Wednesday, April 29, 2015
Human variation at every molecular level of control!
Its fun to sit back sometimes and reflect on the hubris of our species. Hippocrates first broke down all human body functions into these 4 humors, or temperaments.
Seems silly in hindsight, right? But this was the prevailing thought process for more than a thousand years. In my lifetime I feel like I've seen this occur as well. Probably the most fascinating was in how the lay public (and politicians...) really responded to the Human Genome Project. Alright...so now...we have a list of 16k or 18k (or whatever...) genes that can make proteins. EVERY time we really look at it we find more and more variation and levels upon levels of control. When I read things like this paper from Can Cenik et. al., it highlights 2 things. 1) How freaking awesome the tools we have right now are for all this stuff and 2) How little we know about anything. Honestly, sometimes I think we're closer right now to Hippocrates understanding of biology than we are to really really getting it.
Wow, I could use another coffee. Or more sleep. Sirens apparently make me rambly...sorry...what was I going on about? Oh yeah!
In this paper they take a look at a single cell type across a wide cohort of people. They use every tool in the current book (exaggeration...there are so many tools!); ribosome profiling, RNA sequencing and proteomics via mass spectrometry. What they found?!?! This mind blowing fact: individuals appear to control the regulation of what they express and when at an INDIVIDUAL level. What?
Consider it this way. If you wanted to understand how and why I made a certain protein and compared it to how and why you made that same exact protein you would find that the conditions might very well be different. Here is a (probably inaccurate) analogy I just made up on the fly: if you and I are sitting in a box in the desert and it was slowly getting hotter at some point we'd both start expressing heat shock proteins to protect our systems. We might upregulate them at different times due to an unbelievable level of variation between our two systems. Even if we did start producing these proteins at the same time, it might not be because of the same mechanisms!
Crazy cool, right?