UNIT 3: Molecular Genetics

Chapter 7: Genes and Proteins Synthesis 7.1: From Gene to Protein

pg. 310 pg. 312 - 318

One gene-one enzyme hypothesis - is the hypothesis, proposed by Beadle and Tatum; that each gene is unique and codes for the synthesis of a single enzyme. One gene-one polypeptide hypothesis – is the hypothesis that each gene is unique and codes for the synthesis of a single polypeptide; the restated version of the one gene-one enzyme hypothesis. Archibald Garrod (1896) studied Alkaptonuria, a human disease easily detected when a patient’s urine turns black in air. Garrod determined that alkaptonuria was an inherited. By 1908 he determined the disease was caused by a mutation in a gene that normally codes for an enzyme to breakdown tyrosine. If tyrosine is not broken down then alkapton accumulates. Beadle and Tatum (1940’s) studied bread mould, Neurospora crassa. Their data supported the relationship between genes and enzymes. The mould was able to grow in a minimal medium (MM). The moulds were able to synthesis the more complex molecules for survival. They then x-rayed spores form Neurospora crassa, and then observed them in the minimal medium. The mould was unable to grow. They suggested that the x-rays mutated the genes; therefore the spores could no longer produce the complex molecules to survive. The mutated strain could resume growth if arginine was present. The production of arginine is a multi-step process, with multiple enzymes required, one for each step. Their conclusion stated that one gene-one enzyme hypothesis. The hypothesis was later expanded to one gene-one protein, because not all amino acids assembled create enzymes.

Connection between DNA, RNA, and Protein Central dogma – is the fundamental principle of molecular genetics, which states that genetic information flows from DNA to RNA to proteins.

Figure 2: The central Dogma of molecular genetics states that genetic information flows from DNA to RNA to Protein.

Transcription – is the mechanism by which the information coded in nucleic acids of DNA is copied into the nucleic acids of RNA; something rewritten in the same language. Translation – is the mechanism by which the information in the nucleic acids of RNA is copied into the amino acids of proteins. Francis Crick (1956) gave the name “central dogma” to the progression from DNA to RNA to protein. There are two major steps to this progression; transcription and translation.

RNA – Ribonucleic Acid Messenger RNA (mRNA) – is the end product of the transcription of a gene; mRNA is translated by ribosomes into protein. Transfer RNA (tRNA) – is a carrier molecule that binds to a specific amino acid and adds the amino acid to the growing polypeptide chain. Ribosomal RNA (rRNA) – is an RNA molecule within the ribosome that bonds to correct amino acid to the polypeptide chain. Ribonucleic acid is a carrier of genetic material like DNA. RNA molecules are different from DNA because they are single stranded, contained uracil other then thymine, and had a ribose sugar group.

Table 1: Comparison of DNA and RNA Deoxyribonucleic Acid - double stranded - adenine pairs with thymine - guanine pairs with cytosine - deoxyribose sugar

Ribonucleic acid - single strand - adenine pairs with uracil - guanine pairs with cytosine - ribose sugar

Figure 3: DNA and RNA are similar, with a few important differences: RNA is single stranded, not double stranded; RNA has Uracil in place of Thymine in DNA, and RNA contains a hydroxyl group (OH) at the 2′ position of the sugar, whereas DNA has hydrogen (H) at that position (thus “deoxy” to denote the absence of Oxygen).

There are three major types of RNA participate in protein synthesis; messenger RNA, transfer RNA, and ribosomal RNA.

Table 2: Different Types of RNA Type of RNA Messenger RNA (mRNA)

Transfer RNA (tRNA) Ribosomal RNA (rRNA)

Characteristics and key functions - varies in length, depending on the gene that has been copied - acts as the intermediary between DNA and the Ribosome - is translated into protein by ribosomes - is the RNA version of the gene encoded by DNA - Functions as the delivery system of amino acids to ribosomes as they synthesize proteins - is very short, only 70 to 90 base pairs long - binds with proteins to form the ribosomes - varies in length

Figure 4: tRNA is composed of a single strand of RNA that loops in on Itself to form antiparallel double-stranded areas.

Transcription and Translation: An Overview RNA polymerase – is an enzyme that reads a DNA strand and creates a complementary strand of RNA. Template strand – is the DNA strand that is copied into an mRNA molecule during gene transcription. Precursor mRNA (pre-mRNA) – is the initial RNA transcription product. Transcription is the first step in protein synthesis. RNA polymerase is used to synthesize a RNA molecule, using complementary base pairs to one strand of a DNA molecule. The DNA template strand is read 3′ to 5′ direction, as the RNA strand is built in the 5′ to 3′ direction. The DNA template strand (code) is read by RNA polymerase to transcribe a precursor mRNA molecule. The pre-mRNA molecule is not used to produce a protein; it must be modified before it exits the nucleus. After the modified mRNA molecule leaves the nucleus and enters the cytosol and binds with a ribosome, translation can begin. The ribosome moves along the mRNA reading the codon (3 nitrogen bases). tRNA is responsible for retrieving amino acids that are identified by the codon, which is complementary to the anti-codon of the tRNA molecule. The tRNA delivers the appropriate amino acid to the ribosome to be bonded to the adjacent amino acid, forming a polypeptide chain. The number and sequence of amino acids are determined by the gene.

Figure 5: the relationship between a gene, the codons in an mRNA, and the amino aid sequence of a polypeptide.

The Genetic Code: Three-Letter Words with a Four –Letter Alphabet Genetic code – is the specific coding relationship between bases and the amino acids they specify; genetic code can be expressed in terms of either Codon – is a group of three base pairs that code or an individual amino acid. Start Codon (Initiator Codon) – is the codon that signals the start of a polypeptide chain and initiates translation. Stop Codon – is a codon that signals the end of a polypeptide chain and causes the ribosome to terminate translation. The genetic code determines the amino acid number and sequence during protein synthesis. The DNA alphabet consists of four letters combined in groups of three letters to code for an amino acid. The four letters represent the nitrogenous bases found in the DNA molecule, A (adenine), G (guanine), T (thymine), and C (cytosine).

During transcription an mRNA molecule is produced based on the code for a gene found in a strand of DNA. RNA has an alphabet made up of four letters representing nitrogenous bases; A (adenine), G (guanine), U (uracil), and C (cytosine). Once again only three letters are used to code for an amino acid. There are sixty four (43) different combinations of three nitrogenous bases that can code for 20 amino acids. Some of the amino acids have more then one codon to represent them. 61 codons code for amino acids, while 3 codons code for a stop codon (UAA, UAG, UGA) in the protein sequence, (a period within a sentence).The codon (start codon) AUG codes for the first amino acid in protein synthesis, known as Methionine. The genetic code is universal in most organisms or viruses, which code for the same amino acids. This indicates that the genetic code was established in an early time in the evolution of life and remains unchanged.

Figure 7: The Genetic Code, written in the form in which the codons appear in mRNA; The AUG initiator codon, which codes for Methionine, is shown in yellow; the three terminator codons are shown as STOP. The triplet sequences are in the 5′ to 3′ order.