Friday, January 31, 2014

Defining the Genome

Here’s another one! A big essay on central dogma is coming up, so again there’s that problem of getting some background work done before I start putting up the really complicated stuff. It’s like watching Doctor Who from the middle, you know? Sometimes you’ve just gotta start at the beginning or nothing makes sense.


Defining the Genome

As most already know, at the very heart of any genome is something called DNA, or deoxyribonucleic acid. DNA consists of two strands twisted into a double helix, (the sugar-phosphate backbones) with “ladder rungs” connecting in the middle. These “ladder rungs” are actually called nitrogenous bases, and they are the smallest units of the structure.
                There are four nitrogenous bases; adenine, thymine, cytosine and guanine. Most geneticists shorten these to A, T, C and G. To save things from getting too complicated, DNA is read from only one strand at a time; this is what is meant by a DNA sequence. DNA is double-stranded so that each base can form a chemical pair with the base across from it. These unions are called “basepairs”, and they are at the heart of DNA’s function. But, certain bases can’t pair with each other; the pairs are limited to A/T or vice versa, and C/G or vice versa. And it is the different combinations of these bases that makes your DNA, and by extension you, unique. And together, they form deoxyribonucleic acid.
                DNA is an incredibly complicated thing. The amount of basepairs in a single human genome alone amounts to roughly 3 billion. Early estimates to the size of the human genome were done by measuring the amount of genes in a cell. This gave us a pretty good idea of how things worked on that level, but the idea to go about sequencing the entire genome from start to finish didn’t come up until the mid-80’s, when capillary sequencing was developed. When it first got started in the 1990’s, the first five years were devoted to just mapping the chromosomes. Chromosomes display banding patterns when treated with a chemical agent. These parents are very unique, and can be used to identify individual chromosomes.
                Within each chromosome are certain regions. That way you can find out which genes are located in each region. All of this “physical mapping” was done before the sequencing even started.
                When mapping with chromosomes, they wouldn’t pick a single chromosome and build up from there. No, they would pick many and go out. That way, they could easily see how the different chromosomes interconnected.
                Of course, the project eventually succeeded. And we now know much, much more about the human genome, and even genomes in general, than ever before. For instance, it’s been discovered that the amount of basepairs in a genome doesn't actually do much to contribute to the complexity of a species. In fact, sheer size is insignificant compared to the specific sequence. It’s how the bases pair, not how many pairs there are, that makes the difference. Salamanders, for instance, have many more basepairs than humans. And in fact, large genomes can sometimes mean problems; genomes often get big because viruses sneak their way in and replicate. This is one cause of repetitive regions, regions in a genome where the same sequence repeats over and over. These are the remnants of dead viruses which still function to some extent, and can jump around and insert themselves elsewhere in the genome, causing problems.
                Now, here’s the fun part; every human being has two copies of the genome in each of the trillions of cells in our body, each cell reading a different part of the “instructions”. Each copy, if you were to stretch it out to its full length, would measure out to almost two meters. That’s pretty impressive. The problem? Each set of genomes has to fit neatly into a chromosome – where the DNA lives – which is considerably smaller than DNA is long. So how does it all fit? The answer is in histones. Histones are highly alkaline proteins found which help package and order the DNA into structural units called nucleosomes. Think of it as a strand of yard wrapping itself over and over around one post, then stretching to the next. Then wrapping itself over and over around that post, and proceeding to the next. And so on and so forth. This storage method works so well that all 3 billion basepairs – a copy of each set, one from mom and one from dad – fits into a single chromosome.
                The chromosomes, when ordered, occur in pairs. In humans, each cell contains 23 pairs of chromosomes, for a total of forty-six. Some are duplicated chromosomes (the ones that look like X’s) and some are non-duplicated (the ones that look like I’s) but this doesn’t make much of a difference. Except in the last pair, which are a bit different; in each cell there are 22 pairs of autosomes, and one pair of sex cells; these are the famous X and Y chromosomes that determine whether an individual has male or female biology. Every female in the human species has two X chromosomes, and every male has one X and one Y. The reason males can’t have a matching pair is because without the X chromosome, a human being would die. The X chromosome is ultimately more complex than the Y, and vital to human survival.
                And so, all in all, there are 23 pairs of chromosomes in each cell, including 44 autosomes and two sex cells. But there’s also another set of DNA, that lives outside the cytoplasm cell, inside another organelle (an organelle is basically an organ for a cell.) This brings us to the mitochondria, a vital part of cell biology, which has its very own set of DNA.
                A mitochondrion produces boatloads of energy in the form of the molecule ATP, or Adenosine Triphosphate. A cell can actually have many mitochondria at a time, ranging in number from a few to several thousand. They are passed down only through the maternal line, and, (trivia time!) used to be their own free-living bacteria.
                Scientists theorize that mitochondria were a separate entity long ago, but were devoured by some ancestral cell and integrated into our biology. Now it works for us, despite having its very own set of DNA. Mitochondrial DNA exists in the form of a chromosome just like nuclear chromosomes. (Nuclear being chromosomes that reside within the nucleus of a cell, rather than separately in a mitochondrion.) But the mitochondrial chromosomes aren’t linear; they’re circular. And each chromosome has only 17,000 basepairs. Does your head hurt yet? Mine did. And we’re just getting started…

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