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Sixth DNA base discovered?

sciencedaily.com

11–20 of 40 posts

Re: Sixth DNA base discovered?

#11
post #2

"In the early 80s, to these four "classic" bases of DNA was added a fifth: the methyl-cytosine (mC) derived from cytosine." How come any biology course or book I've ever seen, whether high-school or top-university level, only teaches about four bases?

I think that this article is somewhat misleading. In terms of replication, heritability, RNA, and protein production, there are only four bases. Adenine matches with Thymine, Cytosine matches with Guanine. As Watson and Crick so famously understated in their seminal paper, 'It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.'

When DNA is replicated, methyl-cytosine pairs with guanine just like cytosine does. The only way to maintain the 'methylation marks' is to add a methyl group back on to the newly synthesized cytosine. When DNA is converted into RNA, which is then converted into protein, whether a cytosine has a methyl group attached makes no difference to the final protein.

So whether a cytosine is methylated or not doesn't change the DNA sequence you inherit from your parents. It doesn't change the structure of the protein produced from that gene. What it can do, is change when and where that gene is expressed - which can make a huge difference to the behaviour of the cell.

For instance, a gene such as BRCA1 could be 'turned off' because too many cytosines are methylated, and this could cause a cell to become cancerous. Or a lack of methylation could cause too much c-Myc to be produced, which could result in the same outcome. But then, there many other genetic regulatory mechanisms that can do that as well - such as histone modifications, chromatin structure, transcription factors, and probably methyl-adenine too! All these mechanisms interact to ensure genes are turned on and off at the right time and place, and this field is known as 'epigenetics'.

Methyl-cytosine is a modified version of cytosine that is a very important part of epigenetics, but since it is almost irrelevant to other aspects of genetics, I would argue that you could not consider it a 'fifth base'. Having read the paper, methyl-adenine is the same - interesting new aspect of epigenetics and gene regulation, but not a new base. Also, this paper doesn't exactly 'discover' it, we found methyl-adenine in bacteria in the 60s....

If you want to read about truly new bases, scientists actually synthesised an entirely new pair of bases last year, that can replicate and encode RNA and proteins! A seriously cool step forward in synthetic life http://www.nature.com/news/first-life-with-alien-dna-1.15179

Re: Sixth DNA base discovered?

#13

I wonder if the other two bases can be methylated? Though given they are paired to bases that can be methylated... Also, I hadn't heard of methylation being called another base. More of a modifier/marker on the base.

Yes! Bacteria primarily methylate Adenine. [0] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754416/

Re: Sixth DNA base discovered?

#15
post #2

"In the early 80s, to these four "classic" bases of DNA was added a fifth: the methyl-cytosine (mC) derived from cytosine." How come any biology course or book I've ever seen, whether high-school or top-university level, only teaches about four bases?

Because methylcysteine and methyladenine aren't really fundamentally different from their unmethylated counterparts. In terms of the first order information content, they're identical. There differences are as regulatory annotations, but in terms of base pairing they're the same.

I kind of cringed when I read that they are "fifth" and "sixth" base pairs because of the significant functional overlap with two of the existing ones.

Re: Sixth DNA base discovered?

#16

Earlier quoted context omitted.

I don't understand why you wouldn't set that sort of thing out at the basic level, even if it were accompanied with 'we understand ACGT quite well, the others are pretty mysterious and we're not sure if they matter as much.' Seems a bit like teaching English by focusing only on spelling but omitting any mention of punctuation or grammar for the first few years. Of course we don't try to teach that all at once, but ev…

Because it's just not very important at that point. If you covered all the exceptions and special cases in biology, Bio 101 would never end. It'd be kind of like teaching string theory at the same time as F=M*A.

I strongly disagree. You don't have to go into detail about them, but knowing the fact of their existence is fundamental. If you think there are only 4 bases and then later find out that there are others, the first reaction t that is to feel short-changed about your previous education and stupid about all the new stuff you have to absorb. If you are told there's 4 bases that seem to deliver 99.9% of the action and another 20 or so which hardly get a look in, then you have a basic overview of the field.

It'd be kind of like teaching string theory at the same time as F=MA.*

So what? 'All matter is made up of very tiny things called atoms. There are 118 different types of atoms that that we know about, which have many interesting and surprising characteristics. Many atoms can be combined with each other to form molecules. All atoms seem to be made out of different combinations of subatomic particles, which are the very smallest things we have managed to measure, but which we only partially understand. Some scientists think subatomic particles are made out of even tinier structures called strings, but nobody has managed to prove that one way or the other.'

You don't have to give a big long-winded explanation, but there's nothing wrong with sketching out in very general terms where the frontiers of our scientific knowledge lie. Likewise you don't have to teach small children comparative linguistics, but it's a good thing to make them aware early on that there are many different languages that originate in different countries. Not talking about the existence of things when trying to introduce a field really stifles curiosity, by obscuring the fact that that there are many interesting avenues of inquiry that have yet to be explored.

Re: Sixth DNA base discovered?

#17
I am always highly skeptical of Science Daily articles - this one sounds like it was written by someone without further background knowledge than what was given in a press release. Or, worse, this person far overstated what the cited researchers claim

I think the 'layperson' summary of this article should be that the authors may have found an unappreciated mechanism for gene expression [1-3; 3 articles were published simultaneously].

As you may have heard, your genome comprises four 'letters', called the DNA bases. Collections of these bases called genes encode proteins, molecular structures that perform myriad functions. Indeed, everything that you can see on a living organism is either protein or was created by a protein.

Genes have specific functions that are often limited in both time and space - the protein encoded by a gene may only be needed in the embryonic pancreas, for example. In the field of epigenetics, researchers try to understand the causes of this tight control of gene activity, among other things.

The addition of methyl groups to DNA bases is a long appreciated way to control gene activity - see ref. 4, which is an excellent, freely available cell biology text. The DNA base cytosine is often modified to yield methyl-cytosine, a methylated base with a well established role in the regulation of gene expression; methyl-cytosine tends to mark genome areas with lower probabilities of gene expression.

The authors find that methyl-adenine seems to play a role opposite to methyl-cytosine, surprisingly. While the existence of methyl-adenine was known in bacteria, its function in gene expression in more complicated organisms was not known. Refs 1-3 don't show a causative role for methyl-adenine in increasing gene expression but the correlations the authors report are likely to be followed up.

In summary, the story behind this article is pretty exciting and could indeed expand our understanding of epigenetics, cell biology and perhaps more.

One should remain extremely skeptical of anything in Science Daily - always go to the source.

[1] http://www.sciencedirect.com/science/article/pii/S0092867415...

[2] http://www.sciencedirect.com/science/article/pii/S0092867415...

[3] http://www.sciencedirect.com/science/article/pii/S0092867415...

[4] http://www.ncbi.nlm.nih.gov/books/NBK26854/

Re: Sixth DNA base discovered?

#18
post #2

"In the early 80s, to these four "classic" bases of DNA was added a fifth: the methyl-cytosine (mC) derived from cytosine." How come any biology course or book I've ever seen, whether high-school or top-university level, only teaches about four bases?

Because methylcysteine and methyladenine aren't really fundamentally different from their unmethylated counterparts. In terms of the first order information content, they're identical. There differences are as regulatory annotations, but in terms of base pairing they're the same. I kind of cringed when I read that they are "fifth" and "sixth" base pairs because of the significant functional overlap with two of the ex…

> Because methylcysteine and methyladenine aren't really fundamentally different from their unmethylated counterparts...

You mean methyl-cytosine; methyl-cysteine would be a derivative of the amino acid cysteine.

Re: Sixth DNA base discovered?

#19

Earlier quoted context omitted.

Because it's just not very important at that point. If you covered all the exceptions and special cases in biology, Bio 101 would never end. It'd be kind of like teaching string theory at the same time as F=M*A.

I strongly disagree. You don't have to go into detail about them, but knowing the fact of their existence is fundamental. If you think there are only 4 bases and then later find out that there are others, the first reaction t that is to feel short-changed about your previous education and stupid about all the new stuff you have to absorb. If you are told there's 4 bases that seem to deliver 99.9% of the action and an…

> If you are told there's 4 bases that seem to deliver 99.9% of the action and another 20 or so which hardly get a look in

How many blood types are there? Most people will say 4 (or 3, or 2 depending on how you define it). But there are actually far more of them, but the rest are rare or less important.

Re: Sixth DNA base discovered?

#20

Earlier quoted context omitted.

Because it's just not very important at that point. If you covered all the exceptions and special cases in biology, Bio 101 would never end. It'd be kind of like teaching string theory at the same time as F=M*A.

I strongly disagree. You don't have to go into detail about them, but knowing the fact of their existence is fundamental. If you think there are only 4 bases and then later find out that there are others, the first reaction t that is to feel short-changed about your previous education and stupid about all the new stuff you have to absorb. If you are told there's 4 bases that seem to deliver 99.9% of the action and an…

I strongly agree with you -- if you're learning on your own you often need to know that something exists (and usually need to know the term for it) to be able to lookup / research.
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