Introduction: The concept of a gene

If you ask 10 biologists to define the word “gene”, you will likely get slightly different answers from all of them. Some definitions might focus on the concept of a gene as the simplest unit of heredity, while others might focus on the physical properties of a gene as a segment of DNA.

The concept of a gene has changed throughout the history of genetics, beginning with scientists in the 1800’s. Early geneticists like Gregor Mendel, Thomas Hunt Morgan, and Barbara McClintock understood that there was a hereditary element that specified traits, although many of them did not use the word “gene” to describe this concept, and they did not know which biological molecule(s) might be the hereditary elements. Although Mendel did not use the word gene, his work on pea plants did give us the concept of a hereditary unit that specified a trait, as well as the concept of dominant and recessive alleles of a gene.

Mendel’s work did not receive much attention for until almost forty years after it was first published. But by the early 1900’s, additional researchers like Thomas Hunt Morgan and Barbara McClintock were exploring the concept of a gene. Thomas Hunt Morgan’s work in the fruit fly Drosophila melanogaster showed that the white-eyed trait was associated with sex, and he suggested that the trait might therefore be carried on the sex chromosomes that could be visualized microscopically. He further suggested that other traits might therefore be carried on other chromosomes. He later showed that certain genes were linked together in a linear fashion, with measurable distances separating linked genes.

Barbara McClintock’s work in maize (corn) further showed that distinctive traits were carried on physical chromosomes: she observed unique structural differences in the chromosomes of certain strains of maize, and she showed that the presence of these structurally unique chromosomes was associated with particular phenotypes.

In the early 1900’s, Archibald Garrod showed that hereditary traits were linked with biochemical activity. He was studying a hereditary illness called alkaptonuria, which causes dark urine starting as a newborn and a host of health problems later in life. He found that the disease is caused by a loss of function in the ability to metabolize the chemical alkapton. (We know now that alkapton is a breakdown product of the amino acids tyrosine and phenylalanine.) He later expanded his studies to include other inborn errors of metabolism, hereditary diseases that were caused by defects in enzymes important for metabolism. These studies showed a link between genes and enzymes.

By the 1940’s, George Beadle and Edward Tatum, studying amino acid biosynthesis in the slime mold Neurospora crassa, proposed the “One gene, one enzyme” hypothesis, which stated that each gene provided the instructions for one enzyme, and the function of the enzyme was what contributed to the phenotype of an organism. This was later revised to “one gene, one polypeptide” and when it was understood that not all proteins were enzymes and that many functional proteins were assembled from multiple polypeptide chains.

This understanding is reflected in the Central Dogma of molecular genetics, which states that information stored in DNA is used to transcribe (synthesize) RNA, that information in that RNA is used to synthesize protein, and that proteins (among them, enzymes) complete many of the biochemical and molecular functions of the cell.

Today, it is understood that even “one gene, one polypeptide” is an incomplete picture of what a gene can be. As we will see the section on RNA processing, one gene can often produce multiple distinct polypeptides. And many genes encode functional RNAs: RNA molecules that perform molecular functions themselves and are not used as a template for protein synthesis. A partial list of RNAs and their functions is listed in Table 1.

In this module, we will define genes as a segment of DNA that encodes an RNA molecule, although this too is considered an over simplification by many scientists^[1].

In this module, we will:

1. Compare the chemical nature of DNA and RNA.
2. Explore the DNA elements that surround a gene and provide information for the control of transcription in eukaryotes.
3. Compare and contrast this with the process of transcription in eukaryotes
4. Look at the ways eukaryotic mRNA are processed during and after transcription: polyadenylation, capping, and splicing.

In later modules, we will look at how some of these RNA molecules are eventually translated into protein and how gene expression is regulated.