Friday, December 14, 2012

Ask A Scientist: How Does Joint Flexibility Work? (1)

Spaceman Spiff asks: "I've always wondered about what makes bodies flexible. I get that practice and maintenance make one flexible, but what biologically makes the difference between, as an example, being able to do a split and not being able to do a split?"

Here is a really short answer: Some of it is practice.  Some of it is genetics; it is generally accepted that tendons and ligaments are less important to flexibility than the muscle sheath.  There is a large collection of genetic diseases that cause hypermobility (abnormal flexibility), so I discuss genetics below. In part 2, I'll discuss what's known about the hypermobility syndromes, because they provide a good window into how flexibility normally works.

Below is a brief summary of how (some) human genetics work.  If you are a geneticist, feel free to  look away and come back another day. (It's actually a lot more complicated than this. I KNOW.)

Genetically-normal people have 46 chromosomes.  Chromosomes are full of little chunks of genes called open reading frames, where DNA is turned into RNA (transcription) and then, sometimes, into proteins (translation).  There are also many kinds of regulatory regions, that control when and how genes are transcribed, how much of the gene product (RNA) is produced, and so on.  RNA itself is translationally regulated - so there are several layers of control.  The regulation generally happens via proteins - the proteins bind the DNA or RNA, and sometimes other pieces of DNA or RNA.  Some RNA is cut up into tiny pieces called microRNAs (miRNA) which can also bind a really complicated apparatus that provides another level of regulation. (Does your head hurt yet?)

Short version: Lots of different things affect how protein is or is not produced from any given gene, when, and under what circumstances.  Imagine a set of 10, or 100, giant spiderwebs, all connected to each other.  That's the regulation of an average gene. 

Gene mutations happen all the time.  There is a range of normal.  Sometimes it's hard to figure out if something is a normal variant or an out-of-normal mutation. On the one side, you have people with bright green eyes: unusual, but normal, and more to the point, not harmful.  On the other side, you have a point mutation in CFTR that leads to cystic fibrosis.  In between is a whole range of maybes and sometimes.

Genes that require only one copy to produce the relevant trait are called dominant; otherwise, they are recessive.*  However!  Due to the regulation I talked about above, two people with the same exact disease-causing mutation will not necessarily have the exact same symptoms, progression, or prognosis.  So one person in a disease-affected family may die very young, and that person's child or parent may live to be sixty. (Here is an example.  If you are interested, search 'familial incomplete penetrance' on PubMed.)  There are also diseases with very high penetrance and expressivity: familial early-onset Huntington's is one.  

Next time: What Do Genetics Have To Do With Stretching???

*Except for pseudodominant genes, which happen largely through the sex chromosomes.

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