Researchers explain the origin of the mysterious periodicity of the genome

Researchers explain the origin of the mysterious periodicity of the genome
The DNA molecule, formed by a double helix, winds around histone molecules twice, thus forming nucleosomes. The pink regions indicate those enriched in Adenine/Thymine base pairs. Credit: Iris Joval Granollers

Scientists at the Institute for Research in Biomedicine (IRB Barcelona) have found an explanation for a periodicity in the sequence of the genomes of all eukaryotes, from yeast to humans. The results published in the journal Cell offer an alternative explanation to the one based on natural selection, which has been accepted by the scientific community to date.

The researchers demonstrate that DNA damage and repair processes can play a role in the generation of sequence periodicity in the genomes of eukaryotic organisms. These processes are influenced by the orientation of the DNA structure when this molecule is packaged inside the cell nucleus, thus favouring a certain composition with a periodic nature in eukaryotic genomes.

"The answer we provide allows a better understanding of why our and that of other species have developed into what they are today," says Núria López-Bigas, head of the study and leader of the Biomedical Genomics lab at IRB Barcelona.

The "mysterious" periodicity of the genome

Since the sequence of the and that of other organisms such as the mouse and fruit fly became known at the beginning of the 21st century, some researchers have noted a marked periodicity in the proportion of comprising adenine (A) and (T). Indeed, the proportion of A/T pairs has been observed to be greater every 10 base pairs.

This periodicity has been associated with how DNA winds around nucleosomes (the simplest compaction form of DNA, in which it envelopes proteins called histones). The explanation given has been that natural selection would favour the appearance of A/T bases as these bases would provide the DNA structure with a greater degree of flexibility, thus allowing it to wind around histones to form nucleosomes.

Tumour mutations provide the key

By studying the distribution of in more than 3,000 human tumours, the team at IRB Barcelona observed that the mutations also accumulated every 10 DNA base pairs.

"By examining mutation distribution along the genomes in regions in which we ruled out the presence of selection, we found a marked periodicity of 10 base pairs in the DNA that forms part of nucleosomes," explains Oriol Pich, Ph.D. student and awardee of a fellowship from the Barcelona Institute of Science and Technology (BIST) and first author of the paper.

The periodicity of mutations occurs because the structure of the DNA packaged inside the nucleosome favours the appearance of regions that are prone to damage and to repair. Consequently, these regions are more susceptible to mutations.

Next, the researchers turned their attention to mutations that are passed from one generation to another, in both humans and plants. They found that these hereditary mutations also accumulated every 10 base pairs.

With this new discovery of how nucleosomes affect DNA mutations, the researchers deduced that it could also explain the development of the mysterious periodicity of the sequence of eukaryotic genomes.

Mutations over millions of years of evolution

The scientists at IRB Barcelona hypothesised that, as most mutations that we get are in cytosines (C) that convert into thymines (T), most of those regions most prone to mutating over millions of years have become A/T base pairs.

To test this notion, the researchers performed a mathematical simulation of genome evolution and demonstrated that the periodicity of the sequence of the human genome and that of other eukaryotes could have arisen from the periodic rate of mutations.

"We are really pleased to provide the scientific community with this alternative explanation regarding periodicity," say Oriol Pich and Núria López-Bigas, who highlight the importance of this kind of research. "It is basic knowledge derived from curiosity-driven research that allows us to achieve a better understanding of nature."

However, the results of the study are not only a breakthrough regarding current understanding of the human genome but they also explain how tumours acquire mutations. This knowledge is relevant for identifying mutations that are relevant for tumour development—another field of expertise of López-Bigas' group.


Explore further

DNA correction mechanism is more efficient in the most important regions of the genome

More information: Oriol Pich et al. Somatic and Germline Mutation Periodicity Follow the Orientation of the DNA Minor Groove around Nucleosomes, Cell (2018). DOI: 10.1016/j.cell.2018.10.004
Journal information: Cell

Citation: Researchers explain the origin of the mysterious periodicity of the genome (2018, November 2) retrieved 22 September 2019 from https://phys.org/news/2018-11-mysterious-periodicity-genome.html
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Nov 05, 2018
Once one inserts the words "millions of years" and "evolution" into one's research, the conclusions drawn from it becomes highly suspect since we did not "evolve" from a original ancestor as currently supposed. Darwinian evolution (from one kind into another kind) is simply not possible - for various mathematical and genetic reasons.

Nov 05, 2018
Fred, you excel at being vacuous.

Nov 05, 2018
Hey fred maybe it's like this thing

"The Bible code (Hebrew: הצופן התנ"כי‎, hatzofen hatanachi), also known as the Torah code, is a purported set of secret messages encoded within the Hebrew text of the Torah. This hidden code has been described as a method by which specific letters from the text can be selected to reveal an otherwise obscured message."

-gods word is everywhere ya know.

Nov 09, 2018
@fred
the conclusions drawn from it becomes highly suspect since we did not "evolve" from a original ancestor as currently supposed
except DNA proves you wrong
more to the point: have you ever actually seen the different stages of development of a human baby?
No?
thought so...
Darwinian evolution (from one kind into another kind) is simply not possible - for various mathematical and genetic reasons
then why are there absolutely zero studies validating this claim?

and why are there multiple studies proving you wrong?

1- look up the scientific method - https://en.wikipe...c_method

2- use it

3- and again, just to prove you wrong, and to note you have *yet* to actually refute with the same level of evidence: http://www.talkor...comdesc/

.

@otto
LMFAO

Nov 09, 2018
@ottoyukyukyuk
Yeah sort of like sagan's 'first contact' book/jodie foster movie, when they figured pi out to gazillions of places they found all these messages.

Maybe one day we'll decode our genome and find 'about religion - I wasnt actually being serious dude' or something deep inside there. I dunno.

Hey - maybe they'll find all this undeniable evidence that its artificial... complete with misspells and redactions. That would be fun.

Nov 09, 2018
Hey - maybe they'll find all this undeniable evidence that its artificial... complete with misspells and redactions. That would be fun.

You talkin' bout the bible or DNA?
Cuz DNA is full of them... :-)

Nov 09, 2018
Once one inserts the words "millions of years" and "evolution" into one's research, the conclusions drawn from it becomes highly suspect since we did not "evolve" from a original ancestor as currently supposed. Darwinian evolution (from one kind into another kind) is simply not possible - for various mathematical and genetic reasons.

Please show us that math or a genetic research paper that makes your statement true...


Nov 10, 2018
You talkin' bout the bible or DNA?
Cuz DNA is full of them... :-)
I'm talking about intelligent design by a superior but faulty alien entity.

Are we research? Hobby? Companionship?

IF we were created, either from scratch or from the DNA of our closest natural relatives who just happened to possess the most appropriate form for tool making and weapons wielding, then we might expect to find evidence of such tinkering in our DNA.

Because perfection cannot exist in the corporeal world.

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