Naked mole rats, Heterocephalus glaber - uniquely able to resist cardiac damage.
Part of creationists mythology is the belief that humans stand at the pinnacle of creation, being the supreme creation of their putative designer. Even those who accept the evidence for evolution, like to imagine that somehow evolution was intended to result in humans being at the apex of it.
As you would expect of creationism, those beliefs are counter-factual and so are not supported by the evidence, and, if they are to be believed, paints their putative creator god in a very poor light, not the least because of the very many examples of where, if it had created humans and all the other species, humans come off at best second best, having inferior versions of organs and processes compared to many other species. I list several of these in my popular, illustrated book, The Malevolent Designer: Why Nature's God is not Good, for example, the superior eye of the peregrine falcon, the superior immune system of bats and the fact that elephants and sharks rarely get cancer.
Now we have the example of naked mole rats which are able to suffer anoxia without sustaining damage to their cardiac muscles, so they rarely have heart attacks.
The damage during a heart attack, i.e., when a cardiac artery is blocked by a blood clot, is cell death due to being deprived of oxygen. But Naked mole rats have a unique cardiac metabolism and unique genes, that enable their cardiac muscle cells to survive a period of anoxia.
The reason for this, and the mechanism creationism's creative god could have given humans if it were real and is as omnibenevolent as creationists like to pretend, was discovered by researchers from London, Pretoria and Cambridge, led by Dr. Dunja Aksentijevic of the Centre for Biochemical Pharmacology, William Harvey Research Institute, Bart’s and the London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
The team have just published their findings, open access, in the journal Nature Communications. It is also explained in a Queen Mary University news release:
Secrets of the naked mole-rat: new study reveals how their unique metabolism protects them from heart attacksThe technical detail is in the open access paper in Nature Communications:
This unusual, subterranean mammal with extreme longevity shows genetic adaptations to low oxygen environments which could offer opportunities for advancing other areas of physiological and medical research in humans.
New research, published today in Nature Communications and led by Dr Dunja Aksentijevic in the Faculty of Medicine and Dentistry, has revealed that that the genome of the naked mole-rat contains specific adaptations that allow them to survive in low-oxygen, and even no oxygen environments in their natural habitat. The findings also show the mammals’ distinct cardiometabolic profile helps to avoid damage to their hearts caused by cardiovascular events.
Dr Aksentijevic led the team of scientists from London, Pretoria and Cambridge to sample heart tissue from the naked mole-rat and compared it to samples from other African mole-rat species as well as other evolutionarily divergent mammals.
In this study, they found that the naked mole-rat has a unique expression of genes in heart cells controlling energy generation from sugars resulting in a metabolic profile that is distinct from any of the other mole-rats as well as the other species studied. These unique cardiac metabolic and genetic features of the naked mole-rat heart led to enhanced energy reserves even during blood occlusion and return of blood flow after in vitro simulated heart attack. Collectively, these adaptations result in the naked mole-rat’s tolerance to reduced oxygen and negligible damage to their heart tissue.
Naked mole-rats live in a unique hypoxic and social environment, and we believe these factors have driven the evolution of special adaptations in their hearts that contribute to their exceptional longevity and health span.
Dr Chris G. Faulkes, Lead Author,
Reader (Associate Professor) in Evolutionary Ecology
School of Biological and Behavioural Sciences
Queen Mary University of London, London, UK.Unlike humans, who are prone to heart injury by hypoxia and anoxia caused by blood occlusion during heart attacks, NMR hearts have adapted to evade such damage. Thanks to our research, we are now able to understand the metabolic and genetic mechanisms underpinning this unique level of protection.
Dr Dunja Aksentijevic, lead author
Reader (Associate Professor) in Cardiovascular Physiology and Metabolism
William Harvey Research Institute
Queen Mary University of London, London, UK.
AbstractTo anyone who understands evolution, the reason for this apparent special ability of the naked mole rat is because its lifestyle has created an environment for it that is frequently depleted in oxygen and has a high level of carbon dioxide due to a colonial existence underground in poorly-ventilated tunnels and chambers, so there is evolutionary pressure on them to evolve mechanisms for mitigating the adverse effects of those environmental conditions. The colonial, underground lifestyle and the adaptations to it, would have co-evolved over time to arrive at the present situation.
The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse). We identify metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α is observed while downstream hypoxia responsive-genes are down-regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts show reduced succinate levels during ischemia compared to C57/BL6 mouse and negligible tissue damage following ischemia-reperfusion injury. These evolutionary traits reflect adaptation to a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span.
Introduction
Naked mole rats (Heterocephalus glaber, NMRs) are characterised by their social insect-like (eusocial) behaviour defined by a reproductive division of labour, overlapping generations, and cooperative care of the young. They exhibit a suite of adaptations to living in a hypoxic (low oxygen, O2) subterranean environment1. The NMR (Fig. 1A) is one species within a clade of >30 species of African mole-rats, all of which adopt a subterranean lifestyle across sub-Saharan Africa within differing soil types and degrees of sociality (from solitary to eusocial, Fig. 1B, C)2,3,4,5,6,7. Cooperative breeding and eusociality have evolved convergently within the African mole-rat clade. However, the NMR’s ancestral lineage diverged from their common ancestor ~30 million years ago8. Despite similarities in their subterranean lifestyle, it is accepted that NMRs have many unique aspects to their biology compared to other African mole-rat species1.Up to 300 NMRs live together in an extensive complex composed of labyrinths of underground tunnels, toilet chambers, and a communal nest dug in fine, hard-packed soil, foraging for their staple diet of roots and tubers. Characteristically, mole-rats huddle together in nest chambers that are often many metres distant from transient molehills, which open to the surface and can be up to 0.9 m deep9. In this environment oxygen (O2) regularly becomes scarce and carbon dioxide (CO2) levels become elevated10,11. Out of all the species of African mole-rats, the potential for hypoxia as well as CO2 accumulation is greatest in NMRs as they have the longest cumulative burrow length (up to 3-4 km total tunnel length), the largest absolute group sizes and colony biomass that exceeds other mole-rat species (Fig. 1C)2,3,,4,5,6,7. Collectively, these living conditions limit NMRs gaseous exchange with the surface world. While data on O2/CO2 levels in wild NMR burrows is limited11 and has never been measured in a nest chamber full of animals, NMRs in captive colonies are able to tolerate hours of extreme hypoxia (5% O2 for up to 300 minutes), and can even survive up to 18 minutes of anoxia12. NMRs often elect to spend more time in areas of their burrow system with extreme atmospheric conditions including the nest chamber, where they may spend up to 70% of their time13. This is something not regularly seen in other social African mole-rat species.Fig. 1: Phylogenetic relationships and social status of African mole-rats, the mouse and the hottentot golden mole.A Naked mole-rats (Heterocephalus glaber) from the captive colonies at Queen Mary University of London. B Simplified molecular phylogeny for the African mole-rats indicating main clades/genera and species sampled in this study, together with the mouse Mus and the hottentot golden mole, Amblysomus hottentotus. Mole-rat phylogenetic relationships are based on mitochondrial 12 S rRNA and cytochrome-b sequence data, and analysis of 3999 nuclear genes. Numbers on internal nodes represent approximate divergence times in millions of years ago (myr)10. C Social lifestyles, mean and maximum social groups sizes, and mean biomass of animals per burrow as indicated2,3,4,5,6,7.
This challenging hypoxic habitat creates strong selective pressures and has driven the evolution of unique adaptive traits in NMRs. Mammalian cells are not usually hypoxia-resistant, requiring uninterrupted O2 availability for survival. Fluctuations in O2 availability can lead to ischaemia/reperfusion injury and irreversible organ damage such as is observed following a heart attack14. Given the absence of cardiovascular disease in NMRs15,16,17,18, despite regular fluctuating exposure to hypoxia/anoxia and normoxia, NMR hearts appear to have evolved resistance to both reduced O2 availability and ischaemia/reperfusion (I/R) injury. NMR metabolism has unusual features, such as the ability to switch from glucose to fructose-driven glycolysis in the brain during anoxia12. However, the mechanisms that underpin the extraordinary physiological adaptation to limited O2 availability in the heart are unknown. To determine how these adaptations arise in NMR, we hypothesised that comparison to other African mole-rat genera would enable us to infer the changes in gene expression and metabolic signatures that contribute to the extreme hypoxia tolerance, resistance to cardiovascular injury, and longevity of NMRs.
To do this, we performed RNAseq, metabolomics and pathway enrichment analysis on cardiac tissue from NMR (Heterocephalus glaber) and from seven other African mole-rat genera, Cape mole-rat (Georychus capensis), Cape dune mole-rat (Bathyergus suillus), Common mole-rat (Cryptomys hottentotus hottentotus), Natal mole-rat (C. h. natalenesis), Mahali mole-rat (C. h. mahali), Highveld mole-rat (C. h. pretoriae) and Damaraland mole-rats (Fukomys damarensis) representing differing burrow and soil types, degrees of sociality, lifespan and hypoxia tolerance.
Morphological and life history characteristics of the African mole-rat genera used in this study are summarised in Supplementary Table 1. In addition, we include the evolutionarily highly divergent Hottentot golden mole (Amblysomus hottentotus), an Afrotherian subterranean, solitary mammal. The African mole-rats and the Afrotherian clade last shared common ancestry around 100 million years ago8 (Fig. 1B). Therefore, the golden mole outgroup comparison should highlight similar adaptations to the subterranean niche. Moreover, the Hottentot golden mole is sympatric with Cryptomys and can sometimes utilise their abandoned burrows, thus offering an outgroup that is subject to similar environmental conditions.
We show that unique cardiac metabolic and genetic features characterise the NMR heart compared to other African mole-rat genera and also to evolutionarily divergent mammals, which result in tolerance to hypoxia/anoxia and also lead to negligible tissue damage by I/R injury. These adaptations include supra-physiological glycogen content providing a readily available biochemical energy source via carbohydrate catabolism during anoxia/hypoxia, enhanced intracellular energy reserves (via increased creatine), and constitutive stabilisation (i.e., non-degradation) of HIF-1α under normoxic conditions. In addition, they show reduced succinate levels post ischaemia, which is a key metabolic driver of reactive oxygen species (ROS), and lower lactate production. NMRs express genetic adaptations at the mitochondrial level, which help to dampen ROS-related damage caused by fluctuating environmental O2 availability.
Humans, on the other hand, have never normally lived in an environment in which oxygen can become depleted to that extent, so there has been no evolutionary pressure to adapt to it.
For a supposedly omnibenevolent, omniscient, intelligent designer however, the only reason not to give humans the same ability to survive a period of cardiac muscle anoxia when it had given that ability to naked mole rats can only have one interpretation - it chose not to give it to us but to let us die from heart attacks or be severely disabled by them.
This is just one of the many ways we can tell that an omnibenevolent, intelligent designer wasn't responsible for the present 'design' of human beings and naked mole rats, but a mindless natural process, working without a plan was. It also illustrates that, contrary to creationist mythology, human beings are not some notional supreme achievement nor the apex of an evolutionary process that was 'designed' to evolve us.
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Heart attacks and heart defects torture and kill humans and numerous mammals and birds. The Naked Mole Rat is an exception. What is special about the Naked Mole Rat that the creator has given it this protection? Why don't humans, other mammals, and birds have this protection against heart attacks? It doesn't make sense.
ReplyDeleteThe blood vessels in the body be it veins, arteries, and capillaries, are so excessive, redundant, and overdone there's bound to be defects and flaws and it's inevitable that things are going to go wrong sooner or later. The creator likes to create but is careless, sloppy, incompetent and didn't care about perfecting His creation and didn't care about doing a good job and doesn't care about preventing suffering. The creator is blind as in mentally blind and morally blind, amoral, pitiless, merciless, heartless, indifferent and cruel, and almost certainly insane and malevolent.The creator gave humans and many species of animals defective, flawed bodies and put us in a defective, flawed super dangerous world. This is evidence for stupid design and especially malevolent design.
There are also serious defects and flaws with the brains of humans and many species of animals with stroke, aneurysm, epilepsy, seizures, migraine headache, etc. How cruel to inflict or allow these horrors. The creator is an incompetent idiot, insane lunatic, or malevolent monster who has no conscience. It's a disgusting reprehensible being. The creationists ought to be embarrassed.