23 research outputs found
Molecular evolution of the hyaluronan synthase 2 gene in mammals: implications for adaptations to the subterranean niche and cancer resistance
The naked mole-rat (NMR) Heterocephalus glaber is a unique and fascinating mammal exhibiting many unusual adaptations to a subterranean lifestyle. The recent discovery of their resistance to cancer and exceptional longevity has opened up new and important avenues of research. Part of this resistance to cancer has been attributed to the fact that NMRs produce a modified form of hyaluronan—a key constituent of the extracellular matrix—that is thought to confer increased elasticity of the skin as an adaptation for living in narrow tunnels. This so-called high molecular mass hyaluronan (HMM-HA) stems from two apparently unique substitutions in the hyaluronan synthase 2 enzyme (HAS2). To test whether other subterranean mammals with similar selection pressures also show molecular adaptation in their HAS2 gene, we sequenced the HAS2 gene for 11 subterranean mammals and closely related species, and combined these with data from 57 other mammals. Comparative screening revealed that one of the two putatively important HAS2 substitutions in the NMR predicted to have a significant effect on hyaluronan synthase function was uniquely shared by all African mole-rats. Interestingly, we also identified multiple other amino acid substitutions in key domains of the HAS2 molecule, although the biological consequences of these for hyaluronan synthesis remain to be determined. Despite these results, we found evidence of strong purifying selection acting on the HAS2 gene across all mammals, and the NMR remains unique in its particular HAS2 sequence. Our results indicate that more work is needed to determine whether the apparent cancer resistance seen in NMR is shared by other members of the African mole-rat clade.National Research Foundation (South Africa
Molecular evolution of the hyaluronan synthase 2 gene in mammals : implications for adaptations to the subterranean niche and cancer resistance
The naked mole-rat (NMR) Heterocephalus glaber is a unique and fascinating mammal
exhibiting many unusual adaptations to a subterranean lifestyle. The recent discovery of
their resistance to cancer and exceptional longevity has opened up new and important
avenues of research. Part of this resistance to cancer has been attributed to the fact that
NMRs produce a modified form of hyaluronan—a key constituent of the extracellular
matrix—that is thought to confer increased elasticity of the skin as an adaptation for
living in narrow tunnels. This so-called high molecular mass hyaluronan (HMM-HA)
stems from two apparently unique substitutions in the hyaluronan synthase 2 enzyme
(HAS2). To test whether other subterranean mammals with similar selection pressures
also show molecular adaptation in their HAS2 gene, we sequenced the HAS2 gene for 11
subterranean mammals and closely related species, and combined these with data from 57 other mammals. Comparative screening revealed that one of the two putatively important
HAS2 substitutions in the NMR predicted to have a significant effect on hyaluronan
synthase function was uniquely shared by all African mole-rats. Interestingly, we also
identified multiple other amino acid substitutions in key domains of the HAS2 molecule,
although the biological consequences of these for hyaluronan synthesis remain to be
determined. Despite these results, we found evidence of strong purifying selection acting
on the HAS2 gene across all mammals, and the NMR remains unique in its particular
HAS2 sequence. Our results indicate that more work is needed to determine whether the
apparent cancer resistance seen in NMR is shared by other members of the African molerat
clade.DST-NRF SARChI Chair for Behavioural Ecology and Physiology.European Research
Council.http://rsbl.royalsocietypublishing2016-05-31hb201
Family wide molecular adaptations to underground life in African mole-rats revealed by phylogenomic analysis
During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the
most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food,
and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche,
African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant
storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has
probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic
specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the
transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing
genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six
genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the
mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis,
aging, morphological development, and sociality. By combining these results with gene ontology annotation and
protein–protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular
evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the
extreme phenotypic traits exhibited by this group.The European Research Council (ERC Starting grant 310482 [EVOGENO]) awarded to S.J.R.; the DST-NRF SARChI Chair of Mammalian Behavioral
Ecology and Physiology (grant number 64756) (funds to N.C.B.).http://mbe.oxfordjournals.orghb201
Molecular evolution of growth hormone and insulin-like growth factor 1 receptors in long-lived, small-bodied mammals
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.DST–NRF SARChI Chair for Behavioural Ecology and Physiology (64756), the European Research Council (310482 EVOGENO) and the National Science Foundation (DEB-0949759).http//www.elsevier.com/locate/genehb201
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Thresholds for adding degraded tropical forest to the conservation estate
Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked
Limited evidence for parallel molecular adaptations associated with the subterranean niche in mammals : a comparative study of three superorders
Among mammals, several lineages have independently adapted to a subterranean niche and possess similar phenotypic
traits for burrowing (e.g., cylindrical bodies, short limbs, and absent pinnae). Previous research on mole-rats has revealed
molecular adaptations for coping with reduced oxygen, elevated carbon dioxide, and the absence of light. In contrast,
almost nothing is known regarding molecular adaptations in other subterranean lineages (e.g., true moles and golden
moles). Therefore, the extent to which the recurrent phenotypic adaptations of divergent subterranean taxa have arisen
via parallel routes of molecular evolution remains untested. To address these issues, we analyzed 8,000 loci in 15
representative subterranean taxa of four independent transitions to an underground niche for signatures of positive
selection and convergent amino acid substitutions. Complementary analyses were performed in nonsubterranean
“control” taxa to assess the biological significance of results. We found comparable numbers of positively selected genes
in each of the four subterranean groups; however, correspondence in terms of gene identity between gene sets was low.
Furthermore, we did not detect evidence of more convergent amino acids among subterranean species pairs compared
with levels found between nonsubterranean controls. Comparisons with nonsubterranean taxa also revealed loci either
under positive selection or with convergent substitutions, with similar functional enrichment (e.g., cell adhesion, immune
response, and coagulation). Given the limited indication that positive selection and convergence occurred in the same
loci, we conclude that selectionmay have acted on different loci across subterraneanmammal lineages to produce similar
phenotypes.The European Research Council (ERC
Starting Grant 310482 [EVOGENO]) awarded to S.J.R. with
additional support from the DST-NRF SARChI Chair for
Behavioural Ecology and Physiology (Grant No. 64756)
awarded to N.C.B. This research utilized Queen Mary’s
Apocrita HPC Facility, supported by QMUL Research-IT
(http://doi.org/10.5281/zenodo.438045).http://mbe.oxfordjournals.orgam2019Mammal Research InstituteZoology and Entomolog