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 the 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 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 within the 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.

Molecular Evolution of the TET Gene Family in Mammals

“…Figure 4 shows the plots of the summed PP values of total convergent substitutions (that is, both the convergent and parallel substitutions) vs. the summed PP values of total divergent substitutions across all of the branch-pair comparisons for the TET1, TET2 and TET3 phylogenetic trees. Similar to other studies [ 28 , 29 ], there was a linear relationship between the number of divergent and convergent substitutions, and the divergent substitutions were more abundant than convergent substitutions. In the case of TET3, although these relationships were noticeable, we also observed extremely lower divergence probabilities and somewhat higher convergence probabilities compared to TET1 and TET2.…”

Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis

“…These included several genes relating to the stability of chromosomes and telomerase activity, as well as genes encoding proteins related to growth, notably GHRHR and GHSR ( growth hormone secretagogue receptor ). Such findings warrant further investigation, but are intriguing given the documented role growth hormone plays in longevity and body size, especially given that the GHR gene is highly conserved across mole-rats ( Davies et al 2014 ). Mole-rats, and the naked mole-rat in particular, have also previously been studied in relation to levels of amyloid beta (Aβ) peptides ( Edrey et al 2013 ), the accumulation of which are thought to be associated with Alzheimer's disease.…”

“…The morphological, physiological and life-history traits displayed by mole-rats make them a valuable group for comparative evolutionary studies. Yet, while the genomes of two naked mole-rat individuals and one Damaraland mole-rat ( F. damarensis ) have recently been sequenced ( Kim et al 2011 ; Fang, Seim, et al 2014 ; Keane et al 2014 ), very little is known regarding molecular adaptations across the family, with only a small number of candidate gene studies (e.g., [ Edrey et al 2012 ; Davies et al 2014 ; Stathopoulos et al 2014 ; Faulkes et al 2015 ]). Here, to identify genes that may have been targets of selection across African mole-rats, we undertook transcriptome sequencing of seven phylogenetically divergent species.…”

Investigation of the EIL/EIN3 Transcription Factor Gene Family Members and Their Expression Levels in the Early Stage of Cotton Fiber Development

“…The variation in gene arrangement is the key factor involved in the evolution of multigene families [43][44][45]. To elucidate the organizational diversities of cotton EIL/EIN3 genes, the exon/intron arrangements of these cotton genes were investigated.…”