Sunday 29 March 2015

Variation and lots of it

It's m'mother's birthday today!  95! Born in 1920 - not before the First War but as a consequence of it.  Her contribution to science has been immeasurable: just think that without her, there would be no Blob!  Turns out she shares a birthday with a much younger chap called Dick Lewontin (b. 29 Mar 1929) whose impact on my field, evolutionary biology, has been far greater than mine.  I'll give you one example today, it would tax your patience if I was to summarise all his contributions which include The Genetic Basis of Evolutionary Change which in its day (publ. 1974) was the definitive textbook.  In 1953, Crick and Watson worked out the structure of DNA, which could be recognised as the birth of molecular biology.  In 1966, however, two papers burst of the scene that made us question everything that we knew about the way evolution worked.  Lewontin and Jack Hubby published their findings on variation in the fruit-fly Drosophila pseudoobscura and Harry Harris published another paper showing very similar levels of variability in Homo sapiens.

What Lewontin and Hubby did was isolate proteins from a number of different flies, treat them in a scientific protocol of their own divising, load each sample into a little hole at the top of a slab of gel and apply a strong electric current [don't try this at home. kids] to sort them by their electric charge.  Some amino acids have positive charge, some negative and most are neutral. What they saw was really surprising: about a third of the proteins they investigated showed a pattern similar to that illustrated [L ripped from their original paper].  Each column represents an individual fly, some of which have 'fast' proteins, some 'slow' and some, called heterozygotes, have both varieties. What does it matter? 

It matters because the evolutionary gospel at the time was that Nature had been honed to a high level of perfection by millions of years of evolution.  Yes yes, of course there were exceptions, but almost all the exceptions were identified as "inborn errors of metabolism" such as phenylketonuria PKU, a disease which is tested for with the heel-prick test in all Western newborns.  We could accomodate such disease states in our worldview because, although they had effects that were bad for the propagation of the species, they were rare.  If 1:1200 babies are born with CF, and 1:10,000 have PKU, we are losing an insignificant fraction of the next generation.  But if a large proportion of the genes are 'deleterious' [bad!], the algebra suggests that we'd need to produce offspring like cod - which drop a million eggs at a sitting - to have a reasonable chance of having any humans (or fruitflies) in the next generation.  Suppose that 1:1000 children carry gene-variant X which means that they don't survive to have children of their own; that means that 0.999 of the population do survive to breed.  If the 'genetic load' in the population is two such duff genes, then only 0.999^2 of each generation = 0.998 survive.  But it is an exponential equation: 0.999^10 = 0.99;  0.999^100 = 0.90 (losing 1 in ten of all children born - before the ravages of infection, train-crashes and tsunamis have an impact); 0.999^1000 and 2/3 of the children don't make it.  Harris's data suggested that about 7,000 of our 23,000 genes are variable.

SO, the holy writ of then current evolutionary theory must be wrong!  Lewontin & Hubby and Harris forced us to re-appreciate our view of genetic variabilty.  There was a bitter rear-guard action by the 'selectionists' who held to the old view but by the end of the 1970s the 'neutralists' had won the war.  I was for years a naive pan-selectionist because my mind is so inert it takes a tock on the head with a bloody big hammer to change it.  But now I have joined everyone on the good ship neutralism and it shakes down well with my wider world-view.  There is a lot of variation out there; we are all different and we should celebrate it rather than labelling 'different' as 'worse'.

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