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 substitutionswere 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 themajority 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 IGF1Rwas found to bemore 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
andmole-rats. Our findings suggest thatwhile the previously documentedmutations 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.