Tuesday, July 30, 2013

You have no genotype, and you have no phenotype, either!

Yesterday we discussed the genomic heterogeneity that comprises each organism, except a single-celled organism during its pre-division lifetime.  When each cell divides into two 'daughter' cells, they both experience some mutations.  Since you are made of many billions of cells, and they are constantly turning over, you do not have a single genotype, and haven't had one since you started life as a single fertilized egg cell.

But, you might say, at least the result is a single phenotype, that is, you.  But that is not true, either.  The mutations in each cell are inherited in the cell's subsequent daughter cells during your life, and cells come and go, and the mutations may sometimes affect gene regions that affect their respective tissue, and hence the behavior of the tissue itself.  So, really, you don't have a specific phenotype, either.

One illustration of that is just the definition of different states.  Monday's NY Times reports a deliberation about 'cancer' and whether the definition or use of the term should change.  Many things, if not everything about you changes during your lifetime.  Cancer as we have called it is a disease resulting from some cells behaving differently from what is 'normal.'  Of course, that's happening all the time in your body, but the idea of cancer is that it is a lineage of abnormally dividing cells that grows without limits and thus threatens your life.  But not all abnormal growth is like that.

We've known this for decades or millennia.  Some growths are benign or haven't even been called cancer.  But even things that have been diagnosed as cancer are highly variable.  The new idea is that many that are slow-growing or not aggressive or not able to metastasize (spread to other parts of the body) are not dangerous and may never become dangerous.  They should not be called 'cancer', a scary word that is also expensive since doctors don't like to just leave it alone.  That's why it is perhaps wrong to screen too widely and diagnose something that will then have to be 'treated'.  But treatments all involve risk, if not also misery or fear, and expense.  So would re-defining be a good idea?

That's a clinical question we're not qualified to answer.  But we did think it relevant to the way we characterize people, and in particular, ways that could be dangerous to them.  We have in mind behavioral characterizations, especially when purportedly based on estimates of a person's genotype when s/he was a single cell, as estimated from a cheek swab or blood sample.  Not only do our cells' genotypes change with time, and due to environmental exposures, but our behavior is not nearly all hard-wired.  So really we don't have a clear-cut immutable phenotype, physically or behaviorally.

Of course, we are not completely changeable, so the challenge is to know what limits there are to change and how they are expressed or could be predicted.  The cancer story led us to raise this, as something to think about.  There is a tendency to simplify things beyond what is appropriate.


Anonymous said...

So the calculations on teleportation mentioned in this article http://phys.org/news/2013-07-infinity-teleporting-humans-space.html and based on the assumption that "one cell contains enough information to replicate any other type of cell in the body" are way off?

Holly Dunsworth said...

Whoever you are, you are a mind reader and I'm so happy for the link!!

Ken Weiss said...

Off by about the number of galaxies in the universe (100 billion). Teleporting one set of DNA (and, a cell, since DNA does nothing outside a cell (except degrade slowly) and that means the products of the mother's DNA, plus a cell's worth of mitochondrial DNA, will only get you a clone.

And that will not be a clone of the teleported astronaut-to-be, but of one of his/her somatic cells from a blood or cheek sample, which is different from what s/he started out as when a fertilized egg.

So what results will be a clone of the person's cheek! It will have some resemblance to the donor, sans the new somatic mutations happening upon arrival and embryogenesis in the spacecraft, and minus the donor's life-experience (and plus the clonee's life experience growing up in the spacecraft).

Yes, quite an adventure. As we've said before, this should be funded by Hollywood, not NASA. Hollywood has the money and they don't have to pretend to be doing science.