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Evolutionary proteomeTissue specificity across mammalsConservation of gene expression across species
Evolutionary methods
Evolutionary proteomeThe Human Protein Atlas includes RNA expression data from four additional mammalian species: macaque, pig, mouse and rat. Together with the human reference, these datasets provide an evolutionary perspective on gene expression across the mammalian body, enabling exploration of both conserved expression patterns and species-specific differences. This resource provides a user-friendly overview of gene expression across organs and tissues, with an additional focus on the brain and its anatomically specialized regions. By comparing corresponding genes and tissues across species, it is possible to investigate how gene expression and tissue specialization have been maintained or changed during mammalian evolution. Further details about tissue grouping, specificity classifications, ortholog identification and conservation calculations are provided in the Methods section. Tissue specificity across mammalsGenes differ considerably in their expression patterns across the body. Some are broadly expressed in many tissues, while others show elevated expression in one or a few tissues, reflecting specialized biological functions. Tissue specificity was assessed separately for each species, based on the complete set of available tissues, and genes were classified as tissue enriched, group enriched, tissue enhanced, low tissue specificity or not detected. The heatmap below provides an overview of genes classified as having elevated expression in different tissues across the five mammalian species. It illustrates both similarities and differences in tissue-specific expression patterns, although differences in tissue coverage and sampling should be considered when comparing species.
In addition to these categorical classifications, tissue specificity was quantified using the Tau score, a continuous measure ranging from 0 to 1. A low Tau score indicates broadly distributed expression, whereas a high score indicates expression concentrated in one or a few tissues. The bar plot below compares the distribution of Tau scores across species, providing an overview of the degree of tissue specialization within each transcriptome.
Conservation of gene expression across speciesA central question in comparative biology is whether genes maintain similar expression patterns across species or acquire different tissue-specific functions during evolution. To investigate this, we compared corresponding genes between human and each of the four other mammalian species, using a common set of comparable tissues. Pairwise tissue specificity overlapFor each human gene with a corresponding ortholog in another species, we assessed whether its tissue specificity was preserved. Genes with elevated expression in the same tissues were classified as showing complete, partial or minimal overlap, depending on the proportion of shared elevated tissues. Other categories distinguish genes that remain elevated but in different tissues, genes with elevated expression in only one species, and genes with differences in detection status. These comparisons reveal how individual genes may retain similar tissue-specific functions across species, while others show changes in their expression patterns. The pairwise comparisons can be explored for each species separately, allowing differences relative to human to be investigated in greater detail.
Conservation across all five speciesTo provide a broader evolutionary perspective, the four pairwise comparisons were combined into a single tissue specificity conservation category for each gene. This classification summarizes whether tissue specificity is completely, partially or minimally conserved across the investigated mammals, or whether expression patterns differ between human and the other species. The pie charts below summarize the distribution of these conservation categories across the mammalian body and within the brain. Whole-body tissue specificity conservation
This overview illustrates the extent to which tissue-specific gene expression patterns are conserved across mammals, based on a common set of comparable tissues. Genes are grouped according to their overall conservation category, providing an overview of conserved and divergent expression patterns across the body. Brain regional specificity conservation
The brain contains highly specialized anatomical regions with distinct molecular functions. A corresponding analysis was therefore performed using regional brain RNA expression profiles, allowing conservation of gene expression to be investigated at a finer anatomical level. The resulting overview illustrates how regional expression patterns are maintained or differ across mammalian brains, while accounting for differences in available brain regions and sampling resolution.
Complete conservation (Tissue elevated)
Complete conservation (Low tissue specificity)
Complete conservation (Not detected)
Partial conservation (Tissue elevated)
Partial conservation (Low tissue specificity)
Partial conservation (Not detected)
Limited conservation (Tissue elevated)
Limited conservation (Low tissue specificity)
Limited conservation (Not detected)
Tissue elevation shift
Human-specific tissue elevated
Non-human tissue elevated
Human-specific detected
Human not detected
Unassessed
Complete conservation (Region elevated)
Complete conservation (Low region specificity)
Complete conservation (Not detected)
Partial conservation (Region elevated)
Partial conservation (Low region specificity)
Partial conservation (Not detected)
Limited conservation (Region elevated)
Limited conservation (Low region specificity)
Limited conservation (Not detected)
Region elevation shift
Human-specific region elevated
Non-human region elevated
Human-specific detected
Human not detected
Unassessed
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The Human Protein Atlas project is funded
