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Reading the Messages in Genes

Biotechnology Industry Organization (BIO). "Biotechnology in Perspective." Washington, DC: Biotechnology Industry Organization, 1990.

The implications of the double-stranded structure of DNA are far-reaching, and were immediately obvious to Watson and Crick when they presented their model in 1953. As they described it, each DNA strand is precisely complementary to the nucleotide sequence of its partner strand, and consequently both contain the same genetic information. If the two strands are designated A and B, then A can serve as a mold or template for B, and vice versa. Genetic information is copied by a process in which strands A and B separate and unwind, enabling each separated strand to become a template for a new complementary partner strand. The result is that in both offspring of a divided cell, each DNA molecule has one original strand and one newly synthesized strand. This mechanism of semi-conservative replication ensures precise copying of the nucleotide base sequences in DNA.

The Genetic Code

A typical animal cell contains a meter of DNA. Each nucleotide, A,C,T, or G can be regarded as a letter in a four-letter alphabet used to write messages in the form of a kind of linear (biological) coded tape. So the number of possible sequences in an animal cell would fill several thousand books with continuous text. Much less DNA is found in the virus X174, which infects bacterial cells and whose complete DNA sequence can be written on a single page. The principles of gene replication are readily intelligible, but the biochemical machinery by which this copying mechanism takes place is complex and involves many enzymes.

In the early 1960s, the genetic code was cracked. An adjacent group of three nucleotides (triplets) was shown to code for an amino acid. With 20 amino acids and 64 possible triplets, most amino acids are specified by several triplet 'codons.' The genetic code is universal and is the same in organisms as diverse as viruses, bacteria, plants, animals, and man. It is this universality of the genetic code that permits a bacterial cell into which a section of mammalian DNA has been transferred to make perfect sense of the incorporated message. Without this universality, much of modern biotechnology would not exist.

Errors Lead to Mutations

Unraveling the genetic code demonstrates the need for precision in DNA replication. Errors in a particular codon could lead to the wrong amino acid being specified at some point in a protein molecule. This could result in a shape change sufficiently dramatic to change the function of that protein. Errors in replication, and those induced by external agents such as prolonged exposure to UV, X-rays, and radioisotopes, are known as mutations.

Organization of DNA in Cells

The DNA in a bacterial cell forms a single loop-like structure, whereas in animal and plant cells separate molecules of DNA (chromosomes) can be identified. These are complex structures, each containing many genes and packaged with closely associated DNA binding proteins (the histones). Associated proteins are important in regulating gene activity in cells. Many of the recent developments in our knowledge of DNA sequences encoding for specific proteins have stemmed from the elegant sequencing procedures devised by Fred Sanger and his colleagues in Cambridge, England.

Proofreading the Code

Decoding the base sequence of DNA to make proteins is a complex process with built-in molecular checks and safeguards to ensure that the instructions are correctly read. The cell is also actively at work to preserve the accuracy of the DNA code and eliminate errors. It was the physicist Erwin Schrodinger who pointed out in 1945 that the observed complexity of living organisms requires that individual genes consist of very few atoms so that the genome can be accommodated in a cell.

Because of its size, a gene would be expected to undergo significant changes due to random spontaneous reactions arising from thermally induced collisions of molecules. The dilemma is real. It may come as a surprise to learn that there are several thousand errors induced in your DNA each day! No need to panic, however - some 20 different enzymes are at work continuously proofreading and eliminating these errors. The repair mechanisms all depend on the existence of two copies of the genetic information - one on each strand of the DNA. Thus, mutations are relatively rare, although their presence at low frequency contributes to their variation in populations of organisms, which is essential to evolution.

Copying and Translating Genes

Protein synthesis using the blueprint contained in the DNA sequence of nucleotides in the form of the genetic code is achieved by first copying particular regions of DNA into a chemically and functionally different kind of polymer known as 'messenger' ribonucleic acid (RNA). The coding section of DNA that is copied contains the gene for a specific protein, and it can be copied many times. Like DNA, RNA is a linear sequence of nucleotides, but there are two minor chemical differences. First, the sugar-phosphate backbone of RNA contains ribose instead of a deoxyribose sugar. Second, the base thymine (T) is replaced by the closely related base uracil (U). Additionally, no complementary strand is present.

Transcription of the Code

RNA retains faithfully all the information of the original DNA sequence, and the process of RNA synthesis is known as DNA transcription. It shares some common features with DNA replication itself, in that the first step is the opening up of the DNA double strand in the region to be copied. Then one of the two strands of DNA acts as a template for the synthesis of RNA.

Here the similarities end. There are several essential differences between DNA and RNA synthesis. For example, the RNA strand does not stay attached to the DNA. As soon as the copy is completed, the DNA double-stranded helix reforms and the RNA is released as a single strand. RNA molecules are also much shorter than DNA itself, representing only a minor fraction of the genome. The production of RNA from a single gene can be carefully controlled by the cell - this is achieved by gene regulatory proteins, and this regulation of gene copying is important in controlling the differentiation and development of cells in all complex multicellular organisms.

A Messenger Molecule

Many thousands of RNA copies can be run off from the same DNA segment during each cell generation. In the cells of higher organisms, many of these RNA molecules undergo major changes before leaving the nucleus to act as messenger molecules (mRNA) that direct the synthesis of proteins. Translation of the mRNA molecules takes place in the cell cytoplasm at specific protein synthesizing stations called ribosomes. These particles are barely discernible in the electron microscope, and their fine structure is slowly being unraveled. Composed of RNA and proteins, ribosomes allow the message to be decoded and enable assembly of the building blocks of proteins (amino acids) in their correct sequences.

Translation of the Code - Protein Synthesis

Three nucleotides (a codon) encode a single amino acid and, though there are specialized start and stop sequences, the bulk of an mRNA molecule is made up of a linear sequence of codons each specifying an amino acid. The mRNA tape is threaded through the ribosome like punch tape and the appropriate amino acids are added to the growing protein molecule.

However, the mRNA do not directly recognize the amino acids that they specify, in the way that an enzyme recognizes a substrate. The process of translation employs adaptor molecules that recognize both an amino acid and a group of nucleotide bases. These adaptor molecules are a family of RNA molecules known as transfer RNAs (tRNAs), each of which is between 70 and 90 nucleotides in length and with a looped structure produced by folding of the tRNA single strand. This characteristic shape is essential to its functional role as an adaptor.

Of special importance are two sets of three unpaired nucleotide residues in the tRNA molecule. One of these triplets forms the anticodon region which can base-pair to a complementary triplet in mRNA. A triplet at the free end of the tRNA molecule is attached to a particular amino acid. With a separate tRNA for each amino acid, only the tRNA carrying the correct amino acid can bind to the section of mRNA exposed for translation on the ribosome. By threading the mRNA codons in sequence through the ribosome, tRNA molecules bind successively and add their amino acid cargoes to the growing protein until it is complete. When the ribosome reaches the end of its message, both message and protein are released.

Go to Graphics Gallery: The Structure of DNA, DNA Replicating Itself, RNA and DNA,
Protein Synthesis

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