The table shows the list of considered species named in both the scientific and common name (on the left) and their link in the NCBI browser (on the right).

(DOCX)</p

The table reports the CUB and CU values for each amino acid in all the NDC muscle genes considered.

Every gene is divided in a specific page (on the bottom) across species (on the top). (XLSX)</p

CU values in <i>Homo sapiens</i> muscle, skin, and kidney genes.

Heat plots were generated using R package gplots. Rows were clustered based on Euclidean distance. The color coding varies from dark blue to red with low to high CU values, respectively. Hierarchical clustering of synonymous codon usage in all studied genes in different tissues (muscle, skin and kidney) in HSA was generated. The heat plot graphs show that the clustering of frequently used codons (in red) and rarely used codons (dark blue) greatly varies among genes and tissues. In muscle genes, extremely biased codons (low CU values, key color dark blue, or high CU values, key color dark red) are tightly clustered in terms of both gene and codon types, while intermediate CU values (key color light blue to yellow) are more dispersed in the trees (panel A). Among muscle genes, only DMD does not show any extreme CUB, since no red spots (corresponding to higher CU values) occur (Fig 1A). The CUB fingerprint of skin genes (panel B) shows a prevalent low CU values codons (dark blue), with a few dispersed, not clustered, inhomogeneous distributed yellow-red spots (intermediate and high CU values). CU clusters are less defined compared to muscle. In kidney genes (panel C), the CUB fingerprint also differs from the other two gene groups. The vast majority of genes have low or intermediate CU values (wide and diffuse yellow-blue spot clusters) with a cluster of high CU values closely clustered and related to UMOD, BSND, SLC22A8, MIOX, AQP6, PKD1, SLC12A3, and GGACT genes. Interestingly all of these genes are DC.</p

The table lists all the codon usage p-value, calculated all the considered genes across species, in the three tissues (muscle, skin and kidney).

(XLSX)</p

The table lists all the codon usage p-value, calculated in all the considered <i>Homo sapiens</i> genes, both DC and NDC genes in the three tissues (muscle, skin and kidney).

(TXT)</p

The table reports the CUB and CU values for each amino acid in all the NDC skin genes considered.

Every gene is divided in a specific page (on the bottom) across species (on the top). (XLS)</p

The table shows the list of <i>Homo sapiens</i> genes, prioritized in skin tissue, using the Human Protein Atlas database (https://www.proteinatlas.org/).

In order to prioritize skin genes, we selected those with higher expressions from the skin-enriched genes list of the Human Protein Atlas database (https://www.proteinatlas.org/search/tissue_specificity_rna:skin;Tissue enriched+AND+sort_by:tissue+specific+score+AND+show_columns:groupenriched). All data (RNA, TS, TPM, Protein expression scores and Tissue specificity) were also obtained by the Human Protein Atlas database. *RNA TS TPM indicates RNA level reported as mean TPM (transcripts per million), in referred tissue, skin in this case. **Protein expression scores are based on a best estimate of the "true" protein expression from a knowledge-based annotation in the selected tissue, skin in this case. ***Tissue specificity is based on data found in the graph called “HPA tissue dataset”, a sub-category of the “RNA sample summary” section in the HPA site, for each gene. The RNA summary section shows normal distribution of individual samples across the datasets of multiple RNA-seq analyses visualized with box plots. “Only” is used for a gene transcript present only in the specific tissue (skin). “Predominantly” is used when the majority of a gene transcript is present in the specific tissue (skin). “All” is used for a gene transcript present in all tissues. (DOCX)</p

Number of extremely biased codons (“zero-codons”) found in DC and NDC tissue-specific genes across mammals.

Panel A and B show on graphs the same data reported in Table 1, to better appreciate the CUB trend and the number of “zero codons”. Specifically, the number of extremely biased codons (“zero-codons”) in NDC and DC gene tissues are shown in panel A and panel B, respectively. On the X-axis are listed the mammals’ species in an evolutionary order; in the Y-axis the cardinal number of “zero codons”. Blue, red, and green bars represent kidney, muscle, and skin tissues genes, respectively.</p

CU values across mammals.

Heat plots were generated using R package gplots. Rows were clustered based on Euclidean distance. The color key of CU values varies from blue to red with low to high values of the CUB respectively. CU values in all 60 tissue-specific genes across 15 mammalian species in the metazoan phylogenetic tree are shown in panels A, B, and C, and CU values of single genes in all species are shown in panels D, E, and F. Tissue-specific CUB fingerprints are very evident with a conserved trend across mammals (panels A, B, C). Codons CAG, AAG, CAC, GAC, GAG, AUC, AAC, UAC, UGC, and UUC are the most frequently used codons (red spots) in all tissues and across mammals, while codons UUA, CUA, UCG, CGU, CUU, GUA, CGA, AUA, UCA, UUG, and GCG are the rarest codons (blue spots) in muscle and skin but not in kidney genes. Muscle (panel A) and skin (panel B) CUBs do have a similar fingerprint, although muscle gens have much more codons with lower CU values compared to skin genes; kidney genes show a very different clustering. Panels D, E, and F show gene CU values grouping all mammals. Although clear clustering is poorly visible, tissues have different CUB fingerprints characterized by different gene-related dendrograms. Indeed, 13/30 genes in muscle (panel D), 4/40 genes in skin (panel E) and 8/20 genes in kidney (panel F) show high CU values clusters. Codon types also vary accordingly to CU values since high CU values are clustered in the above listed gene groups. This finding supports that CU values have a tissue-related fingerprint which is still maintained grouping all mammals, and that some gene-specific CU values and codon types are observable.</p

The table reports the CUB and CU values for each amino acid in all the DC kidney genes considered.

Every gene is divided in a specific page (on the bottom) across species (on the top). (XLS)</p