Comparative genomics of monotremes provides insights into the early evolution of mammalian epidermal differentiation genes

Abstract

The function of the skin as a barrier against the environment depends on the differentiation of epidermal keratinocytes into highly resilient corneocytes that form the outermost skin layer. Many genes encoding structural components of corneocytes are clustered in the epidermal differentiation complex (EDC), which has been described in placental and marsupial mammals as well as non-mammalian tetrapods. Here, we analyzed the genomes of the platypus (Ornithorhynchus anatinus) and the echidna (Tachyglossus aculeatus) to determine the gene composition of the EDC in the basal clade of mammals, the monotremes. We report that mammal-specific subfamilies of EDC genes encoding small proline-rich proteins (SPRRs) and late cornified envelope proteins as well as single-copy EDC genes such as involucrin are conserved in monotremes, suggesting that they have originated in stem mammals. Monotremes have at least one gene homologous to the group of filaggrin (FLG), FLG2 and hornerin (HRNR) in placental mammals, but no clear one-to-one pairwise ortholog of either FLG, FLG2 or HRNR. Caspase-14, a keratinocyte differentiation-associated protease implicated in the processing of filaggrin, is encoded by at least 3 gene copies in the echidna. Our results reveal evolutionarily conserved and clade-specific features of the genetic regulation of epidermal differentiation in monotremes.

Comparative genomics of sirenians reveals evolution of filaggrin and caspase-14 upon adaptation of the epidermis to aquatic life

“…However, FLG and CASP14 have not been strictly interdependent during the evolution of mammals. CASP14 is present in monotremes (platypus and echidna), whereas an SFTP with amino acid sequence features characteristic for FLG is missing 12 . CASP14 has been lost in cetaceans, whereas FLG has been conserved, as mention above, in a subgroup of cetaceans 41 .…”

“…A cluster of genes encoding protein components of the cornified envelope of epidermal keratinocytes is known as the epidermal differentiation complex (EDC). The EDC is located on human chromosome 1q21.3, and homologous gene clusters have been identified in other mammalian species 9 – 12 as well as non-mammalian tetrapods 13 – 18 . The EDC is bordered by genes of the S100A family, which are considered the evolutionarily ancestors of other EDC gene types 13 , 19 .…”