Saturday, November 02, 2024

Water bear genes provide protection from radiation damage

Amazing stuff!

"A newly described species of tardigrade (Hypsibius henanensis) is giving scientists insights into what makes these tiny eight-legged creatures so resistant to radiation. Scientists sequenced the genome of this new species and identified thousands of genes that become more active when exposed to radiation. These processes point to a sophisticated defence system that involves protecting DNA from the damage that radiation causes and repairing any breaks that do occur. They hope that these insights could be harnessed to protect humans exposed to radiation during space missions or to improve cancer treatment."

"... One of the genes, called TRID1, encodes a protein that helps to repair double-strand breaks in DNA by recruiting specialized proteins at sites of damage. “...

The researchers also estimate that 0.5–3.1% of the tardigrade’s genes were acquired from other organisms through a process known as horizontal gene transfer. A gene called DODA1, which seems to have been acquired from bacteria, enables tardigrades to produce four types of antioxidant pigments called betalains. These pigments can mop up some of the harmful reactive chemicals that radiation causes to form inside cells, which account for 60–70% of radiation’s damaging effects. ..."

From the editor's summary and abstract:
"Editor’s summary
Tardigrades are small invertebrates renowned for their resistance to harsh environmental conditions, including ionizing radiation that would kill many organisms. Li et al. now describe a previously unknown species of tardigrade, Hypsibius henanensis, and investigate how these organisms respond to radiation treatment using genome, transcriptome, and proteome analyses. The mechanisms include induction of biosynthesis of betalain pigments and up-regulation of both tardigrade-specific and more widely distributed pathways for stress response and DNA damage repair. ...
Abstract
INTRODUCTION
Tardigrades, commonly known as water bears, are small ecdysozoans renowned for their tolerance to extreme environments, including ultrahigh radiation. They exhibit exceptional resistance to ionizing radiation, withstanding doses as high as 3000 to 5000 grays (Gy) of gamma rays, which is ∼1000 times the lethal dose for humans. The mechanism of radiotolerance in tardigrades remains largely unclear.
RATIONALE
A multi-omics data mining strategy holds immense potential for unraveling the mechanisms of extreme environmental tolerance in tardigrades. By integrating genomics, transcriptomics, and proteomics, we decipher the genome-wide landscape of antiradiation response. After differential analysis and screening of key molecules, we used biochemical and cellular methodologies to validate their functional roles and delve into the underlying molecular mechanisms.
RESULTS
We obtained a well-annotated chromosome-level genome of a radiotolerant species, Hypsibius henanensis sp. nov., newly identified in this study. Through differential analysis of transcriptome and proteome after heavy ion radiation, we identified 2801 differentially expressed genes (DEGs). On the basis of evolutionary and functional analyses of these DEGs, we characterized the radiotolerance mechanisms from three different perspectives:
First, horizontal gene transfer (HGT) may be an important evolutionary event that substantially contributes to the development of tardigrades’ ultrahigh radiation resistance. We identified a DOPA (dihydroxyphenylalanine) dioxygenase gene, DODA1, that we propose is a product of HGT from bacteria to tardigrades. DODA1 is responsive to radiation and confers radiation resistance through biosynthesis of betalains, a kind of pigment that exists mainly in plants, a few fungi, and bacteria. Next, we found that a tardigrade-specific radiation-induced disordered protein, TRID1, accelerates DNA damage repair by means of a process that encompasses phase separation.
Lastly, non-tardigrade-specific genes also contribute to the tardigrades’ radiotolerance. We found that two mitochondrial respiratory chain complex assembly proteins, BCS1 [ubiquinol–cytochrome c reductase (bc1) synthesis] and NDUFB8 [NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8], are pronouncedly up-regulated and then accumulate to accelerate NAD+ (nicotinamide adenine dinucleotide) regeneration for poly(adenosine diphosphate–ribosyl)ation (PARylation) and subsequent PARP1 [poly(adenosine diphosphate–ribose) polymerase 1]–mediated DNA damage repair.
CONCLUSION
Through multi-omics data mining and functional validation, our work uncovers a role for DODA1 in activation of an amino acid metabolism pathway (tyrosine-DOPA-betalains axis) for reactive oxygen species mitigation, elucidates tardigrade-specific TRID1-mediated phase separation in contributing to radiotolerance by enhancing double-strand break repair efficiency, and provides insight into the participation of BCS1 and NDUFB8 in acceleration of mitochondrial oxidative phosphorylation and NAD+ regeneration. Functional research on these radiotolerance mechanisms of tardigrades will broaden our understanding of cell survival under extreme conditions."

Nature Briefing: Cancer

New species of tardigrade reveals secrets of radiation-resisting powers "Knowing the genes responsible for water bears’ radiation tolerance could lead to diverse applications, from cancer treatment to space exploration."




Schematic of mechanisms that confer radiotolerance to H. henanensis sp. nov.


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