TY - JOUR A1 - Liu, Ruiqi A1 - Friedrich, Mike A1 - Hemmen, Katherina A1 - Jansen, Kerstin A1 - Adolfi, Mateus C. A1 - Schartl, Manfred A1 - Heinze, Katrin G. T1 - Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism JF - Frontiers in Endocrinology N2 - Xiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by Förster Resonance Energy Transfer (FRET) that wild-type Xiphophorus Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- vs. homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish. KW - fluorescence lifetime imaging microscopy KW - Förster Resonance Energy Transfer KW - Mc4r KW - puberty KW - Xiphophorus Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-354261 SN - 1664-2392 VL - 14 ER - TY - JOUR A1 - Sendell-Price, Ashley T. A1 - Tulenko, Frank J. A1 - Pettersson, Mats A1 - Kang, Du A1 - Montandon, Margo A1 - Winkler, Sylke A1 - Kulb, Kathleen A1 - Naylor, Gavin P. A1 - Phillippy, Adam A1 - Fedrigo, Olivier A1 - Mountcastle, Jacquelyn A1 - Balacco, Jennifer R. A1 - Dutra, Amalia A1 - Dale, Rebecca E. A1 - Haase, Bettina A1 - Jarvis, Erich D. A1 - Myers, Gene A1 - Burgess, Shawn M. A1 - Currie, Peter D. A1 - Andersson, Leif A1 - Schartl, Manfred T1 - Low mutation rate in epaulette sharks is consistent with a slow rate of evolution in sharks JF - Nature Communications N2 - Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10\(^{−10}\) per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate. KW - evolutionary genetics KW - genomics KW - molecular evolution Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357827 VL - 14 ER -