Cetacea are natural knockouts for IL20
The Cetacea infraorder comprises a very unique group within the mammalian lineage. While sharing common ancestors with terrestrial mammals, their exclusive dependence on aquatic environments makes them attractive models to explore the landscape of molecular shifts in radical habitat transitions. Among their diverse anatomical and physiological solutions, we find detectable genetic remodeling of the immune system. In agreement, here we show that the gene sequence of interleukin-20 (IL20) displays unambiguous signs of inactivation with several disruptive mutations, including stop codons, insertions, and a conserved trans-species mutation abolishing a canonical splice site, in nine analyzed cetacean genomes. Considering the suggested role of IL20 in skin immunity processes, including inflammation, epithelization, and remodeling, we propose that gene inactivation follows specific adaptations of cetacean skin to the aquatic environment, in frame with the less-is-more hypothesis.
KeywordsCetacea Immune system IL20 Gene loss Skin
This work was supported by Norte2020 and FEDER (Coral - Sustainable Ocean Exploitation - Norte-01-0145-FEDER-000036).
- Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, Klunker S, Meyer N, O’Mahony L, Palomares O, Rhyner C, Quaked N, Schaffartzik A, van de Veen W, Zeller S, Zimmermann M, Akdis CA (2011) Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases J Allergy Clin Immunol 127:701–721.e770 doi: https://doi.org/10.1016/j.jaci.2010.11.050, 721.e70CrossRefGoogle Scholar
- Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S, Eagan M, Foster D, Haldeman BA, Hammond A, Haugen H, Jelinek L, Kelly JD, Madden K, Maurer MF, Parrish-Novak J, Prunkard D, Sexson S, Sprecher C, Waggie K, West J, Whitmore TE, Yao L, Kuechle MK, Dale BA, Chandrasekher YA (2001) Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104:9–19CrossRefGoogle Scholar
- Morris JJ, Lenski RE, Zinser ER (2012) The Black Queen Hypothesis: evolution of dependencies through adaptive gene loss. mBio 3. https://doi.org/10.1128/mBio.00036-12
- Romer J, Hasselager E, Norby PL, Steiniche T, Thorn Clausen J, Kragballe K (2003) Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol. J Invest Dermatol 121:1306–1311. https://doi.org/10.1111/j.1523-1747.2003.12626.x CrossRefPubMedGoogle Scholar
- Sadier A et al (2018) Evidence for multifactorial processes underlying phenotypic variation in bat visual opsins bioRxiv. https://doi.org/10.1101/300301
- Sokolov VEE (1982) Mammalian skin. University of California Press, Berkeley and Los AngelesGoogle Scholar
- Wolk K, Haugen HS, Xu W, Witte E, Waggie K, Anderson M, vom Baur E, Witte K, Warszawska K, Philipp S, Johnson-Leger C, Volk HD, Sterry W, Sabat R (2009) IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med (Berl) 87:523–536. https://doi.org/10.1007/s00109-009-0457-0 CrossRefGoogle Scholar
- Yang Z (1998) Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol 15:568–573. https://doi.org/10.1093/oxfordjournals.molbev.a025957 CrossRefPubMedGoogle Scholar