-plots represent neutral variations of allelic frequencies for a set of random variants. b: Distribution of patterns of allele frequency variation for the different environmental variables for sheep (upper) and goats (lower). (Adopted from Benjelloun et al., 2023) 4 Functional Genomics Applications Based on CRISPR 4.1 Overview of CRISPR/Cas9 technology principles and advantages The CRISPR/Cas9 system is a powerful genome editing technique that enables targeted editing through the introduction of double-strand breaks at specific genomic sites, which are then repaired by cellular mechanisms. Its major advantages are high efficiency, versatility, ease of design, and the ability to generate both knockouts and
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