As Promised: Genetic Mapping

Fig. 1. T. H. Morgan's lasting scientific influence is evidenced by the large number of geneticists who name their cats after him.

RPM pointed out in comments to my post on "decoding" that another frequently misused term is 'mapping'. It doesn't bug me quite as much, because physical mapping can at least be a step in the genome sequencing process. However, like 'decoding', there's some fascinating science and history behind genetic maps that gets ignored in the confusion. So, in the naive belief that at least three of my readers aren't already biologists, here's What A Genetic Map Is And Why It Is Neither A Genetic Code Nor A Genome Sequence.

Genetic mapping was discovered way back when the science of genetics was very new. Watson and Crick determined the structure of DNA in 1953, and Hershey and Chase proved that DNA was the stuff of heredity only a year or so before that, but the first genetic map dates from 1911. A 19-year-old called Alfred Sturtevant drew it in a single evening, "to the neglect," he said, "of my undergraduate homework."

As is always a good idea, Sturtevant had made a wise choice of advisor. Thomas Hunt Morgan ran the new Drosophila laboratory - the Fly Room - at Columbia University and was working on the phenomenon of linkage, which he rightly considered to be good evidence for the Chromosome Theory of Inheritance.

At this point a 'gene' was merely a hypothetical entity, a symbol, that corresponded to a difference between individuals. There was debate for decades afterwards about whether genes even existed in any physical sense. The chromosome theory bypassed that question, holding that whatever-the-heck they consisted of, genes were nevertheless in, on, associated with, or stuck to particular coloured blobs that were visible in cells under certain staining conditions - chromosomes, which roughly translates as coloured blobs. (I love how the bewilderment and uncertainty of a dawning science shows in the jargon.)

Linkage is perhaps best described as "what Mendel missed". Everybody's favourite kitchen gardening monk-mathematician had shown in 1865 that when genes passed from generation to generation, they did so independently of one another: for example, inheriting your father's dark hair makes it no more and no less likely that you will inherit his blood type. This became known as Mendel's Second Law, or the Law of Independent Assortment, but exceptions were found almost as soon as anyone started looking for them. Sometimes, it seemed, a pair of characteristics tended to be inherited together.
For example, if you crossed a sweet pea with long pollen and purple flowers to another sweet pea with round pollen and pink flowers, the seedlings rarely had long pollen and pink flowers (or round pollen and purple flowers). They usually resembled one parent in both characteristics.

Morgan reckoned that if the genes were on the chromosomes - and there were certainly more genes than chromosomes - then these exceptions to Mendel's Second Law could be caused by pairs of genes close together on the same chromosome: that is, genes that were linked. So scientists in the Fly Room were busy finding as many examples as they could of differences between flies that could be conveniently used in crossing experiments: white versus red eyes, rudimentary versus normal wings, and so on - and looking for pairs of linked genes. Sometimes genes were tightly linked, meaning that almost no offspring were ever found with a combination of both parents' characteristics, but sometimes there was a sizeable minority of these "recombinants".

Sturtevant took the idea one stage further. If the loosely linked genes were far apart, and the tightly linked ones were close together, it should be possible to sketch out the relative positions of a whole group of genes, and then use that sketch to predict what the offspring of new experimental crosses should look like and how many recombinants there should be of each type.
It worked. All the genes could be plotted on one straight line.
Over the following years, more genes were discovered and added to the map. It kept working, and it worked for other species too. For any particular species there always turned out to be as many groups of linked genes on the map as there were chromosomes in the cells.
Eventually, this forced the opponents of the chromosome theory to shut up.
And they all lived happily ever after.
And the moral of the story is Never Do Your Homework.

Phoebe Sturtevant and Lilian Morgan also worked hard in the Fly Room, but got little credit for their contributions. When TH Morgan first visited Lilian after she gave birth to their eldest child, she asked after his new white-eyed mutant fly before he had a chance to ask after the baby. I've heard this story quoted as an example of what a dedicated and obsessive scientist he was, weirdly enough.
However, Phoebe is quoted as saying that Drosophila geneticists make good husbands, so I was very happy when my best friend married one.