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3rd-Jul-2009 01:30 pm - Alternative Splicing
fry
So, for everyone here who hasn't studied molecular biology,
The flowchart in the human body from DNA to protein goes like this: DNA -> pre-mRNA -> mRNA -> polypeptide sequence (protein).

It is strangely similar to a computer system. The DNA is similar to the 0s and 1s of binary of data (except it is base 4), the pre-mRNA is a chunk of data from the DNA which is sent off to processing into mRNA. The mRNA is then translated into proteins via codons in the sequences (sequence of three DNA monomers representing one amino acid, think of an 8-bit character from ASCII). Proteins are the physical workhorses of the cell and are similar to compiled objects in an object oriented language. The big difference is that there's no human programming language for gene or protein construction; evolution works stochastically so it's not necessary.

Anyway. What I'd like to talk about briefly is the process of turning pre-mRNA into mRNA. pre-mRNA contains sequences of exons and introns. Exons contain expressed series of information, while introns are generally excluded from being translated into a protein by being cut out of the pre-mRNA by intracellular machines known as spliceosomes. Think of it like a Mad magazine cutout. To get the punchline, you have to fold over a big chunk of the image. That's what your cells do to pre-mRNA when they splice it to become mRNA which is translated by ribosomes into protein.

Cells are smart creatures thanks to millions of years of evolution and use this to their advantage. Let's say a piece of pre-mRNA has a sequence 1EEEEE 2IIIII 3EEEEE 4IIIII 5EEEEE 6IIIII 7EEE, where I represents introns and E represents exons. It was orginally thought that this sequence would only yield one protein, in which the exons would be joined after the removal of introns to give 1EEEEE 3EEEEE 5EEEEE 7EEE. But that's not what usually happens. Instead, the multiple series of sequences actually can be processed in other ways to yield different mRNA, like only appending either 5EEEE or 7EEE at the end. This gives two different proteins in a form of data compression very similar to file compression algorithms like zip. Large multicellular organisms take great advantage of this: the gene Dscam from fruit flies, critical for brain development, can code for over 38,000 different proteins (termed isoforms). Occasionally, even introns can be become translated (especially in the case of cancer cells). This is why the human genome, when compared to microscopic organisms like Amoeba Dubia, may seem very small. In actuality, it is very highly compressed and refined.

This intelligent splicing is all regulated by the trans- and cis-acting elements. Trans-acting elements are external factors such as binding proteins which cause a piece of pre-mRNA to be preferentially spliced or avoided (activation or repression), while cis-acting elements are sequences of ribonucleic acid inside the piece of pre-mRNA which promote or diminish splicing (enhancers or silencers). For instance, by binding to a trans-acting binding protein, a given sequence of pre-mRNA behaves in a cis-acting fashion. At a detailed level the regulation of pre-mRNA splicing becomes fairly complex and there is still a large body of research that needs to be conducted before a precise understanding is established.

So, why's this all important? It's believed that 15-50% of human genetic disease is resultant from errors in splicing. For instance, a single amino acid mutation in the intron for the gene of TPH1 (tryptophan hydroxylase type-I) is highly correlated to the development of schizophrenia. While not being a part of the actual translated protein, it may serve as part of a cis-acting strand in the pre-mRNA that regulates the splicing of the gene. Incorrect splicing is also strongly implemented in the development of cancer.

Further reading: Understanding alternative splicing: towards a cellular code
27th-Apr-2009 11:58 am - Important post
pills
18th-Mar-2009 01:15 pm - Just When You Thought It Was Simple
pills
It's a mistake to assume you were born with such and such genetic material and that you'll always manifest as the same human being if they were to clone you today.

Transposons are sequences of DNA that are able to hop around through an organism's genome mostly in a cut and paste like fashion. They quite good at causing mutations (and therefore inactivating genes). They make up 44% of our genome and about 0.022% of the active genetic material in the human body. That may not seem like a lot, but keep in mind the human genome is slightly over 3 billion base pairs and we have only been able to find uses for 1.5% of it so far. This would partially explain why our genomes vary with age.

The nucleus of the cell also offers an interesting center for progressive genetic manipulation. Much of human genetic code is shuffled off into the storeroom like heterochromatin, while a much smaller amount is actually actively involved in the production of RNA in the euchromatin. The genes can move back and forth between these, causing previously inactive genetic material to be translated and vice versa. Research has shown that doing damn near anything to a cell changes its genetic expression in the nucleus.

Between all this it's surprising we don't wake up a different person everyday. It probably explains some of the seemingly idiopathic developments of genetics-related diseases late in life, too (aside from all the usual carcinogens we're exposed to on a regular basis).
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"EDMONTON — An academic maverick is challenging conventional wisdom on Canada's prehistory by claiming an archeological site in southern Alberta is really a vast, open-air sun temple with a precise 5,000-year-old calendar predating England's Stonehenge and Egypt's pyramids.

Mainstream archeologists consider the rock-encircled cairn to be just another medicine wheel left behind by early aboriginals. But a new book by retired University of Alberta professor Gordon Freeman says it is in fact the centre of a 26-square-kilometre stone “lacework” that marks the changing seasons and the phases of the moon with greater accuracy than our current calendar."

In other news I've been losing my mind.
8th-Jan-2009 03:57 pm - Mission: Yumpossible
pills
I just solved this integration problem (area bounded by y=3-x^2, y=1-x, x=-2, x=2) over the course of an hour and a half and the solution came out to exactly four units squared. Whoa.

Then I went to use the rest room, came back, and spent 20 minutes trying to figure out how to operate the keypad device to enter the room. As it turns out, you have to enter the digits really slow after you use your keycard or it doesn't work.

Shit was intense, yo.
7th-Jan-2009 12:39 pm - Computer Nerd Moment
pills
Why the Core i7 sucks and the Phenom II may actually give AMD the advantage again:
•Core i7 only supports DDR3 which remains more than double the price of equivalently fast 1066mhz DDR2, while the phenom II supports both
•QPI will be about half the speed of the new generation of AMD hypertransports 3.0 and 3.1 (25GB/s vs 50-60GB/s)
•Phenom II will remain cheaper than the Core i7
•Both will have similar cache sizes with similar overclockability (with the phenom II probably leaning towards the winner as far as the latter)
•I am a nerd
6th-Jan-2009 07:08 pm - Gay
jackovaggio
Yesterday I had my first calc II class. The teacher stated that it would be one of the hardest courses I would take in university and that I must know everything learned in calc I by heart. Lucky for me I took calc I five years ago and remember shit all about it.

Ballsasstwat. I'm going to give it three weeks and if I feel like it's giving me a thrashing I'll drop it and try to get it done in the summer or later.
13th-Dec-2008 06:03 pm - Cram
arnold
Androdioecy is a reproductive system found in species composed of a male population and a distinct hermaphrodite population. Such species are rare.
10th-Nov-2008 09:54 pm - Fisto
arnold
I've been playing Fallout 3 more.
I found an item called "Fisto" in a powerplant in the way northeast corner. It's a mechanical fist that makes heads explode and bodies fly when you punch things. I uppercutted a supermutant into the ceiling of a church and his head got stuck in the rafters and he just kind of dangled there.

...This is the most fun I've had playing a video game in a long time.

I should quit procrastinating on this chem lab report...

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