Wednesday, 21 September 2016

Human DNA Radiation Tolerance is Increased by the Unique Protein in Water Bears (Tardigrade)

In my 2010 lecture on the search for extraterrestrial life, I had discussed how some animals are known to survive extreme conditions of heat, radiation, pressure, vacuum etc. This is important because tolerance of such extreme conditions would indicate that life might have evolved even on planets which are on the periphery of the habitable zones. I reproduce a few slides from my lecture in the following:

It is clear that these species have evolved to withstand some of the most inhospitable environments imaginable. 

Tardigrade or Water Bears or moss piglets are one of the hardiest of animals.  They are tiny (0.05 to 1.2 mm long) and live near water. In adverse conditions of extreme hot or cold, very high pressures, space vacuum or intense UV/X-ray radiation water bears shrink, dehydrate and put metabolic activity on hold.  Dehydrated water bears can survive for years but come back to life when in contact with water which they need to grow and reproduce. 

The question is - how do they manage to survive the extreme conditions?  Such unusual tolerance of tardigrades has long fascinated researchers; however, the molecular mechanisms enabling such exceptional tolerance have remained largely unknown.  Water Bears Video
A study of tardigrade genome, published in Nature Communications this week has provided some amazing insight into the tolerance of tardigrade to extreme conditions.
I am reproducing their conclusions in the following slide.  (Apologies for the somewhat formal language of the slide but I feel it presents the researchers' conclusions in a pristine way)
What I find the most exciting is the demonstration that the unique proteins can also protect human cells against X-rays induced DNA damage and improve human tolerance to radiation.  This is a game-changer and as the authors say, there could be a bountiful source of protection genes and mechanisms.  

An interesting question to ask is how did R. varieornatus tardigrade acquire the genes for the unique protein - Hashimoto et al. call the protein Dsup (damage suppressor). 
This has been a controversial issue with some previous work suggesting that tardigrade acquired many of their genes from bacteria through a process called horizontal gene transfer (HGT) - an important mechanism for the evolution of many organisms.  This study - which is by far the most extensive and is a full genome sequence of a tardigrade - sets an upper limit of 1.2% on the contamination by foreign genes and claim that the protein Dsup is uniquely developed by the tardigrade itself.  
It was also demonstrated that Dsup protein affords DNA protection without impairing cell viability and is suitable for application to confer tolerance to other animal cells
In fact, Dsup-expressing human cultured cells exhibited better tolerance to 4 Gy of X-ray radiation. (One gray or Gy is the absorption of one joule of energy, in the form of ionizing radiation, per kilogram of matter). 

In humans, a whole-body exposure of 5 Gy of ionizing radiation usually leads to death within 14 days.  R. varieornatus exhibited far superior tolerance of up to 4000 Gy of helium ion beam in adults. There may be additional factors besides Dsup in the tardigrade genome that contribute to their exceptional tolerance. This, of course, requires further research.

Tardigrade also have extreme tolerance to other environmental stresses like heat, vacuum, high pressures etc.  They deal with it by dehydratings themselves - going into a dessicated state. As desiccation causes severe oxidative stress (see slide below), desiccation tolerant animals should have the ability to mitigate this type of stress. Multiple gene repertoire traits in the tardigrade genome suggested enhanced tolerability against oxidative stress.

I have found this work very exciting - as I have said previously  - because of the promise that the genome sequence and gene repertoire of the extreme-tolerant tardigrade provide a treasury of genes to improve or augment the tolerant ability in stress-sensitive animal cells (that includes humans too!).

Why did tardigrade acquire genes to make Dsup?

Tardigrade are water-dwelling micro-animals.  Because of their extremotolerance they are found everywhere imaginable - from rain forests to the Antarctic and from high mountains to deep oceans.  But the question remains - why did tardigrade acquire such extreme tolerance to their surroundings.  

Professor Kunieda, University of Tokyo made the following comment on this question:

'I (and many researchers) suppose that these extremotolerance are likely a side product of adaptation to desiccation (dehydration).  Dehydration is common environmental stress to terrestrial organisms and causes  severe damage on various biomolecules. Some of these damage, for example DNA breaks, are also caused by radiation. Thus, adaptive mechanism to dehydration may enable tolerance to radiation, which is mostly artificial stress. The extremes other than radiation can be tolerated by tardigrades only in the dehydrated state. The dehydrated tardigrades exhibit no sign of life activity (are ametabolic) and are almost chunk of biomolecules (not living organisms;
this state also called as cryptobiosis, a hidden life). They tolerate various extremes including open space as a chunk of biomolecules and after exposure, they can resume activity upon rehydration. The ability to enter dehydrated state
is the key for the extremotolerance' 

Final Word:  Evolution continues to throw surprises. Tardigrade are tiny animals but have evolved to be robust ready to handle almost any eventuality.  If we can copy some of the gene expression to humans then may be many diseases can be cured or prevented from happening. Obviously, this work is a first step in understanding how we can have much more robust biological systems - lot more research needs to be done to understand that.

This type of result must be read by those who want any research money to be spent on projects that yield economic benefits in the shortest time span possible.

Finally, I hope the blog piece was not too difficult to read.  I have tried to provide links for more explanation. But do read my talk about extraterrestrial intelligence

16 March 2017 news:  
I am grateful to Professor Kunieda for his valuable comments and allowing me to use material from their paper; and also making available supplementary information that, as a retired physicist, I found immensely useful.
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