The worlds most famous living biologist, Casey Luskin, is either an IDiot, or the biggest IDiot in the known universe.
Being an expert in molecular biology, Casey has previously discussed Junk DNA, ie ERVs, at his blog ‘Evolution News and Views’. Now hes written a blog post on this paper about Junk RNA:
Larry covers all the bases nicely. Now I know, as a fact, Casey does not understand this paper. I know he didnt even read the paper. Larry cites a relevant portion at his blag, but the paper, quite clearly, states that there is a LOT of RNA in your cells that is just being transcribed by accident. Its just noise. Yet Casey made a conscious decision to disrespect these authors and the scientific community by misrepresenting their work to the general public: “DIRP! JUNK RNA CAN HAS FUNKSHUN! I PREDICTED DIS IN 1998!!! I ALSO INVENTEDED POGS!”
Of course, Casey is an IDiot. You cant really expect him to tie his own shoes, much less be literate. However, his IDiocy is once again your gain! Cause this paper is super cool, and I want to explain the details of what this group did for everyone 🙂
Guttman et al knew they had a lot of crap RNA to deal with, but they figured some of the transcripts might have a function we dont know about. So, they stacked the deck in their favor by using epigenetics! Yay!
No, not the happy hippy ‘birds singing is epigenetics, man’ epigenetics, I mean histone modifications that alter gene expression. Modify a histone one way, and the DNA wrapped around it snuggles up even tighter, preventing any transcription machinery from getting in. Modify that histone a different way, and it loosens up its grip on its DNA, letting the genes be transcribed. Guttmans group knew that if Histone 3 has a trimethyl on its lysine 4, then the genes around that histone are probably going to be transcribed.
So they used chromatin immunoprecipitation to purify all the histones with that specific trimethyl marker to find DNA thats being transcribed ‘on purpose’. They then whacked the DNA out of those histones hands and sequenced it. What DNA is associated with this kind of ‘active’ transcription? Well, once they eliminated all of the genes we know code for proteins and regulatory RNA, they were left with ~1,675 putative ‘JUNK DNA WIT FUNCSHUN OMG!’
Next, they took this DNA and created a microarray— When they dumped cell lyases on this array, if that cell made RNA that matches the chunks of DNA on the array, the DNA lights up and a computer can quantify it. 70% of their putative “JUNK DNA WIT FUNKSHUN! BLAAAAAK!” makes putative “JUNK RNA WIT FUNKSHUN! SHHNIG!”.
So they focused on figuring out what those RNAs were– they totally werent protein coding genes we just hadnt discovered yet, but they really looked like lincRNAs (large intervention non-coding RNA).
Most of the JUNK RNA weve found in other studies isnt conserved evolutionarily at all. Like, at all, implying there is no evolutionary pressure to keep this junk around cause its not functional. So to see if the remaining RNAs in their study might be functional, they compared their sequences (from mice) to 21 other mammals. While their RNAs werent as conserved as some proteins, RNA is slightly more forgiving than aminoacids, so they were happy with the level of conservation– these RNAs might have a function!
Using extraordinarily clever means, they figured out that some of their RNAs might play a role in ‘cell proliferation’ or ‘immune surveillance’ or ‘muscle development’, etc. When they screwed around with cells, they could alter the transcription of their maybe-functional-RNA, implying they might really be functional! WIN!!
In the end, they found 150 lincRNAs that are probably functional, and provided experimental support-of-functionality for 85.
This paper is really friggen clever, but to quote Larry:
Casey Luskin ain’t gonna disprove junk DNA using this paper.