Proximal digestive tract

The proximal digestive tract includes the oral cavity, salivary glands and esophagus, which together contribute to food intake, mechanical processing, lubrication, taste perception and the transport of food towards the stomach. Although these functions are conserved across mammals, differences in feeding behaviour and dietary adaptations are reflected in the anatomy, epithelial organization and secretory functions of these tissues.

The sampled tissues include lip, oral mucosa, tongue, salivary gland and oesophagus in macaque, pig, rat and mouse. For the tissue specificity analysis, lip, oral mucosa and tongue are grouped into a single main tissue type, mouth, while salivary gland and esophagus are analysed separately. In the human RNA dataset, tongue is the only sampled tissue representing the mouth, whereas salivary gland and esophagus are available in both human and all four other species. This enables cross-species comparisons of these three main tissue types. Additional human protein detection data from immunohistochemistry (IHC) is available for oral mucosa in the HPA Tissue Resource, providing complementary information about protein expression and localization.

Figure 1. Tissue sample overview and the hierarchy of grouped tissues representing tissues of the proximal digestive tract

Comparative transcriptomics of the mammalian proximal digestive tract

The transcriptomic data is used to identify genes with elevated expression in individual tissues or groups of tissues, classified into three categories:

Tissue enriched: Genes with elevated expression in a single tissue compared with all other tissues.
Group enriched: Genes with elevated expression in a limited group of tissues compared with the remaining tissues.
Tissue enhanced: Genes with elevated expression in one or more tissues compared with the average expression across tissues (gap ratio ≥2)

Tissue specificity is evaluated at two levels: first, within each species using all available tissue types, and second, using only tissues that can be directly compared between the species and human. This distinction makes it possible to explore both tissue-specific expression within each species and the conservation of expression patterns across evolution.

The results can be explored for individual genes on the gene summary pages or searched to identify genes with specific expression patterns. To assess evolutionary conservation, pairwise overlap analysis compares each species individually with human, identifying genes that share the same tissue specificity classification in corresponding tissues and quantifying the extent of overlap between species.

Tissue	Species	Elevated	Human elevated overlap
Tissue	Species	Elevated	Complete overlap	Partial overlap
Esophagus	Macaque	132	0	59
	Mouse	112	0	35
	Rat	48	0	13
	Pig	33	0	5
Mouth	Macaque	219	n/a	n/a
	Mouse	233	n/a	n/a
	Rat	172	n/a	n/a
	Pig	151	n/a	n/a
Salivary gland	Macaque	115	23	21
	Mouse	78	11	15
	Rat	105	15	23
	Pig	89	11	16

Mouth

Lip

The lips contain skin, skeletal muscle, connective tissue and mucosal epithelium, contributing to food intake and sensory exploration. Their structure and specialization differ between species, particularly in the development of tactile hairs, muscular organization and the transition between external skin and oral mucosa. Some samples may also contain hair follicles from the external skin of the lip, which should be considered when interpreting tissue-level gene expression patterns.

Tongue

The tongue contains skeletal muscle and specialized epithelial structures involved in food manipulation, swallowing and taste perception. The distribution of lingual papillae, taste buds and keratinized epithelium differs considerably between mammals, reflecting dietary adaptations and species-specific feeding behaviour.

Oral mucosa

The oral mucosa protects the underlying tissues against mechanical stress, microorganisms and chemical exposure. The degree of epithelial keratinization varies with anatomical location and species, particularly in relation to feeding behaviour and the mechanical properties of the diet.

Species coverage

Salivary gland

Salivary glands produce fluid containing lubricating proteins, digestive enzymes and antimicrobial molecules. The relative proportions of serous and mucous secretory cells differ between glands and across species, while rodent salivary glands also show pronounced sex-dependent and hormone-regulated specialization of their ductal compartments. As the exact glandular composition may vary between samples, differences in tissue sampling and sex should be considered when interpreting gene expression patterns, both within and between species.

Species coverage

Esophagus

The esophagus transports food from the pharynx to the stomach through coordinated muscular contractions. Its epithelial keratinization and muscular composition vary between species: rodents have a strongly keratinized esophageal epithelium, while humans have a predominantly non-keratinized stratified squamous epithelium, and pigs show more variable keratinization. Histological observations have also revealed a notable difference between pigs and humans, with the porcine esophagus containing more abundant submucosal glands surrounding the esophageal lumen. These anatomical differences may contribute to variation in tissue-level gene expression profiles between species.