Unit Three. The Continuity of Life


12. How Genes Work



Ribosomes, like the one you see here, are very complex cellular machines that assemble the polypeptide segments of proteins, using information that has been copied from genes onto RNA molecules. The ribosomes read the gene information copied onto these messenger RNA transcripts, and use it to determine the amino acid sequence of the new polypeptide that the ribosome is assembling.

Each ribosome is made of over 50 different proteins (shown here in gold), as well as three chains of RNA composed of some 3,000 nucleotides (shown here in gray). It has been traditionally assumed that the proteins in a ribosome act as enzymes to catalyze the amino acid assembly process, with the RNA acting as a scaffold to position the proteins. In the year 2000 we learned the reverse to be true. Powerful X-ray diffraction studies revealed the complete detailed structure of a ribosome at atomic resolution. Unexpectedly, the many proteins of a ribosome are scattered over its surface like decorations on a Christmas tree. The role of these proteins seems to be to stabilize the many bends and twists of the RNA chains, the proteins acting like spot-welds between the RNA strands they touch. Importantly, there are no proteins on the inside of the ribosome where the chemistry of protein synthesis takes place—just twists of RNA. Thus, it is the ribosome’s RNA, not its proteins, that catalyzes the joining together of amino acids! Clearly, our knowledge of how genes work is still increasing, often adjusting what seem to be fundamental concepts.


12.1. The Central Dogma


The discovery that genes are made of DNA, discussed in chapter 11, left unanswered the question of how the information in DNA is used. How does a string of nucleotides in a spiral molecule determine if you have red hair? We now know that the information in DNA is arrayed in little blocks, like entries in a dictionary, and each block is a gene that specifies the sequence of amino acids for a polypeptide. These polypeptides form the proteins that determine what a particular cell will be like.

All organisms, from the simplest bacteria to ourselves, use the same basic mechanism of reading and expressing genes, so fundamental to life as we know it that it is often referred to as the “Central Dogma”: Information passes from the genes (DNA) to an RNA copy of the gene, and the RNA copy directs the sequential assembly of a chain of amino acids. Said briefly, DNA → RNA → protein.



A cell uses four kinds of RNA in the synthesis of proteins: messenger RNA (mRNA), silencing RNA (siRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). These types of RNA are described in more detail later in this chapter.

The use of information in DNA to direct the production of particular proteins is called gene expression. Gene expression occurs in two stages: In the first stage, transcription, mRNA molecules are synthesized from genes within the DNA; in the second stage, translation, the mRNA is used to direct the production of polypeptides, the components of proteins.


Transcription: An Overview

The first step of the Central Dogma is the transfer of information from DNA to RNA, which occurs when an mRNA copy of the gene is produced. Because the DNA sequence in the gene is transcribed into an RNA sequence, this stage is called transcription. Transcription is initiated when the enzyme RNA polymerase binds to a special nucleotide sequence called a promoter located at the beginning of a gene. Starting there, the RNA polymerase moves along the strand into the gene (figure 12.1). As it encounters each DNA nucleotide, it adds the corresponding complementary RNA nucleotide to a growing mRNA strand. Thus, guanine (G), cytosine (C), thymine (T), and adenine (A) in the DNA would signal the addition of C, G, A, and uracil (U), respectively, to the mRNA.



Figure 12.1 RNA polymerase.

In this electron micrograph, the dark circles are RNA polymerase molecules synthesizing RNA from a DNA template.


When the RNA polymerase arrives at a transcriptional “stop” signal at the opposite end of the gene, it disengages from the DNA and releases the newly assembled RNA chain. This chain is a complementary transcript of the gene from which it was copied.


Translation: An Overview

The second step of the Central Dogma is the transfer of information from RNA to protein, which occurs when the information contained in the mRNA transcript is used to direct the sequence of amino acids during the synthesis of polypeptides by ribosomes. This process is called translation because the nucleotide sequence of the mRNA transcript is translated into an amino acid sequence in the polypeptide. Translation begins when an rRNA molecule within the ribosome recognizes and binds to a “start” sequence on the mRNA. The ribosome then moves along the mRNA molecule, three nucleotides at a time. Each group of three nucleotides is a codeword that specifies which amino acid will be added to the growing polypeptide chain, and is recognized by a specific tRNA molecule. The ribosome continues in this fashion until it encounters a translational “stop” signal; then it disengages from the mRNA and releases the completed polypeptide.


Key Learning Outcome 12.1. The information encoded in genes is expressed in two phases: transcription, which produces an mRNA molecule whose sequence is complementary to the DNA sequence of the gene; and translation, which assembles a polypeptide.