Abstract:Background: The Weddell Seal (Leptonychotes weddelli) represents a remarkable example of adaptation to diving among marine mammals. This species is capable of diving > 900 m deep and remaining underwater for more than 60 min. A number of key physiological specializations have been identified, including the low levels of aerobic, lipid-based metabolism under hypoxia, significant increase in oxygen storage in blood and muscle; high blood volume and extreme cardiovascular control. These adaptations have been link… Show more
“…Using Basic Local Alignment Search Tool, we identified these seal proteins and mapped them to gene families containing 60S ribosomal proteins, cytokines, calcium-binding proteins, histones, and ubiquitin proteasome (Supplementary Table 3 ). The high rate of protein-coding gene family expansions in the Weddell seal is consistent with a previous analysis of microRNA family size showing high rates of gain and loss in the Weddell seal lineage versus dog 38 . Fig.…”
The Weddell seal (Leptonychotes weddellii) thrives in its extreme Antarctic environment. We generated the Weddell seal genome assembly and a high-quality annotation to investigate genome-wide evolutionary pressures that underlie its phenotype and to study genes implicated in hypoxia tolerance and a lipid-based metabolism. Genome-wide analyses included gene family expansion/contraction, positive selection, and diverged sequence (acceleration) compared to other placental mammals, identifying selection in coding and non-coding sequence in five pathways that may shape cardiovascular phenotype. Lipid metabolism as well as hypoxia genes contained more accelerated regions in the Weddell seal compared to genomic background. Top-significant genes were SUMO2 and EP300; both regulate hypoxia inducible factor signaling. Liver expression of four genes with the strongest acceleration signals differ between Weddell seals and a terrestrial mammal, sheep. We also report a high-density lipoprotein-like particle in Weddell seal serum not present in other mammals, including the shallow-diving harbor seal.
“…Using Basic Local Alignment Search Tool, we identified these seal proteins and mapped them to gene families containing 60S ribosomal proteins, cytokines, calcium-binding proteins, histones, and ubiquitin proteasome (Supplementary Table 3 ). The high rate of protein-coding gene family expansions in the Weddell seal is consistent with a previous analysis of microRNA family size showing high rates of gain and loss in the Weddell seal lineage versus dog 38 . Fig.…”
The Weddell seal (Leptonychotes weddellii) thrives in its extreme Antarctic environment. We generated the Weddell seal genome assembly and a high-quality annotation to investigate genome-wide evolutionary pressures that underlie its phenotype and to study genes implicated in hypoxia tolerance and a lipid-based metabolism. Genome-wide analyses included gene family expansion/contraction, positive selection, and diverged sequence (acceleration) compared to other placental mammals, identifying selection in coding and non-coding sequence in five pathways that may shape cardiovascular phenotype. Lipid metabolism as well as hypoxia genes contained more accelerated regions in the Weddell seal compared to genomic background. Top-significant genes were SUMO2 and EP300; both regulate hypoxia inducible factor signaling. Liver expression of four genes with the strongest acceleration signals differ between Weddell seals and a terrestrial mammal, sheep. We also report a high-density lipoprotein-like particle in Weddell seal serum not present in other mammals, including the shallow-diving harbor seal.
“…In Steller sea lions ( Eumetopias jubatus ), mass-specific total body oxygen stores not only increase with age, but shift predominantly to muscle for primary oxygen storage ( Richmond et al, 2006 ). Similar age-related changes in oxygen-storing capacity have been observed in other pinniped species, such as the Weddell seal ( Leptonychotes weddellii ) ( Penso-Dolfin et al, 2020 ). Expression and activity of antioxidant enzymes were also found to increase with maturation in hooded seals ( Cystophora cristata ) and ringed seals ( Pusa hispida ) ( Elsner et al, 1998 ; Vázquez-Medina et al, 2006 , 2011b ).…”
Marine mammals such as northern elephant seals (NES) routinely experience hypoxemia and ischemia-reperfusion events to many tissues during deep dives with no apparent adverse effects. Adaptations to diving include increased antioxidants and elevated oxygen storage capacity associated with high hemoprotein content in blood and muscle. The natural turnover of heme by heme oxygenase enzymes (encoded by HMOX1 and HMOX2) produces endogenous carbon monoxide (CO), which is present at high levels in NES blood and has been shown to have cytoprotective effects in laboratory systems exposed to hypoxia. To understand how pathways associated with endogenous CO production and signaling change across ontogeny in diving mammals, we measured muscle CO and baseline expression of 17 CO-related genes in skeletal muscle and whole blood of three age classes of NES. Muscle CO levels approached those of animals exposed to high exogenous CO, increased with age, and were significantly correlated with gene expression levels. Muscle expression of genes associated with CO production and antioxidant defenses (HMOX1, BVR, GPX3, PRDX1) increased with age and was highest in adult females, while that of genes associated with protection from lipid peroxidation (GPX4, PRDX6, PRDX1, SIRT1) was highest in adult males. In contrast, muscle expression of mitochondrial biogenesis regulators (PGC1A, ESRRA, ESRRG) was highest in pups, while genes associated with inflammation (HMOX2, NRF2, IL1B) did not vary with age or sex. Blood expression of genes involved in regulation of inflammation (IL1B, NRF2, BVR, IL10) was highest in pups, while HMOX1, HMOX2 and pro-inflammatory markers (TLR4, CCL4, PRDX1, TNFA) did not vary with age. We propose that ontogenetic upregulation of baseline HMOX1 expression in skeletal muscle of NES may, in part, underlie increases in CO levels and expression of genes encoding antioxidant enzymes. HMOX2, in turn, may play a role in regulating inflammation related to ischemia and reperfusion in muscle and circulating immune cells. Our data suggest putative ontogenetic mechanisms that may enable phocid pups to transition to a deep-diving lifestyle, including high baseline expression of genes associated with mitochondrial biogenesis and immune system activation during postnatal development and increased expression of genes associated with protection from lipid peroxidation in adulthood.
“…Another research demonstrated that during hypoxic events, the upregulation of miR-24, which inhibits apoptosis, combined with the downregulation of miR-210, an indirect stabilizer of HIF1, could potentially promote neuronal preservation and trigger an adaptive hypoxic response in naked mole rats ( Logan et al 2020 ). In the case of aquatic mammals, Penso-Dolfin et al (2020 ) investigated the role of miRNAs in the adaptive evolution of diving capacities in Weddell seals ( Leptonychotes weddelli ). Through differential expression analysis, they identified potential protective mechanisms in individual tissues, particularly relevant to hypoxia tolerance and anti-apoptotic pathways.…”
Aquatic mammals (marine and freshwater species) share significant and similar adaptations, enabling them to tolerate hypoxia during regular breath-hold diving. Despite the established importance of
HIF1A
, a master regulator in the molecular mechanism of hypoxia response, and other associated genes, their role in the evolutionary adaptation of aquatic mammals is not fully understood. In this study, we investigated this topic by employing a candidate gene approach to analyze 11 critical genes involved in the
HIF1A
signaling pathway in aquatic mammals. Our gene analyses included evaluating positive and negative selection, relaxation or constriction of selection, and molecular convergence compared to other terrestrial mammals, including subterranean mammals. Evidence of selection suggested a significant role of negative selection, as well as relaxation of the selective regime in cetaceans for most of these genes. We found that the glutamine 68 variant in the HIF3α protein is unique to cetaceans and initial evaluations indicated a destabilizing effect on protein structure. However, further analyses are necessary to evaluate its functional impact and adaptive relevance in this taxon.
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