You are your mother's mother's mother.

After a halting start, this blog seems to have fallen by the wayside.  So my resolution for 2011 is to do one paper a week.  We'll see how that goes, but in the meantime let's talk about a little round piece of extranuclear genetic material in all of our cells: mitochondrial DNA, or mtDNA.

The mitochondria are the little energy factories within our cells, taking sugar (well, sugar derivitaves really) mixing in oxygen, and making lots of ATP, carbon dioxide, and water.  It's hypothesized they started as a symbiotic bacteria in an ancestor cell looooong ago which got cozy and took up permanent residence.  The mitochondria precursor had it's own circular DNA which liked its new home so much, it  kicked out lots of the genes it no longer needed.  Nature is lazy, so duplicate genes in the chromosomes were deleted from the mtDNA.  Mitochondrial DNA contains some genes essential for making copies of itself (replication), and for a few things that only happen in the mitochondria, just 37 in total.  It's a lean, mean replicatin' machine.

There's lots about mtDNA we can talk about, but let's focus on inheritance.  You inherited 99.999999999% of  your mtDNA from your mother.  And she inherited hers from her mother.  And so on. So much so, a really neat book on the subject was written that traces all of humanity back to seven women, based on mtDNA studies.  Why do we all carry our mother's mtDNA?  When you were just two halves of a cell, the big pillowy egg cell from your mom carried all the good gooey innards whereas the teeny sperm cell from your dad only carried tightly packaged chromosomal DNA - no room for mitochondria, no room for mtDNA.

A big question is why trace lineages from mtDNA?  It could also be done through X or Y chromosomes.   However, the Y chromosome is not a good candidate because, first, only half the population will have a Y chromosome.  Second, the Y chromosome is highly palindromic, meaning lots of the sequence mirrors itself.  Thus, it's a technical challenge to be able to accurately sequence most regions. Perhaps this warrants further exploration another day. The X chromosome would be a great candidate, but it's big.  Much, much bigger than most chromosomes.  Containing about 1098 genes and containing 150,396,262 base pairs (give or take), the X-chromosome is quite a beast.  Getting all researchers to agree to track subtle changes in small regions of such a large hunk of genetic material would be fraught with lots of ego battles, for sure. Not that there's any ego in any of this, right?

So, why mtDNA to trace lineages?  The answer is that humans, like nature, are pretty lazy too.  MtDNA is pretty small - only 16,500 base paris.  And there are just a few regions that can be mutated with no consequence to the genes.  Since these areas mutate at a predictable frequency, about 1 in every 33 generations, (much higher than in chromosomal DNA) these regions can serve as pretty neat molecular clocks.  The mutations give clues to how long it's been since these mutations arose, and when one person's mtDNA is compared another's, or to ancestors, researchers can make guesses as to who is related to who.

Neat?  You bet.  Practical?  Of course.  Stay tuned!

Term Tuesday: Proteasome

Today's term is Proteasome.  Never heard of it?  Cool.  Let's get started then.

 Like every good city, someone needs to take out the trash and the proteasome is the one to do it for a cell. The proteasome is the trash compactor and recycling center for proteins in a cell. The proteasome is a big, barrel shaped protein complex in a cell (we're talking eukaryotes here) that degrades and disassembles bad proteins.  By bad proteins, I mean proteins that were made or folded improperly, proteins that no longer are needed, and proteins that have been damaged, say by heat shock.

The proteasome is made up of several protein complexes that arrange themselves, I kid you not, like a kitchen trash can with a pop-up lid.  The details get my head spinning, so I'll probably not do justice to the amazing research behind discovering how it works.  But here it goes.  The main barrel of the proteasome trash can, called the 20S particle, is made of small proteins aggregating together to make rings. There's 7 rings in the barrel, and the outer two contain regulatory elements that can sense what proteins are entering to be degraded. The lid of the trash can, called the 19S regulatory cap, senses the proteins to be degraded and feeds them into the barrel.  It takes energy to destroy a protein and the energy comes in the form of using ATP, the main fuel in the cell.  The energy spent here is in the binding of the bad protein to the 19S and 20S particle.  There's yet another part of the trash can, the 11S particle, and it regulates degradation of short proteins or peptides.

Proteins are generally tagged for destruction by a small chemical modification called ubiquitin.  Attaching onto the amino acid Lysine, the ubiquitin is placed on there by yet another complex of proteins called ubiquitin ligase.  The ubiquitin ligase is the trash collector: it identifies the proteins in the cell that need to be recycled.  You guessed it, there's several proteins associated with ubiquitin ligase, and it's where the specificity comes into play. When a protein is tagged for destruction, it attaches to the 19S (or 11S if it's small) particle and is fed into the 20S particle.  It's here that it gets chewed into small peptide chains, which can be further degraded and recycled into new proteins.  Nice and tidy.

Proteasomal degradation of proteins plays a huge role in the normal control of cell division, homeostasis, and stress response.  However, sometimes the proteasome degradation process goes awry, and can lead to disease.  Too much proteasomal activity can lead, supposedly, to autoimmune disease.  Not enough can lead to things like Alzheimer's disease and cancer.

Remembering back to high school biology (quite a few years back, I won't tell you how many) I never learned about proteasomes. It's because they probably weren't identified yet as parts of the cell. They were only really discovered in the '80's.  And work that identified it was deemed worthy of the Nobel Prize in 2004.  Really, we all should celebrate those who know how to take out the trash.

P.S.  I'll get to actually putting in reference and attributions here soon.  I promise.

Term Tuesday: SNP

Wow.  This little blog has 2 followers.  That's more followers than there are posts.  Crazy.  OK, well, not to disappoint my fans, I will renew my effort to explore the world of biological science, particularly genetics with you.

So... introducing Term Tuesday, where I'll pick some cool term at random and try to shed light on what it means.

Today's term is SNP.  Most people pronounce it "snip".  It stands for  Single Nucleotide Polymorphism.  Kind of a mouthful, no?  Maybe, but it's pretty simple. While most of our genes are made up of the same combination of the nucleotides A, G, C, and T, from time to time there will be one "letter" different.  A single nucleotide. And this small difference is not enough to change the resulting protein product, or whatever that piece of DNA encodes.  It's just enough to be a variation, or polymorphism. Like a different way of spelling the same word.

So why do people care about SNPs?  Turns out they can be very useful.  One example of how they are cool is that SNPs can be used to identify candidate disease genes.  Since everyone carries around a different combination of SNPs, geneticists can compare SNPs in people with a disorder to people without a disorder.  If enough SNPs associate with a disease, there's a good chance a gene associated with the disease is located on the DNA near the SNP.  So SNPs can act as a road mile marker.  They're so useful in fact that researchers have identified common SNPs in the population and put them all on a gene chip, to make the identification process go that much faster.  Once a set of SNPs have been identified, a small chip containing disease-related SNPs can be made, to quickly and economically assess someone's risk for carrying a yet-to-be-identified disease gene or genes.  Neat, huh?

I bet there's lots more about SNPs but that's all I have time for today.   Any driving questions?  Just post a comment!