New nucleotide discovered in mouse brain

Turns out life has more essential building blocks to play with than previously thought: researchers at Rockefeller University have discovered a new nucleotide in the mammalian DNA code. Remember good ol' adenine, thymine, guanine and cytosine? Well, the alphabet of our DNA sequence is about to receive a new letter. Meet 5-hydroxymethylcytosine; we aren't sure what it does or where it's located, but we know it's important -- really important.

In the announcement, Nathaniel Heintz, director of the molecular biology lab that conducted the research, was exuberant about the significance of the finding: "This is another mechanism for regulation of gene expression and nuclear structure that no one has had any insight into. I think this finding will electrify the field of epigenetics."

Epigenetics, or the study of heritable traits that occur without changes in DNA sequence, pioneered the discovery of a fifth nucleotide, 5-methylcytosine (5-mC), and now it adds a sixth. Since genes alone cannot account for the stark differences among mammals -- all which share a sizeable amount of genetic material -- scientists believe the differentiation stems from a dynamic regulation of gene expression rather than the gene sequence alone. Which is why the discovery of a new nucleotide is so remarkable: it may prompt DNA demethylation, or help regulate gene expression.

Even more remarkable is that the discovery was an act of serendipity. According to Skirmantas Kriaucionis, a postdoctoral associate in the Heintz lab, "We didn't go looking for this modification. We just found it." Kriaucionis was investigating the levels of 5-methylcytosine in two different brain neurons (Purkinje cells and granule cells) and while analyzing the epigenetic makeup of these cells discovered a significant amount of an unknown nucleotide.

Kriaucionis performed several tests to determine the elemental composition of the unknown substance and all tests converged on one result: 5-hydroxymethylcytosine, a nucleotide previously found only in bacterial viruses, which he found "abundant in the mouse and human brain." The next step is to deduce the genetic location, role, and effects of the new nucleotide, believed to have a link to brain function.

[Via EurekAlert]

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9 Comments

I don't understand. We've sequenced mouse genomes thousands of times before, how have we never noticed? Does this nucleotide not exist in the actual genome, but is free-floating in the cell? Or does this nucleotide appear like one of the traditional 4 when we run sequencing tests? Can anyone help me out?

5-hydroxymethylcytosine is the methylated form of cytosine, not a new nucleotide.

So this nucleotide would still code for the same amino acid if it was in the genetic sequence? Why is this so groundbreaking as : the reason why humans and other animals are so different?

Methylation is an epigenetic factor. Epigenetics is the study of factors that influence how our DNA is read and processed, w/o directly affecting the code itself. The methylation of the parent can affect what genes are expressed in offspring. Look up epigenetics on wikipedia for a bigger explanation; which popsci should have done before posting this incredibly wrong article.

5-hydroxymethylcytosine is different from methylated cytosine. While it has been long known to exist in bacteriophage DNA, it was surprising to find in human DNA. It would not be detected by normal sequencing methods. It was noticed when they consistently observed a significantly lower amount of methylated-cytosine in their Purkinje DNA samples and the presence of a unidentified spot on their thin-layer chromatography plates. hdmC was found to comprises 0.6% of total nucleotides in Purkinje cell DNA, 0.2% in granule cells, and is not present in cancer cell lines. It is nearly 40% as abundant as methylated-C in Purkinje cell DNA. I is enriched in the brain, suggesting a role in epigenetic control of neuronal function.

Really misleading and sensationalist article. It's not a new "building block" because the change to the nucleotide (the extra hydroxymethyl group) only occurs in certain genes in certain cells (neurons in this case). It's not something that's part of the DNA that will be passed on to offspring. Epigenetic modifications like this occur in all animals.

Also, from the tiny amount of googling I did it looks like the same form of cytosine was found in rat, mouse, and frog brains as early as 1972 (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1178489).

These are accurate comments.

Claiming this is a new Neucleotide is analagous to a situation in which there are only 4 types of bread in the world: Wholemeal, Rye, Pitta and Naan, and someone claims that they've discovered a new kind of bread called Wholemeal With Peanut Butter.

I think the key here is that differences is the genome as classically described are not the only factors in gene expression, the presence of other similar nucleotides can be responsible for the differing traits seen that cannot be explained through other genetic or environmental differences. Also if these nucleotides are not part of the classic genome, who knows how they are inherited and how we may be able to control the expression of traits spotted in the genome by applying these nucleotides. Sounds very interesting to me.

hey guys quit baggin on this intriguing discovery! yeah i would call leading the witness on this author for the wacky and wild claims of a new DNA base pair (ACGT... yeah girl you did do it). but its still cool that we may be uncovering how regulation might explain why humans are so different bananas even while we share a fair able amount of code! this is like where people are finding species differentiation cant be credited only towards sequence change. i just read different nuclear envelope pores help regulate genes in different human tissues. kinda on the same subject but look it up if you found this interesting :)



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