Just What Is A Gene, Anyway?

The science of genetics really got its start in the year 1900, with the rediscovery of Mendel's work by three different groups of scientists, in three different parts of the world.

For a number of years, the new discipline thrived on delving into the mysteries of the transmission of traits from generation to generation, reaffirming Mendel and elaborating beyond the basic principles he'd discovered.

But eventually attention began to focus on a different question. Just what is a gene, anyway? What is it made of, and how does it do what it does?

This was a question for the biochemists. And they had a good start on the answer already, because the Mendelian geneticists had already answered the question of where genes were in the cell. They were in the nucleus. More specifically, they were in the chromosomes, a fact that was established before the end of the first decade of the century.

So genes were in chromosomes. And everyone knew what chromosomes were made of. They were about 50% histones (a class of protein) and 50% deoxyribonucleic acid (DNA). So if genes were in chromosomes, then they must either be made of protein or of DNA. But which?

By the 1930's, quite a lot was known about proteins. But DNA was largely unstudied and considered to be a pretty uninteresting substance. Nobody knew how it was put together, and it didn't really show up anywhere else, doing anything else, in the cell. By contrast, proteins were everywhere, doing all kinds of things. In fact, it was pretty clear by this time that the job of a gene was to tell the cell how to make a specific protein.

And that was the next key. Whatever genes were made of, it had to be a substance that could carry information--that's what "instructions" are, information. So the question became, "Which of these molecules is a better candidate for an information-bearing molecule?"

It may surprise you to discover that the smart money was on protein, not DNA, as the answer. Here's why...

First, remember what you've already learned about protein. There are thousands of different kinds of proteins in every cell, carrying out pretty much all of the important functions that go on in cells. In other words, it was already known that proteins do about everything that gets done in cells. What did they know about what DNA does? Well, nothing. DNA had never been implicated in any function in the cell.

But more significantly, it just didn't seem possible that DNA could carry so much information--enough to provide instructions for making all the billions of different proteins found in all the creatures of the world. This is the information-storage issue. Those biochemists knew that whatever genes were made of had to be capable of carrying a lot of information. This implies that the molecule must have a lot of internal complexity.

Both protein and DNA are made out of long chains of smaller molecules. Proteins are constructed out of a set of twenty different amino acids. A typical protein contains perhaps 150 amino acids, selected from that "library" of twenty amino acids, and strung together in a specific order. The biochemists of the later part of the first half of the twentieth century knew this. Protein... twenty different amino acids.

DNA is made out of smaller molecules called nucleotides. Like the amino acids in proteins, these nucleotides are strung together in long chains, though this was something that was not yet known about DNA structure at the time this puzzle was under consideration. But here's the catch... Where proteins are made from a selection of twenty different amino acids, DNA is made from only four different nucleotides.

What obvious conclusion should one make? Twenty interchangeable parts vs. four interchangeable parts, in a molecule that you know must provide a great deal of complexity. Of course the smart bet was on protein as being the substance out of which genes were made.

However, the smart money isn't always bet on the eventual winner of the race ;^) A series of extremely clever experiments in the 1940's demonstrated without possibility of doubt that the part of a chromosome that carries genetic information is not protein, it's DNA. Surprise!

This discovery set off a flurry of interest in DNA. Laboratories all over the world forged ahead in the study of the structure of this molecule that everyone had considered to be essentially unimportant. A sort of unofficial race among scientists around the world was eventually won by a pair of dark horses in England, James Watson and Frances Crick. Their discovery of the structure of DNA, published in 1953, set off an explosion in an entirely new kind of genetics: molecular genetics.

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Updated 25 September 2004