Tuesday 22 September 2015

'Junk' DNA vs The World 2

Looking over the skyline of Camden as the sun sets on my first day of university life, I begin to to contemplate my place in our world. How much impact could I ever make? I am one average person in virtual sea of more prolific people, all trying to find meaning in an existence that intrinsically has none (I blame the Satorl Marsh night theme I'm listening to for that last bit). But my existential crisis aside, I did begin to think about the human genome, and how the neglected 'junk' elements of it must feel, always being in the shadow of the protein coding genes, which have a reputation as the be all and end all of molecular biology. Although personifying genetic material is not really a valid way to think about the issue... Therefore I will once again champion the Junk DNA in its quest for genomic appreciation. As I stated last time, human proteins are often the same size as equivalent proteins in simpler organisms; it is the sections of intervening junk that increase in size as the complexity of an organism increases. This creates what Nessa Carey describes as a large 'signal-to-noise ratio' during analysis of genes within our genome, as there's only a relatively small region that codes for protein, embedded in a large section of junk. But this DNA must have a role to play, otherwise we would be no more complex than a fly or a worm... (only a slight exaggeration...) Some complexity is added by post transcriptional modification of mRNA, in a process known as splicing. In splicing the exons, sections of DNA which code for proteins, are cut away from the intron sequences (the junk), and can be arranged in various fashions to generate different mRNA molecules from the same gene. Over 60% of human genes produce multiple splicing variants, however this only goes so far in explaining our relative complexity. Back in 2001, in the wake of the Human Genome Project, researchers thought the junk may not even have a functional role, as the pufferfish Fugu rubripes has a genome 13% the length of our own (devoid of much of the junk we see in our genomes), and is still a successful organism. It was hypothesised that the junk was parasitic, selfish DNA using our DNA as host for future proliferation (I just can't escape you Richard...). Although based on what we know about evolution, it is irrational to assume that just because the DNA has no obvious function in one organism, it does not mean it is useless in all organisms (especially in more complex species). One theory supporting the importance of junk DNA states that it could act as mutation insulation for the protein coding genes, as it makes it decreases the likelihood that a point mutation will affect a protein coding sequence, a benefit of the large 'signal-to-noise ratio'. The reason humans would need more mutation insulation than simpler organisms is because we have longer life spans, and therefore we accumulate more mutations, and we also produce fewer offspring, so it is beneficial that they are better protected from mutations in order to ensure species survival. In terms of cost-benefit, it isn't worth expending resources in simpler organisms to protect protein coding genes, as even if they accumulate a mutation they are still viable (fewer systems can be affected by the lack of protein production), and the offspring will likely still survive and breed (ah the virtues of simplicity). So who's irrelevant now 2001 geneticists? But seriously, if the junk DNA is used as a buffer for mutations, which have the potential to disrupt vital metabolic processes for example, is the nomenclature 'junk' still applicable? Not in my book, and this is my blog. Deal with it. How empirical of me.

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