title: Molecular evolution of growth hormone and insulin-like growth factor 1 receptors in long-lived, small-bodied mammals.
abstract: Mammals typically display a robust positive relationship between lifespan and body size. Two groups that deviate markedly from this pattern are bats and African mole-rats, with members of both groups being extremely long-lived given their body size, with the maximum documented lifespan for many species exceeding 20 years. A recent genomics study of the exceptionally long-lived Brandt's bat, Myotis brandtii (41 years), suggested that its longevity and small body size may be at least partly attributed to key amino acid substitutions in the transmembrane domains of the receptors of growth hormone (GH) and insulin-like growth factor 1 (IGF1). However, whereas elevated longevity is likely to be common across all 19 bat families, the reported amino acid substitutions were only observed in two closely related bat families. To test the hypothesis that an altered GH/IGF1 axis relates to the longevity of African mole-rats and bats, we compared and analysed the homologous coding gene sequences in genomic and transcriptomic data from 26 bat species, five mole-rats and 38 outgroup species. Phylogenetic analyses of both genes recovered the majority of nodes in the currently accepted species tree with high support. Compared to other clades, such as primates and carnivores, the bats and rodents had longer branch lengths. The single 24 amino acid transmembrane domain of IGF1R was found to be more conserved across mammals compared to that of GHR. Within bats, considerable variation in the transmembrane domain of GHR was found, including a previously unreported deletion in Emballonuridae. The transmembrane domains of rodents were found to be more conserved, with mole-rats lacking uniquely conserved amino acid substitutions. Molecular evolutionary analyses showed that both genes were under purifying selection in bats and mole-rats. Our findings suggest that while the previously documented mutations may confer some additional lifespan to Myotis bats, other, as yet unknown, genetic differences are likely to account for the long lifespans observed in many bat and mole-rat species.
authors: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. Electronic address: kalinadavies@gmail.com.
authors: Kalina T J
authors: KT
authors: Davies
authors: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. Electronic address: g.tsagkogeorga@qmul.ac.uk.
authors: Georgia
authors: G
authors: Tsagkogeorga
authors: Mammal Research Institute, Department of Zoology & Entomology, University of Pretoria, Private Bag X20, 0028 South Africa. Electronic address: ncbennett@zoology.up.ac.za.
authors: Nigel C
authors: NC
authors: Bennett
authors: Department of Ecology and Evolution, State University of New York at Stony Brook, 650 Life Sciences Building, Stony Brook, NY 11794-5245, USA. Electronic address: liliana.davalos-alvarez@stonybrook.edu.
authors: Liliana M
authors: LM
authors: Dávalos
authors: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. Electronic address: c.g.faulkes@qmul.ac.uk.
authors: Christopher G
authors: CG
authors: Faulkes
authors: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. Electronic address: s.j.rossiter@qmul.ac.uk.
authors: Stephen J
authors: SJ
authors: Rossiter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D049628:Body Size / Q000235:genetics*; D002685:Chiroptera / Q000235:genetics*; D019143:Evolution, Molecular; D049810:Genetic Speciation; D014644:Genetic Variation; D008136:Longevity / Q000235:genetics*; D019577:Mole Rats / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D011986:Receptors, Somatotropin / Q000235:genetics*
chemical_list: D011986:Receptors, Somatotropin; D017526:Receptor, IGF Type 1
keywords: Bats; Longevity; Mammals; Mole-rats; Transmembrane domains