Identification and comparative analysis of the epidermal differentiation complex in snakes

Abstract

The epidermis of snakes efficiently protects against dehydration and mechanical stress. However, only few proteins of the epidermal barrier to the environment have so far been identified in snakes. Here, we determined the organization of the Epidermal Differentiation Complex (EDC), a cluster of genes encoding protein constituents of cornified epidermal structures, in snakes and compared it to the EDCs of other squamates and non-squamate reptiles. The EDC of snakes displays shared synteny with that of the green anole lizard, including the presence of a cluster of corneous beta-protein (CBP)/beta-keratin genes. We found that a unique CBP comprising 4 putative beta-sheets and multiple cysteine-rich EDC proteins are conserved in all snakes and other squamates investigated. Comparative genomics of squamates suggests that the evolution of snakes was associated with a gene duplication generating two isoforms of the S100 fused-type protein, scaffoldin, the origin of distinct snake-specific EDC genes, and the loss of other genes that were present in the EDC of the last common ancestor of snakes and lizards. Taken together, our results provide new insights into the evolution of the skin in squamates and a basis for the characterization of the molecular composition of the epidermis in snakes.

Review: Evolution and diversification of corneous beta‐proteins, the characteristic epidermal proteins of reptiles and birds

“…The cladogram is based on Dalla Valle, Nardi, Gelmi, et al () and 2010a that report these main subdivisions. The source for the number of CBPs was for snakes Holthaus et al (); for anolis Dalla Valle, Nardi, Bonazza, et al (2010b); for the Japanese gecko Liu et al (); for birds Greenwold et al (); for crocodilians Holthaus et al () and this review; for turtles Li et al () [Color figure can be viewed at wileyonlinelibrary.com]…”

“…The recent sequencing of various reptile and bird genomes has made it possible not only to identify the CBP gene cluster in all major sauropsid clades, but also to apply comparative genomics (Zheng et al, ) to address the relationship between corneous proteins in sauropsids and mammals (Mlitz et al, ; Strasser et al, ; Figure ). The CBP cluster was found in the EDC on chromosome 25 of the chicken (Alibardi & Toni, ; Greenwold & Sawyer, , ), and in the EDC of all major sauropsid clades (Holthaus et al, , , ; Strasser et al, ). Therefore, proteins formerly termed beta‐keratins have their genes included in the EDC, and are themselves “epidermal differentiation” or “corneous” proteins and not keratins (IF‐proteins).…”

“…In squamates, initial molecular studies indicated that CBP genes were clustered in the lizard Anolis carolinensis and the snake Pantheropis guttata (Dalla Valle, Nardi, Bonazza et al, ; Dalla Valle, Nardi, Toni, Emera, & Alibardi, ). Later studies on the green anole lizard ( A. carolinensis ), the Burmese python ( Python bivittatus ), and king cobra ( Ophiophagus hannah ), showed that most CBP genes are positioned in a single locus that was identified within the EDC (Figure ; Holthaus et al, ; Strasser et al, ). Only one CBP gene is of uncertain location in the green anole and several CBP genes require precise mapping in snakes.…”

“…Even though snakes have lost their limbs and associated appendages like nails and setae, the number of CBP genes is similar to that of the green anole lizard ( A. carolinensis ; Dalla Valle, Nardi, Bonazza et al, ). The Burmese python ( P. bivittaus ) and the King cobra ( O. hannah ) have a genome containing 35 and 36 CBP genes respectively (Holthaus et al, ; Figure ; Supporting Information Figure S1, Pb), while the genome of the green anole lizard contains 40 genes (Dalla Valle, Nardi, Bonazza et al, b; Figure ; Supporting Information Figure S1, Ac). This similar number of CBP copies could derive from the close phylogenetic relation of these species that all belong to the suborder Toxicofera (Pyron, Burbrink, & Wiens, ).…”

“…Normally only one beta‐sheet motif is found in CBPs, but in some squamates, so far in two species of lizards and of snakes, unique proteins with four of these motifs have been identified (Figure c; Supporting Information Figure S3; Holthaus et al, ). The formation of dimers between CBPs with four motifs is supposed to be similar to CBPs with one beta‐sheet motif and to occur through face to face interaction of beta‐sheets (Calvaresi et al, ; Fraser & Parry, ; Holthaus et al, ).…”