Genomic evidence for the parallel regression of melatonin synthesis and signaling pathways in placental mammals

Christopher A Emerling; Mark S Springer; John Gatesy; Zachary Jones; Deana Hamilton; David Xia-Zhu; Matt Collin; Frédéric Delsuc

doi:10.12688/openreseurope.13795.2

Genomic evidence for the parallel regression of melatonin synthesis and signaling pathways in placental mammals

Open Res Eur. 2021 Dec 13:1:75. doi: 10.12688/openreseurope.13795.2. eCollection 2021.

Authors

Christopher A Emerling^{1

2

3}, Mark S Springer⁴, John Gatesy⁵, Zachary Jones¹, Deana Hamilton¹, David Xia-Zhu¹, Matt Collin⁴, Frédéric Delsuc²

Affiliations

¹ Museum of Vertebrate Zoology, University of California, Berkeley, Berkeley, CA, 94720, USA.
² Institut des Sciences de l'Evolution de Montpellier (ISEM), CNRS, IRD, EPHE, Université de Montpellier, Montpellier, France.
³ Biology Department, Reedley College, Reedley, CA, 93654, USA.
⁴ Department of Evolution, Ecology, and Organismal Biology, University of California, Riverside, Riverside, CA, 92521, USA.
⁵ Division of Vertebrate Zoology, American Museum of Natural History, New York, NY, 10024, USA.

Abstract

Background: The study of regressive evolution has yielded a wealth of examples where the underlying genes bear molecular signatures of trait degradation, such as pseudogenization or deletion. Typically, it appears that such disrupted genes are limited to the function of the regressed trait, whereas pleiotropic genes tend to be maintained by natural selection to support their myriad purposes. One such set of pleiotropic genes is involved in the synthesis ( AANAT, ASMT) and signaling ( MTNR1A, MTNR1B) of melatonin, a hormone secreted by the vertebrate pineal gland. Melatonin provides a signal of environmental darkness, thereby influencing the circadian and circannual rhythmicity of numerous physiological traits. Therefore, the complete loss of a pineal gland and the underlying melatonin pathway genes seems likely to be maladaptive, unless compensated by extrapineal sources of melatonin. Methods: We examined AANAT, ASMT, MTNR1A and MTNR1B in 123 vertebrate species, including pineal-less placental mammals and crocodylians. We searched for inactivating mutations and modelled selective pressures (dN/dS) to test whether the genes remain functionally intact. Results: We report that crocodylians retain intact melatonin genes and express AANAT and ASMT in their eyes, whereas all four genes have been repeatedly inactivated in the pineal-less xenarthrans, pangolins, sirenians, and whales. Furthermore, colugos have lost these genes, and several lineages of subterranean mammals have partial melatonin pathway dysfunction. These results are supported by the presence of shared inactivating mutations across clades and analyses of selection pressure based on the ratio of non-synonymous to synonymous substitutions (dN/dS), suggesting extended periods of relaxed selection on these genes. Conclusions: The losses of melatonin synthesis and signaling date to tens of millions of years ago in several lineages of placental mammals, raising questions about the evolutionary resilience of pleiotropic genes, and the causes and consequences of losing melatonin pathways in these species.

Keywords: Dermoptera; Melatonin; Pholidota; Pseudogene; Sirenia; Xenarthra.

Grants and funding

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the European Research Council (ERC) grant agreement No [683257]. This research was also supported by a National Science Foundation (NSF) Postdoctoral Research Fellowship in Biology (award no. 1523943; C.A.E.), an NSF Postdoctoral Fellow Research Opportunities in Europe award (C.A.E.), the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. PCOFUND-GA-2013-609102, through the PRESTIGE programme coordinated by Campus France (C.A.E.) and an NSF DEB- 1457735 grant to J.G and M.S.S.