Patterns of Genetic Diversity and Gene Flow Associated With an Aridity Gradient in Populations of Common Mole-rats, Cryptomys hottentotus hottentotus

Genetic adaptation is the change of a population toward a phenotype that best fits the present ecological conditions of the environment it inhabits. As environmental conditions change, allele frequencies shift, resulting in different populations of the same species possessing genetic variation and divergent phenotypes. Cooperatively breeding common mole-rats (Cryptomys hottentotus hottentotus) inhabit environments along an aridity gradient in South Africa, which provides an opportunity for local genetic adaptations to occur. Using one mitochondrial gene (cytochrome b) and 3,540 SNP loci across the whole genome, we determined the phylogenetic relationship, population structure and genetic diversity of five populations of C. h. hottentotus located along an aridity gradient. Mitochondrial data identified population-specific clades that were less distinct in the two mesic populations, potentially indicating historical or recent gene flow, or the retention of ancestral haplotypes. Arid and semi-arid populations formed a distinct cluster from the non-arid populations. Genetic diversity and gene flow were higher in arid-dwelling individuals, suggesting greater connectivity and interactions between colonies in arid regions in comparison to mesic ones. Using an Aridity Index, we determined that isolation by environment, rather than isolation by geographical distance, best explains the genetic distance between the populations. Further analyses using target loci may determine if there are differing underlying genetic adaptations among populations of C. h. hottentotus. These analyses could help unravel population differences in response to environmental factors within a subspecies of bathyergid mole-rat and determine the adaptive capacity of this small nonmigratory subterranean rodent species in response to aridification in the face of climate change

Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat.

The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness.This work was supported by a European Research Council grant (grant 294678 Extremeophile Mammal) to G.R.L. E.S.J.S. acknowledges support from the Alexander von Humboldt foundation.This is the final version of the article. It first appeared from Elsevier (Cell Press) via https://doi.org/10.1016/j.celrep.2016.09.03

RNA Sequencing Reveals Differential Expression of Mitochondrial and Oxidation Reduction Genes in the Long-Lived Naked Mole-Rat When Compared to Mice

The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam), a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m), and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics

New insights into morphological adaptation in common mole-rats (Cryptomys hottentotus hottentotus) along an aridity gradient

DATA AVAILABILITY STATEMENT : All data are available as an electronic File S1.Morphological adaptation is the change in the form of an organism that benefits the individual in its current habitat. Mole-rats (family Bathyergidae), despite being subterranean, are impacted by both local and broad-scale environmental conditions that occur above ground. Common mole-rats (Cryptomys hottentotus hottentotus) present an ideal mammalian model system for the study of morphological variation in response to ecology, as this species is found along an aridity gradient and thus can be sampled from geographically non-overlapping populations of the same species along an environmental longitudinal cline. Using the mass of five internal organs, ten skeletal measurements and 3D morphometric analyses of skulls, we assessed the morphology of wild non-breeding individuals from five common mole-rat populations in South Africa. We found that the body mass and mean relative mass of the spleen and kidneys in arid populations was larger, and individuals from arid regions possessed shorter legs and larger inter-shoulder widths compared to individuals from mesic regions. Additionally, arid populations demonstrated greater skull depth, and shape change of features such as angular processes of the lower jaw than mesic individuals, indicating that these distinct geographic populations show differences corresponding to the aridity gradient, potentially in response to environmental factors such as the variation in food sources found between different habitats, in addition to different soil compositions found in the different regions. Arid populations potentially require a stronger jaw and neck musculature associated with mastication to chew xeric-adapted plants and to dig through hard soil types, whereas mesic populations excavate through soft, looser soil and may make use of their front limbs to aid the movement of soils when digging. Aridity influences the morphology of this species and could indicate the impact of environmental changes on speciation and mammalian skull morphology.Natural Environment Research Council.http://www.ecolevol.orghj2024Zoology and EntomologySDG-15:Life on lan

Ageing-associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species.

BACKGROUND: Mammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular readout of lifespan variation among different mammalian species. RESULTS: A large-scale integrated analysis of aDMPs in six different mammals reveals a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This relationship also holds when comparing two different dog breeds with known differences in lifespans. In an ageing cohort of aneuploid mice carrying a complete copy of human chromosome 21, aDMPs accumulate far more rapidly than is seen in human tissues, revealing that DNA methylation at aDMP sites is largely shaped by the nuclear trans-environment and represents a robust molecular readout of the ageing cellular milieu. CONCLUSIONS: Overall, we define the first dynamic molecular readout of lifespan differences among mammalian species and propose that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals

The biology of an isolated Mashona mole-rat population from southern Malawi, with implications for the diversity and biogeography of the genus Fukomys

AVAILABILITY OF DATA AND MATERIALS : GPS of localities, museum voucher numbers, GenBank Accession numbers, and other details about specimens included in analyses are provided in Supplementary Information 2. New DNA sequences were uploaded to GenBank and their accession numbers (OQ559424-OQ559475, OQ442881–OQ442896, OQ442843–OQ442861, OQ559483–OQ559501, OQ559505–OQ559523, OQ442862–OQ442880) are in Supplementary Information 2.The Mashona mole-rat, Fukomys darlingi (Thomas, 1895), is a little studied social African mole-rat (Bathyergidae) from south-astern Africa. Here, we present an integrative study characterizing the genetic diversity of populations assigned to F. darlingi with special focus on animals from Nsanje, southern Malawi. These mole-rats show pronounced differences in body mass and general appearance compared to nominate F. darlingi from Zimbabwe and Mozambique, but their taxonomic status has so far remained unclear. A genetic analysis encompassing all major lineages of the genus Fukomys suggests that this population indeed represents a deeply nested lineage within the F. darlingi clade. The karyotype of the Nsanje mole-rats also corresponds to that of the nominate form, being 2n = 54. While both nuclear and mitochondrial data agree about the assignment of the Nsanje mole-rats to F. darlingi, our analyses revealed substantial mitonuclear discordance for other branches within the Fukomys phylogenetic tree. Nsanje mole-rats are significantly larger than nominate F. darlingi and their ontogeny and reproduction closely resemble similar-sized congeneric species rather than the nominate population. The somatic growth of the Nsanje form is the slowest of all African mole-rats. The maximum life span of F. darlingi is at least 19 years. The observed differences between nominate F. darlingi and mole-rats from Nsanje may be attributed mainly to their different body mass. Our study highlights the advantages of an integrative approach for understanding the diversity of African mole-rats and emphasizes the great intraspecific variability that may be encountered in these underground-dwelling rodents.Open access publishing supported by the National Technical Library in Prague. The grant of the Czech Science Foundation (GAČR) and Grant Agency of University of South Bohemia.https://link.springer.com/journal/13127hj2024Mammal Research InstituteZoology and EntomologyNon

Tissue Oxidative Ecology along an Aridity Gradient in a Mammalian Subterranean Species

Climate change has caused aridification which can alter habitat vegetation, soil and precipitation profiles potentially affecting resident species. Vegetation and soil profiles are important for subterranean mole-rats as increasing aridity causes soils to become harder and geophytes less evenly distributed, and the inter-geophyte distance increases. Mole-rats obtain all water and dietary requirements from geophytes, and thus digging in harder soils may amplify stressors (hyperthermia, dehydration- or exercise-induced damage). This study assessed the oxidative status of the wild common mole-rat along an aridity gradient (arid, semi-arid and mesic). Kidney and liver oxidative markers, including total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Liver oxidative status did not demonstrate any significance with the degree of the aridity gradient. Aridity affected the TAC and OSI of the kidney, with individuals in the most arid habitats possessing the highest TAC. The evolution of increased group size to promote survival in African mole-rats in arid habitats may have resulted in the additional benefit of reduced oxidative stress in the kidneys. The SOD activity of the kidneys was higher than that of the liver with lower oxidative damage, suggesting this species pre-emptively protects its kidneys as these are important for water balance and retention

Phylogenetic Relationships in Pterodroma Petrels Are Obscured by Recent Secondary Contact and Hybridization

The classification of petrels (Pterodroma spp.) from Round Island, near Mauritius in the Indian Ocean, has confounded researchers since their discovery in 1948. In this study we investigate the relationships between Round Island petrels and their closest relatives using evidence from mitochondrial DNA sequence data and ectoparasites. Far from providing clear delimitation of species boundaries, our results reveal that hybridization among species on Round Island has led to genetic leakage between populations from different ocean basins. The most common species on the island, Pterodroma arminjoniana, appears to be hybridizing with two rarer species (P. heraldica and P. neglecta), subverting the reproductive isolation of all three and allowing gene flow. P. heraldica and P. neglecta breed sympatrically in the Pacific Ocean, where P. arminjoniana is absent, but no record of hybridization between these two exists and they remain phenotypically distinct. The breakdown of species boundaries in Round Island petrels followed environmental change (deforestation and changes in species composition due to hunting) within their overlapping ranges. Such multi-species interactions have implications not only for conservation, but also for our understanding of the processes of evolutionary diversification and speciation

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process