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Fig. 1 | BMC Genomics

Fig. 1

From: Functional analysis and transcriptional output of the Göttingen minipig genome

Fig. 1

Multi-species sequence comparisons and assessment on drug binding. a Sequence identities between 1:1 orthologous transcripts and proteins of human, Rhesus macaque, Cynomolgus macaque, minipig, rat, and mouse. The 5’ UTR, CDS, and 3’ UTR of ~35,700 orthologous mRNAs (including splice variants) and of ~28,400 orthologous proteins were considered separately for the calculation of pairwise sequence identities in comparison to human. The relative number of 1:1 orthologous sequences was plotted against the sequence identities. Note that the peak sequence identities for the UTRs are significantly lower between humans and non-primates than for the coding regions. b Peroxisome proliferator-activated receptor alpha (PPARα) small molecule binding pocket analysis across multiple species. X-ray crystal structure of the ligand binding domain of human PPARα (magenta) with the dual PPARα/γ agonist aleglitazar (cyan) and with a 13-residue fragment of the SRC1 receptor co-activator motif 3 (green). Sequence alignments of PPARα orthologs from multiple species indicate that the contact residues (*) are fully conserved between human, macaques, and pigs while mouse and rat have sequence differences at three positions (P272, M279, I332) in comparison to the other species (I272, T279, V332). The inset shows the binding cavity in more detail and the non-conserved amino acids highlighted in a stick representation. PDB code: 3G8I. c Vascular endothelial growth factor (VEGF) epitope analysis for four different antibodies across multiple species. Depicted is the surface of human VEGF homodimer (light grey/dark grey) with residues relevant for antibody binding colored in red. Sequence alignments of VEGF orthologs from multiple species indicate for each antibody good conservation of contact residues (*) in human, macaques, and pigs, but not in rodents. Therefore cross-species reactivity is poor for mAb 4.6.1, the parent antibody of Avastin, and Y0317 (Lucentis) which are a product of immune response against hVEGF in mouse, and for the single-chain variable fragment (scFv) L3H6, targeting a different less conserved epitope. G6-Fab, derived from a synthetic antibody phage library, however shows good cross-reactivity due to full conservation of the functional epitope. PDB code: 1FLT

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