17 January 2017

Random Genome Facts

So, the human genome. Property of our species as a whole and each one his or her own individually. twenty-three pairs of macromolecules (chromosomes) made of smaller covalently attached molecules (nucleotides) in the nucleus of most of your cells; that, when unraveled (it is very well packed) is about three meters long. In an average human body there are almost 4 trillion cells, and a very conservative reasoning would be that around 3/4 of them have nuclei (and thus, DNA), so in your body you are carrying some twelve billion kilometers of DNA (among other things), which is enough to go to the sun and back. EIGHTY times.

Nucleotides, as I said, are the basic building block of DNA, or letters, and our genome is a three billion letters long book that tell our biological story at many levels (and you have around six trillion almost prefect copies of that in you). But books need structure, don't they? well, sort of. these letters make sentences (or genes, counting some 20,000 of those), which are (obviously) made of words and spaces (exons and introns). An average sentence (gene) has eight words (exons), and that makes your book around 160,000 words long (Tolkien's Silmarillion is 130,000 words strong for comparison).

You think those are not too many words? think of this. In an actual book, words are in an specific order forming sentences, paragraphs and chapters which would not make any sense of you scramble the order of the words. In the genome this happens all the time though, there are words (exons) that can be removed or added and modify the meaning of the sentence while making sense in the context of the story. Also, the sentences (genes) are not arranged linearly, but are scattered throughout the book, and you have to know in which order you can read them to make chapters (biological pathways) for the story to make sense. Plenty of those sentences (genes) can be found in different chapters, making perfect sense as they are in two or more places, or maybe just removing or adding a word. FYI, each variation of a sentence (gene) caused by the removal or addition of one word (exon) is called isoform (no equivalency here with literature, that I know of).

So we all have all these three billion nucleotides (or letters) in our genome, then what makes each of us a special snowflake? Genetic variation, as a very simplified explanation, the letter in each of those position (and there are four possible letters: A, T, C and G) can change for different reasons, and that is called a mutation. even though all of the three billion letters can change, only some of them (80 million) have been described to actually change in human beings.

And this takes us to the last curiosity about the genome, or how many different possible people there can be due to genetic variability (or in other words, due to the specific set of mutations that we carry in our genomes; and, yes, we are all mutants, no matter what the x-men comics would have us believe, the thing is each of us are mutants for a different set of changes, which is unique to us). Some big numbers first: there are 10 to the 120 (or 10,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000000,000,000,000,000,000,000,000,000,000000,000,000,000,000,000,000,000,000,000) possible ways in which a chess match can go down; there are 7.5 multiplied by ten to the 18 grains of sand on planet earth  (or 7,500,000,000,000,000,000); there are 100 billion galaxies and 300 billion stars on average on each one of those (not that much of a deal) and around 10 to the 90 atoms in the universe.

Prepare for this.

The combinatory of 80,000,000 (the total number of potential letters that can change, mutate, in our genome) is 2 to the 80,000,000, which is far FAR greater than 10 to the 1,000 (remember there are 10 to the 90 atoms in the universe). 2 to the 80,000,000 possible humans thanks to our genetic code. And that is not taking into account other sources of variation, like CNVs (copy number variation) or structural variation (like the loss of a whole part of a chromosome of the very famous trisomy  of chromosome 21). Think of how unique you are.

Or as Richard Dawkins puts it:

“We are going to die, and that makes us the lucky ones. Most people are never going to die because they are never going to be born. The potential people who could have been here in my place but who will in fact never see the light of day outnumber the sand grains of Arabia. Certainly those unborn ghosts include greater poets than Keats, scientists greater than Newton. We know this because the set of possible people allowed by our DNA so massively exceeds the set of actual people. In the teeth of these stupefying odds it is you and I, in our ordinariness, that are here.We privileged few, who won the lottery of birth against all odds, how dare we whine at our inevitable return to that prior state from which the vast majority have never stirred?”

Have a nice day snowflake.