Friday, July 1, 2011

If your genes are what you are, why don't you need them?

In a superficial way we can spoof the gene-for, genetic and evolutionary determinism that is so rife in and out of science these days.  If genes evolved by the eagle-eye of selection, fine-tuning your every move, then you should need your genes!

But study after study has begun to show that many or perhaps even most genes are not necessary. At least, they are not necessary in themselves.  The first kind of evidence that came to light more than 10 years ago was that transgenic gene-deletion ('knockout') mice could, about 30% of the time, live essentially normal lives without the gene that had been knocked out, often chosen because it had been identified as supposedly causing a human disease.  Then, in 2004 a paper in Nature reported the deletion of a huge section of a mouse chromosome -- it was a 'gene desert', no coding regions, but the region was large enough that it presumably included many regulatory sites, DNA stretches that control gene expression -- and found little if any difference, that is, no obvious impairment, in the mouse.  Similar results have been found in yeast and in bacteria (and probably other systems that we don't know about).

As human whole genome sequences began to become available, it was found that a person typically carries thousands of amino-acid changing variants.  If natural selection was such a fine-tuner, then we should not fare well with altered proteins.  Perhaps the sequenced individuals were normal because only one copy of the genes in questions was modified, while they retained a functional copy (though there were, as we recall, individuals with what normally were viewed as dominant modifications, where a single copy is enough to do the damage).  Perhaps one grudgingly could acknowledge that genes could be altered in ways that were not 'strong' enough to cause notably impaired function--of course, like biblical interpretation, such 'non-Darwnian' back-peddling opened all sorts of forbidden doors to the selectionist ideologue.

We can dismiss ideologues as benighted, despite their prevalence in and out of science.  After all, every one of us is probably ignorant in important areas.  But the dysfunction plot thickens:  We just learned of a recent study of 20 whole genome sequences in normal people that has found that an average person has about 165 doubly-killed (homozygous deleted) genes (some of these people were affected with a blood disorder that is known to typically involve a given gene, but this gene was not included in the figure cited here) (Pelak et al., PLoS Genetics, September 2010).  These genes were normally functional participants in different biological systems, and each of the 20 people had a different set. This implies that many more genes are dispensable in this sense, or dispensable in the environments or other genomic contexts of the individuals: the same gene might be lethal, even to the embryo, depending on its circumstances or the variants it carries at other gneies.

Nonetheless, these findings alone, unless there is a sequencing error problem, shows why genetic determinism, insufficiently tempered, is simply mis-understanding of biological causation.  The likely reason is that the pathways involved are redundant in various ways, with many ways to achieve the same trait.  Mapping (GWAS) studies have confirmed this idea par excellence.  So have experimental data, consistently.  And studies of humans and flies (as we recall) show that around 10% of variants that are seriously pathological in humans are normal in other species.

The results also show the problems with insufficiently tempered selectionism is simply bad evolutionary biology.  Natural selection, whatever it does, is typically not that fine a tuner.

Many if not most genes are, on their own, only partial determinants of an organism's traits, and this is  one reason why species can survive: otherwise mutations would have killed every individual off!  Whether redundancy evolved 'for' such a reason is debatable, but it is a fact of life as we see it today, after 4 billion years of survival challenges.

You and your genes are co-travelers in life.  But the relationships between you and your genes are subtle and to a great extent neither predicts the other.  Interestingly, each predicts the other very well in aggregate: what species you belong to, even what part of the world you or your ancestors come from.  But the kind of variation we talk about both in disease/GWAS, behavior, and evolutionary terms is less determinative.

Still, you and your genes certainly need each other overall.


Holly Dunsworth said...

I just logged on from Rusinga and read my first MT since being away...this is fantastic.

Anne Buchanan said...

We miss you, Holly! Hope the season's going well.