Cellular Information Processing and Genetics
The Concept of Information Processing in the Cell
Cells are controlled by genes (blueprints) in chromosomes.
These genes contain information for synthesizing specific proteins.
Proteins determine the structural and functional characteristics of the cell or organism.
Modern molecular biology focuses on:
How information is encoded in the chromosome.
How the information is processed.
How the blueprint replicates during cell division.
How the information can be modified to provide new message material.
Regulation and control of information transactions are an important aspect of molecular biology.
DNA properties explain information encoding, processing, replication, and mutability.
DNA directs the cell's destiny and maintains genetic continuity between generations.
In some viruses, RNA takes the central informational role.
DNA creates a messenger molecule (mRNA) of complementary structure.
DNA is protected in the nucleus (in eukaryotes) from the cytoplasm's dangers.
Transcription: Production of mRNA from a DNA template.
Translation: mRNA joins ribosomes and other molecules to synthesize a protein.
The code for assembling amino acids into a protein is transcribed from DNA to RNA and then translated into a protein.
DNA replicates during cell division to pass information to the next generation.
High fidelity is required during encoding, transmitting, and replicating information to ensure coherent protein production.
Mutations: Physical alterations in DNA that lead to changes in the coded sequence that provide new genetic sequences for evolution.
The Search for the Chemical Bases of Inheritance
Friedrich Miescher isolated "nuclein" (nucleic acid, later known as DNA) from cell nuclei.
Walther Flemming stained chromosomes during mitosis, describing cell division.
Theodor Boveri described meiosis, which reduces chromosome number from 2n to n in gametes.
C. B. Bridges' experiments showed chromosomes are the physical basis of inheritance.
Robert Feulgen developed a method for staining DNA and found it is primarily in chromosomes.
P. A. Levene worked out the chemical properties of DNA in the 1920's.
The basic unit of DNA is a nucleotide; consisting of a phosphate group, a 5-carbon sugar (deoxyribose), and a nitrogenous base.
Nitrogenous bases: two purines (adenine, guanine) and two pyrimidines (thymine, cytosine).
Levene proposed DNA was a tetranucleotide with four nucleotides joined together; each containing a different nitrogenous base.
He thought the four bases were present in equal amounts.
This simple structure led scientists to mistakenly conclude DNA could not be the primary material for heredity and the control of cellular metabolism.
Erwin Chargaff showed that the four common bases of DNA are not present in equal parts but instead demonstrate considerable variation.
The repertoire of variation is consistent with the possibility that DNA is the blueprint material of the cell.
The amount of adenine (A) always equals the amount of thymine (T) and the amount of guanine (G) always equals the amount of cytosine (C).
A = T and G = C
The total amount of purines (A + G) is equal to the total amount of pyrimidines (T + C).
A + G = T + C
The amount of DNA in somatic cells is constant, while gametes have half the total amount.
Evidence implicating DNA:
Pneumococci transformation is altered by DNA of a second strain.
Viruses multiply by subverting a bacterial cell's protein-synthesizing machinery.
Sexual recombination of bacteria involves DNA manipulation.
DNA’s Secret Is Unraveled: The Double Helix
Watson and Crick developed a model for DNA structure using x-ray diffraction photographs by Rosalind Franklin. DNA is double-stranded; each strand is a helix, and the two strands are entwined around one another. One complete coil is 10 bases long.
DNA is like a twisted ladder with alternating sugars and phosphate groups as sides.
Bases jut out of each sugar; a base from one strand is hydrogen bonded with a base from the adjoining strand, forming the rungs of the ladder.
DNA may exist in at least four geometric formations:
B-DNA: the form described by Watson and Crick.
A-DNA: a partially unwound form.
C-DNA: a tightly coiled, compact configuration.
Z-DNA: helix wound opposite in direction to B-DNA with a zigzag shape.
Hydrogen bonding and hydrophobic interactions hold the double helix together.
Adenine is always cross-linked with thymine (two hydrogen bonds), and cytosine is always linked with guanine (three hydrogen bonds).
Adenine and thymine are complementary bases, as are guanine and cytosine.
This explains Chargaff’s findings that in DNA, A = T and G = C.
Each sugar is joined by a phosphate molecule at carbon atom 5 (C-5) to the sugar above and at C-3 to the sugar below.
One end of the strand with a free or phosphorylated carbon at the C-5 position is called the 5' end.
Encoding Information—The Language of the Gene
Watson and Crick published their DNA model in 1953, starting molecular biology.
The search began to understand how DNA structure accounts for information encoding, processing, replication, and alteration.
George Gamow realized that the code must have a minimum of 20 different “words” (codons) to account for the arrangements of the 20 naturally occurring amino acids.
The arrangement of bases along the strands is the encoding mechanism.
One base codons are insufficient (only 4 combinations).
Two base codons yield only 16 combinations (4^2).
Three bases as the unit codon, we have 4^3, or 64, different arrangements possible.
Gamow hypothesized the triplet codon, and Crick demonstrated its operative validity.
The genetic code is a linear sequence of three bases, and appears to be universal.
It is degenerate (redundant): a number of different codons may represent the same amino acid.
Leucine has six codons: UUA, UUG, CUU, CUC, CUA, and CUG.
Some codons may be used as punctuation, i.e., starting or stopping signals.
Meaningful information is contained in only one of the strands of the double helix (sense strand).
The complement of it's respective codon on the sense strand.
Even though the complementary sequences may well code for amino acids, they will probably not be the same amino acids as coded for by the codons on the sense strand, and will thus place the wrong amino acids into the protein. However, for a different protein, the complementary strand may become the sense strand in another portion of the DNA.
Processing the Information—Protein Synthesis
Transcription: The information from DNA is transferred to messenger RNA (mRNA).
RNA is similar to DNA but is single-stranded and has ribose sugar instead of deoxyribose sugar; also, it uses uracil instead of thymine.
DNA acts as a template for arranging RNA bases.
The sequence begins with bases that will later permit the mRNA to attach to a ribosome.
It codes for the amino acid sequence of the protein that will be constructed.
It ends with a codon that will signal termination of the synthesis of the protein.
Unwinding proteins begin transcription by breaking the H bonds between complementary bases.RNA polymerase attaches to the promoter region of DNA.
Synthesis begins at the 3′ position of DNA with the creation of the 5′ end of RNA (an antiparallel arrangement).
Each base of the exposed DNA template attracts a complementary base from a pool of free bases in the nuclear sap.
These free bases exist as the nucleotide triphosphates ATP, GTP, UTP, and CTP, and so contain a great deal of energy, which facilitates their assembly (polymerization) into a polynucleotide.
The nitrogenous base of each nucleotide hydrogen bonds (according to the base pairing rule) to its complementary base on the DNA sense strand.
RNA polymerase catalyzes the attachment of the nucleotides to each other to form a strand.
Complementary RNA codons are built upon a DNA template and then joined into a single-stranded RNA molecule.
A termination signal marks the 3′ end of the finished mRNA molecule, which is released and migrates out of the nucleus.
The direction of RNA synthesis is 5′→3′.
Many copies of mRNA will be formed, depending on the number of protein molecules to be manufactured.
The transcription process in eukaryotes is complicated by the existence of long sequences of bases in DNA (introns) that do not contain meaningful information for protein synthesis.
During transcription, both the introns and the DNA sections that are subsequently translated (exons) are transcribed into the mRNA.
In the nucleus, this slurry of primary transcripts is referred to as heterogeneous nuclear RNA, or hnRNA.
Before the mRNA leaves the nucleus, the sections representing the introns are excised and the remaining sections are annealed; this yields functional mRNA, which migrates out of the nucleus for the next stage of protein synthesis–translation.
Translation: The production of protein.
Requires ribosome, mRNA, and transfer RNA (tRNA).
tRNA carries amino acids to the mRNA for incorporation into the protein chain.
One end of each tRNA binds to a specific amino acid; the other end contains an anticodon.
The anticodon is a base triplet sequence that is complementary to one of the mRNA codons for the amino acid at the other end.
There are at least as many tRNAs as there are codons for amino acids.
Translation begins with mRNA migrating to the cytoplasm, where the 5′ end binds to the smaller (30 S) of the two subunits of a ribosome.
A tRNA with the appropriate anticodon is attracted to the starting position of the mRNA; at the same time, the tRNA attaches to the first of two binding sites on the larger (50 S) ribosomal subunit.
When the second binding site is occupied by a second tRNA-amino acid complex, the two respective amino acids are joined with a peptide bond produced by an enzyme (peptidyltransferase) located in the 50 S subunit.
The first tRNA molecule is then freed as the ribosome shifts over to the next codon.
This brings the second tRNA-amino acid complex into the first (P) site on the larger subunit and permits yet another tRNA to bring a third amino acid into position.
Each time the ribosome shifts to a new codon on the mRNA, the second (A) position is made available to, and filled by, the tRNA-amino acid complex appropriate to the codon being read.
The new amino acid is joined to the polypeptide chain, and the process is repeated.
When the ribosome reaches a termination signal, it releases the completed polypeptide chain.
Reproduction of Information—DNA Replication
Each strand of DNA can serve as a template for a complementary strand.
The double helix can unwind and separate, and the individual strands can attract their complementary bases.
Each original strand is associated with its complement, creating two identical double helices.
This is semiconservative replication: each double helix consists of one “parent” strand and one newly synthesized strand.
The double helix is unwound by Topoisomerases, Single-stranded DNA binding protein (SSB protein), and helicases.
Chain growth is initiated by a primase and is extended by a DNA polymerase.
Growth occurs in a 5′→3′ direction (i.e., from the 3′ end of the template).
Exonucleases can remove sections of DNA, and abutting segments of unjoined DNA can be annealed by ligases.
Modification of Information—Mutation
A change in the sequence of triplet codons is termed a mutation.
Insertion: An extra base is added, dropping the reading frame back one letter and changing all subsequent codons.
If the insertion occurs toward the end of the gene “tape,” then only one or several terminal amino acids would be affected and a functional, but slightly altered, protein would be produced.
Deletion: A base is deleted, advancing the reading frame one letter and changing all subsequent codons.
Substitution: One base is substituted for another, changing a single codon and substituting one amino acid for another.
Sickle-cell anemia is caused by the substitution of valine for the usual glutamine.
Transposition (jumping genes): Relatively long stretches of DNA jump from one chromosome to another.
Transposons are generally transferred as circular strips of DNA and are capable of producing the enzyme that enables them to intrude within the new chromosomal site.
Mutagens: Agents that cause mutations.
Chemicals and ionizing radiation (x-rays, cosmic rays, alpha, beta, and gamma rays).
Ultraviolet light also can cause mutation.
Genetic Engineering
Genetic engineering: Procedures to intentionally alter genetic information.
DNA recombinant procedures (gene splicing): Introducing foreign DNA into an existing genome.
The bacteria are, in a certain sense, part human because they are capable of producing a human protein.
Individual genes for human growth hormone and interferon have also been introduced into bacteria.
Major tools for recombinant DNA studies: Restriction enzymes (endonucleases), plasmids, and viruses.
Restriction enzymes act like scissors to cut DNA at precise regions.
A plasmid is a small circular piece of DNA outside the chromosome in bacteria and some yeast.
Foreign DNA is incubated with plasmids opened by restriction enzymes.
Viral particles can be used as a vector to bring foreign DNA into a bacterium.
Viral DNA is incubated with foreign DNA fragments and incorporates this foreign DNA into its genome.
Genetic engineering involving the whole genome: Melding (union) of nuclei from different species.
Cloning: Producing many copies of a single gene, chromosome, or whole individual.
Nonreproductive tissues are used; sexual recombination is not involved.
Cloning in carrots involved manipulating differentiated cells to return to an embryonic condition.
Cloning in vertebrates has been achieved in frogs by placing nuclei of mature cells into enucleated eggs.