You may have billions and billions of good reasons for being unfit

Mitochondrial RNA sequence variation across a large number of individuals. Credit: Awadalla Lab

Although our chromosomes are relatively stable within our lifetimes, the genetic material found in our mitochondria is highly variable across individuals and may impact upon human health, say researchers at the University of Montreal and its affiliated CHU Sainte-Justine Hospital.

Genomes are changing, not just from generation to generation, but even and in fact within our . The researchers are the first to identify the extent to which the editing processes of RNA code can vary across a large number of individuals. "Mitochondria are the of our cells, and the more power a cell needs, such as a muscle cell, the more it has. Mitochondria are organelles in our cells with their own , separate from the DNA in our chromosomes, and the many mitochondria in the same individual can have different genetic mutations," explained Alan Hodgkinson, who is first author of the study. "The many mitochondria in the same cell can have different genetic mutations. Our research helps us to understand how variable mitochondrial RNA processing can be and what the possible consequences of that might be on health." By way of example, the researchers have found an association between the level of modification of RNA and our – the rate at which we are able to convert food into energy to power our bodies. The findings add extra layers of complexity to our understanding of how genetics influence our health.

The study was made possible thanks to the participation of nearly 40,000 Quebecers in the CARTaGENE initiative. CARTaGENE is one of the world's most comprehensive banks of genetic information: in addition to , participants share their health history, residential information, ethnicity, languages spoken and their family history of disease. Philip Awadalla is Director of the CARTaGENE initiative and lead author of the study. "The people of Quebec want to take part in science," he said. "This program is unique in the world. Other initiatives are taking place, but they aren't as comprehensive. Elsewhere, researchers are able to recruit 5% of the people they invite. Quebecers' collaboration rate is five times that." CARTaGENE's data and samples are available to the local and international research community.

The researchers looked specifically at mutations in the RNA of the mitochondria. If DNA is the printing press that determines the functions of a living organism, RNA is the print that it leaves behind. And just like with a printing press, sometimes the print (known as transcription) is slightly different from the press. "We looked at the variation within and across individuals in the mitochondrial RNA. This is the first survey of mitochondria-wide RNA variation at a population level," Hodgkinson explained. "We used the data of 1,000 participants in the CARTaGENE initiative, making this the largest RNA sequencing in the world to date. With this kind of depth of information, we've identified a vast array of fine-scaled differences not just between individuals but also within individuals – and that's the power of the data. But within that, we focused on one specific signature that we found really interesting – the signature in the sequencing data that represents the modification of RNA at important sites." "The other world first here is an unprecedented level of resolution – we're not only capturing change happening at the DNA level, now we're capturing "epiphenomena" happening at the RNA level. We can compare across individuals to see how variable different individuals are within themselves," Awadalla added.

Many other factors are at play in determining the variation in the transcription of mitochondrial RNA. "Your DNA is mostly found in the nucleus of each cell, and there is interaction between products from the genome of the nucleus and the genome of the mitochondria to create cellular energy – they're not completely separate," Hodgkinson explained. "We find an association between variation in a nuclear gene – the DNA that's from your chromosomes – with the level of modification in the mitochondrial RNA. The resulting modifications may impact cellular energy production, but there is much more work to be done to confirm and fully understand these processes".

While the mechanisms at work in our body may offer couch potatoes a handy excuse, the actual outcomes in terms of our health may not be deterministic. "It makes sense that we would see an association between mitochondria and metabolism rates, because mitochondria are the power packs of each cell. We have determined that our genome's ability to modify itself is partly hard-wired – the open question is how does our genome react to exposures in the environment?" Awadalla said.

More information: "High-Resolution Genomic Analysis of Human Mitochondrial RNA Sequence Variation," by A. Hodgkinson et al. Science, 2014.

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JVK
2 / 5 (4) Apr 24, 2014
Excerpt: "We have determined that our genome's ability to modify itself is partly hard-wired – the open question is how does our genome react to exposures in the environment?"

The epigenetic landscape becomes the physical landscape of DNA in organized genomes of all species via experience-dependent receptor-mediated changes that enable nutrient uptake. The nutrients are metabolized to species-specific pheromones that control the physiology of reproduction.

Continued use of the term evolution -- as if mutations and natural selection for anything else but nutrients could somehow cause species diversity -- attests to the futility of using outdated ideas in attempts to pretend that they had been validated by experimental evidence of cause and effect.

Ecological variation and ecological adaptations are responsible for species diversity -- all else is theory--and mutation-driven evolution is not even biologically plausible.

JVK
2 / 5 (4) Apr 24, 2014
Neo-Darwinism, the Modern Synthesis and selfish genes: are they of use in physiology?
http://jp.physoc....abstract
"If you learnt evolutionary biology and genetics a decade or more ago you need to be aware that those debates have moved on very considerably, as has the experimental and field work on which they are based."

Physiology is rocking the foundations of evolutionary biology
http://ep.physoc....235.long
"Perhaps the elegant mathematics and the extraordinary reputation of the scientists involved blinded us to what now seems obvious:..."

Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
http://www.ncbi.n...24693353
"THIS MODEL DETAILS HOW CHEMICAL ECOLOGY DRIVES ADAPTIVE EVOLUTION VIA: (1) ecological niche construction, (2) social niche construction, (3) neurogenic niche construction, and (4) socio-cognitive niche construction."
dedereu
5 / 5 (1) Apr 27, 2014
4 billions years of evolution to be alive and not be dead, has given very complex structure of the life that cannot be what we think at first in simple models.
dedereu
not rated yet Apr 27, 2014
It remains to find how theses changes are driven by what we eat, junk or good food over several generations ?
JVK
1 / 5 (1) Apr 27, 2014
It remains to find how theses changes are driven by what we eat, junk or good food over several generations ?


It remains to find out why what is known about how the epigenetic landscape becomes the physical landscape of DNA in the organized genomes of species from microbes to man continues to be ignored.

Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
http://figshare.c...s/994281

"This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding..."
yvchawla
not rated yet Apr 28, 2014
Any objective thing of the world including our body or DNA structure is not the sign of one's being alive. The sign of being alive are 'feeling', and 'naming', thinking. The 'feeling' of friction-'things are okay', 'things are not okay'-is the sign of being alive.
https://sites.goo...ingalive
lymphomasurvival
not rated yet May 17, 2014
We see over several years the remarkable influence of several lifestyle behaviors...optimal vitamin D, regular exercise, quality sleep/stress management, balanced nutrition...on correcting faulty gene expression driving the lymphoma process.

www.LymphomaSurvival.com
JVK
not rated yet May 17, 2014
...correcting faulty gene expression...


may occur when a beneficial nutrient-dependent pheromone-controlled microRNA/messenger RNA balance is restored. Unfortunately, most people do not know the difference between a mutation and a nutrient-dependent single nucleotide polymorphism because they have been taught to believe that mutations and natural selection lead to biodiversity. I often wonder if people like that know that the physiology of reproduction is controlled by the metabolism of nutrients to species-specific pheromones.

anonymous_9001
not rated yet May 18, 2014
...correcting faulty gene expression...


may occur when a beneficial nutrient-dependent pheromone-controlled microRNA/messenger RNA balance is restored. Unfortunately, most people do not know the difference between a mutation and a nutrient-dependent single nucleotide polymorphism because they have been taught to believe that mutations and natural selection lead to biodiversity. I often wonder if people like that know that the physiology of reproduction is controlled by the metabolism of nutrients to species-specific pheromones.



I often wonder when you're finally going to realize that there's a difference between changing sequence and changing expression. How can you still be mixing them up?
JVK
not rated yet May 18, 2014
The anonymous fool often claims that I am confused despite the number of citations to published works that I provide. Here's another one:

Quantitative analysis of RNA-protein interactions on a massively parallel array reveals biophysical and evolutionary landscapes http://dx.doi.org...nbt.2880

Unfortunately, those who cannot comprehend the concept of biophysical constraints will continue to be confused about how the epigenetic landscape is linked to the physical landscape of DNA in the organized genomes of species from microbes to man, because they cannot think in terms of nutrient-dependent pheromone-controlled ecological adaptations.

Like the anonymous fool, they may also think that I am confused about the differences between changing sequences and changing gene expression. Note, however, the anonymous fool and others never tell anyone how mutations enable either natural selection or the evolution of biodiversity. In theory, it "just happens".
anonymous_9001
not rated yet May 18, 2014
Here's another one:

Quantitative analysis of RNA-protein interactions on a massively parallel array reveals biophysical and evolutionary landscapes http://dx.doi.org...nbt.2880


From the abstract:

modeling mutational paths...consequences of sequence-function relationships


i.e., they note how mutations result in functionally different variants and what those variants do.
JVK
not rated yet May 18, 2014
How do the mutations, which perturb the protein folding that links nutrient-dependent changes in seemingly futile changes in RNA to DNA, enable functional variants?

As always, you seem to think that mention of the word "mutations" has some explanatory power.
anonymous_9001
not rated yet May 18, 2014
Mutations don't always perturb folding enough to cause negative changes. Silent mutations are well characterized. You're also ignoring the implications of all the in vitro evolution experiments performed. Tons of work has been done with mutagenesis to improve protein function. The same concept applies in vivo. Some variants do their job better than others. Mutation produces these variants by shuffling genetic information. It's not difficult to comprehend.

As always, you seem to think that mention of the word "mutations" has some explanatory power.


That's rich coming from you who typically thinks the omission of the word in a paper means the authors don't believe in it.