Fig. 4

Emergence and development of major structural features in the N- and C-terminal regions of SLRPs. The major results of the study are illustrated. The upper panel illustrates the presence (cyan-bar) or absence (no bar) of elements in the variable N- and C-terminal regions of class II and III SLRPs, while the lower panel depicts the interrelationships of jawed vertebrates. Closed bars (cyan) represent that specific changes of the terminal region of a SLRP occurred between the splits of two lineages (see lower panel), thus pinpointing the evolutionary point of its development. Open faint bars represent the presence of a sulfotyrosine-rich or basic N-terminal region in all sequences in the dataset of that SLRP; hence, its development arose earlier in vertebrate evolution. No major changes occurred in the N-terminal region of lumican, PRELP, epiphycan or opticin during the evolution of jawed vertebrates (opticin-dataset does not contain sequences from cartilaginous fish). The sulfotyrosine-rich N-terminal extension of osteoadherin is the evolutionarily first observable change in the terminal regions of the SLRPs. The extension must have developed in a progenitor to all extant bony vertebrates since a sulfotyrosine-rich N-terminal region is not present in osteoadherin from cartilaginous fish but is present in all other sequences of the dataset. In the split between ray-finned and lobe-finned fish, an extension of the N-terminal region of keratocan developed in sarcopterygians (although it is not present in amphibians). Additionally, a sulfotyrosine-rich N-terminal region is generally present in mimecan of the sarcopterygian species. In the C-terminal region of osteoadherin, an extension developed containing a cluster of acidic residues after the split between lobe-finned fish and tetrapods. The evolutionarily newest structural feature in the terminal region of class II and III SLRPs happened in fibromodulin with the emergence of a sulfotyrosine-rich N-terminal extension in a progenitor to all extant amniotes. sTyr = sulfotyrosine; NTE = N-terminal extension; NTR = N-terminal region; CTE = C-terminal extension