Genomic insights into Yak (Bos grunniens) adaptations for nutrient assimilation in high-altitudes

Abstract

High-altitude environments present formidable challenges for survival and reproduction, with organisms facing limited oxygen availability and scarce nutrient resources. The yak (Bos grunniens), indigenous to the Tibetan Plateau, has notably adapted to these extreme conditions. This study delves into the genomic basis of the yak's adaptation, focusing on the positive selection acting on genes involved in nutrient assimilation pathways. Employing techniques in comparative genomics and molecular evolutionary analyses, we selected genes in the yak that show signs of positive selection associated with nutrient metabolism, absorption, and transport. Our findings reveal specific genetic adaptations related to nutrient metabolism in harsh climatic conditions. Notably, genes involved in energy metabolism, oxygen transport, and thermoregulation exhibited signs of positive selection, suggesting their crucial role in the yak's successful colonization of high-altitude regions. The study also sheds light on the yak's immune system adaptations, emphasizing genes involved in response to various stresses prevalent at elevated altitudes. Insights into the yak's genomic makeup provide valuable information for understanding the broader implications of high-altitude adaptations in mammalian evolution. They may contribute to efforts in enhancing livestock resilience to environmental challenges.

Keywords: Evolutionary mechanisms; High-altitude adaptation; Nutrient assimilation; Positive selection; Yak genomics.

Figure 1

Domain architecture and selection analysis of the yak CAMK2B protein. This figure, created with the DOG 1.0 illustrator, showcases the domain structure of the CAMK2B protein and emphasizes the analysis of its conserved domains. Special attention is given to the protein kinase domain, where sites under positive selection have been identified. These sites are mapped onto the three-dimensional structure of the yak CAMK2B protein, revealing the adaptive evolution at the molecular level. The Selecton analysis is visualized through a color-coded scheme, where sequences are compared against aligned nucleotide coding sequences to infer selection pressures. Codons under positive selection are highlighted in yellow and brown, indicating adaptive changes. Codons under neutral selection are marked in grey and white, signifying evolutionary neutrality, and codons under purifying selection are in purple, denoting the removal of deleterious mutations. This color coding allows for an at-a-glance understanding of the selective forces acting on the CAMK2B protein.

Figure 2

Domain structure analysis of the yak glul protein. Illustrated using the DOG 1.0 illustrator, this figure represents the molecular structure of the GLUL protein and its functional domains, with a focus on the analysis of conserved domains. Notably, sites of positive selection have been identified within the ATP binding domain. The three-dimensional structure of the yak GLUL protein has been annotated to indicate positively selected amino acid sites derived from Selecton analysis. The figure employs a color-coding scheme to represent the type of selection pressure on codons: yellow and brown for positive selection, suggesting adaptive evolutionary changes; grey and white for neutral selection, indicating evolutionary stasis; and purple for purifying selection, where detrimental variations are selectively eliminated. This color-coding facilitates a visual distinction between the different selection pressures across the protein's structure.

Figure 3

Cumulative distribution of the likelihood ratio test for the BUSTED test broken down by the contributions of individual sites.

Figure 4

Phylogenetic analysis of synonymous and non-synonymous variant ratios in yak CAMK2B and GLUL genes.. This figure presents a phylogenetic analysis of the CAMK2B and GLUL genes in the yak, focusing on the ratio of synonymous (silent) to non-synonymous (amino acid-altering) variants. Displayed on a logarithmic scale, the plot provides an estimated distribution of these ratios as inferred from the gene alignment. Each ellipse approximates the Gaussian variance around the rate estimates, with the color gradient representing the density of posterior samples within the distribution for each rate estimate. Points located above the diagonal line indicate positive selection (ω > 1), suggesting adaptive evolutionary changes. In contrast, points below the line signify negative or purifying selection (ω < 1), indicating the removal of disadvantageous variants. The diagonal line itself represents the threshold of neutral evolution (ω = 1), where the rates of synonymous and non-synonymous variants are equal, implying no selection pressure.

Figure 5

Genetic recombination of Yak genes showing evolutionary breakpoints in the genome. Left: the algorithm's maximum breakpoint location for each number of breakpoints considered. Right: the log scale c-AIC score rises between successive breakpoint values. Support for breakpoint placement based on an average model length of the entire tree by partition.

Figure 6

The clustering of amino acid residues that interact with one another. The structure of various ligand-binding residues is shown on the left, and the clustering of amino acids according to the physicochemical properties of ligand-interacting residues is shown on the right.

Figure 7

Analysis of protein–protein interactions in nutritional pathways. This figure visualizes the network of protein–protein interactions among proteins involved in the yak's nutritional pathways. The nodes, represented by circles, correspond to proteins; green nodes are proteins with well-characterized functions, while red nodes indicate proteins whose functions have not been fully elucidated. The black lines, or edges, connecting the nodes represent the interactions between proteins. The length of each line suggests the relative interaction distance or functional relationship strength between the proteins—shorter lines imply a closer or more direct interaction. This network provides insights into the complex interplay of proteins that govern nutritional processes, highlighting both known and potentially novel interactions that contribute to the yak's high-altitude adaptability.

Figure 8

Tissue-specific expression patterns of nutritional pathway genes in yak. This figure displays the differential expression of genes involved in the yak's nutritional pathways across a range of tissue types, with data sourced from the GTEx consortium. The graphical representation illustrates the relative expression levels of these genes, highlighting tissues where each gene is most actively transcribed. This tissue-specific expression profile provides insights into the functional roles of these genes in different biological processes and systems within the yak. Understanding these patterns is essential for elucidating the genetic mechanisms that enable yaks to adapt and thrive in the demanding high-altitude environments where they reside.