Nitrogenous bases occur one per nucleotide. These bases are divided into two categories based upon the structure of the carbon ring or rings: purines, which are the double-ringed bases adenine and guanine, and pyrimidines are the single-ringed bases cytosine, thymine, and uracil. These bases are complementary, in that, purines can form specific chemical bonds with pyrimidines. Adenine will chemically bond either to thymine or uracil. Guanine will bond only to cytosine. DNA contains the nitrogenous bases adenine, cytosine, thymine and guanine. RNA contains adenine, cytosine, and guanine, but contains uracil instead of thymine. The dual bonding ability of adenine, and single bonding specificity of the other nucleotide bases assures that information can be passed from DNA to RNA in a very precise, non-random fashion, and that when DNA replicates itself before the cell divides, each new daughter cell receives exactly the same set of genetic instructions.
The subunits of nucleic acids can also be utilized
by the cell to perform functions other than those of information storage
and retrieval. If adenine is bonded to ribose and three phosphate
groups, it is called adenosine triphosphate (ATP), the primary energy storage
molecule of the cell. Guanine can also form such a molecule, guanosine
triphosphate (GTP), which serves a similar role.
Before the reproduction of a cell, eukaryotic chromatin condenses into thick bodies called chromosomes, which are easily seen with a compound brightfield microscope after staining with chromic acid. In prokaryotes, DNA strands are connected into a loop referred to as the bacterial chromosome, or into smaller, extrachromosomal loops called plasmids. The bacterial chromosome is so named due to convention- it is only visible under electron microscopy due to the small size of bacterial cells.
RNA molecules are similar in structure to DNA, but they contain the sugar ribose, they are single stranded molecules, and they contain the nucleotide base uracil instead of thymine. Ribosomes are constructed from a DNA template (a short segment of one of the nucleosides of DNA) during the process known as transcription.
The information stored in DNA molecules is vital to the ability of the cell to produce the proteins which are necessary for proper metabolic functioning. If a cell which has been produced through cell division lacks these instructions, it is incapable of survival for an extended period of time. For example, mature mammalian red blood cells (erythrocytes) lack a nucleus. Though they do carry enzymes neccessary to their proper functioning, they cannot synthesize more, so after about 120 days of life, they die and must be replaced.
The process of DNA replication involves the
use of many enzymes. Enzymes catalyze the separation of the two helices
of DNA, then DNA polymerase bonds new complementary strands together
at a rate of about 100 nucleotides per second. In prokaryotes,
DNA is unwound by helicases, kept unwound by single-strand binding
proteins, and wound by DNA gyrase. The process of DNA replication
occurs as follows. Helicases break the hydrogen bonds between the
complementary base pairs. This process occurs along a line called
the replication fork, since DNA is not completely separated before replication
begins. New nucleotides are constructed outside of the nucleus and
are transported through the pores in the nuclear envelope.
These new nucleotides are ligated (bonded) to each original strand
of the separated molecule, such that each new nucleoside is an exact copy
of the opposite original. This process occurs until the entire strand
of the DNA molecule has been replicated. This process is discontinuous,
since DNA polymerase bonds new nucleotides from the 5' to 3' direction.
The nucleoside which begins at the 3' (P) end is started by an enzyme called
primase, which functions by adding a short section of about
five RNA nucleotides which act as a primer for the process to begin.
However, the strand is only partially constructed by DNA polymerase, leaving
small finished portions called Okazaki fragments. The unfinished
fragments are completed by DNA ligase ultimately binding to their
nucleotide complements and finishing the new daughter strand. Because
each of the nucleosides of the original DNA molecule compose one side of
the two new molecules, DNA replication is referred to as a semi-conservative
process. The process of DNA replication must occur before
each new molecule can condense into chromosomes and cell reproduction can
continue. This process occurs during a period known as the S-phase
(synthesis phase) of the cell cycle.
These bases temporarily bond to their complementary DNA bases as the sugar- phosphate backbone is constructed at a rate of about 60 nucleotides per second (Remember, uracil bonds to adenine) through the activity of RNA polymerase. When the complete molecule is formed, it is enzymatically separated from its DNA template. This new molecule is called messenger RNA (mRNA), because it carries the message about how a protein is to be constructed.
The next phase of protein synthesis, called translation, occurs outside of the nucleus of eukaryotes,and in the cytoplasm of prokaryotes. mRNA travels out of the nucleus to either the cytoplasm, or to the rough endoplasmic reticulum. The "message" carried by the mRNA molecule is composed of sequences of three nucleotide bases called codons. Each codon codes for one of the twenty amino acids. The number of codes which can possibly be produced during transription is limited, because there are only four nucleotide bases in DNA, such that, if all of the possible three-letter codons were written from a strand of DNA, only 64 possible combinations could be produced. As a consequence, much of the DNA molecule is composed of the same sequences of codes. Because of this, the structure of the DNA molecule is often said to carry a redundant code. However, when these combinations are placed along a strand of DNA such that, when transcribed into an RNA molecule they carry information for the production of a new protein, they are referred to as a gene.
Once outside the nucleus and at the site of protein
translation, mRNA is joined by molecules of transfer RNA (tRNA).
tRNA moleules have a cloverleaf shape, and have several active sites where
chemical bonding can occur. On one end of the tRNA molecule is a
site which bonds specifically to one amino acid. On the other, there
is a sequence of three nucleotide bases called an anticodon.
The process by which amino acids are joined to the tRNA molecule is catalyzed
by enzymes called aminoacyl-tRNA synthetases.
While there are 64 possible combinations of mRNA codons, only about 40 tRNA molecules exist in nature. This is because some tRNA molecules can bind to several different mRNA codons which specify for the same amino acid. The reason for this lies in the ability of the third tRNA (3') nucleotide on an anticodon to bond to more than one type of complement (example- U bonding to either A or G) on the corresponding (5') portion of an mRNA codon. This phenomenon is called wobble.
Ribosomes are produced in the eukaryote nucleolus or prokaryote cytoplasm. They are a combination of protein and ribosomal RNA (rRNA), and serve to catalyze the process of translation. When mRNA and tRNA are brought together, they join specifically, codon to anticodon, forming temporary hydrogen bonds between their complementary nucleotide bases. Ribosomes move across the surface of the mRNA/tRNA complex, simultaneously linking amino acids together by joining them through dehyrdation to form C-N peptide bonds, and breaking the bonds between amino acid, tRNA, and mRNA. The tRNA molecules move back into the cytoplasm to bond with new amino acids, then return to begin the process again. In prokaryotes, large numbers of ribosomes often line up on the mRNA strand to form polyribosome complexes.
The process begins and ends differently when considering prokaryotic cells and eukaryotic cells. Genes in prokaryotic cells are linked end to end in the bacterial chromosome. At the beginning of each prokaryotic gene strand is a sequence of nucleotides called the promoter, which lies just ahead of a sequence called an initiation code which has the pattern TAC (thymine-adenine-cytosine). At the end of the gene is a sequence called a terminator region, which may have one of three possible code patterns; ATT, ATC, or ACT. These codes, when transcribed into their mRNA equivalents tell the ribosome when to start and stop translation. In the eukaryotic cell, however, there is a different system. There are both promoter and termination sequences, but along the DNA molecule, there are sequences of base pairs called exons, which contain meaningful information, and introns, which are sequences which contain meaningless sets of instructions. Because of this, RNA polymerase first transcribes a molecule called pre-RNA, containing both exons and introns, then removes the introns to form mature mRNA, before translation can begin.
Since DNA is redundant in its code, and there are only twenty
naturally occurring amino acids, it is possible to produce an mRNA dictionary
which gives precised codon sequences for each amino acid in a polypeptide.
Knowing this, it is also possible to sequence the complementary DNA nucleotides
necessary for the production of each protein. Given this information,
scientists can now begin the process of learning the structure of each
gene, ultimately to learn the entire set of genes or genome, of living
organisms. One of the newly emerged applications of this knowledge
is the science of genetic engineering.
A change to a single nucleotide base is called a point mutation. An example of this is the disease known as sickle-cell anemia. In this disease, a single nucleotide of the gene which controls the production of hemoglobin is altered, causing the blood cell to form a sickle-shape which prevents the normal ability of the cell to acquire oxygen. Such mutations can be caused by either the insertion or deletion of a nucleotide or nitrogenous base, leading to a frame-shift in the sequence of nucleotides. Ultimately, this can affect the cell in that the sequence of amino acids in a polypeptide code for by the altered DNA is disrupted.
If a segment of DNA moves from one part of the DNA molecule to another, it is called a transposon or "jumping gene" and can cause changes in the whole molecule. Some pathogens such as Trypanosoma gambiense and Plasmodium malariae have the ability to change the placement of the antigens on their cell surfaces due to transposon activity, thus can overcome host immune defenses.
Changes in chromosome structure or number are called chromosomal mutations. One example of a chromosomal mutation is called nondisjuction, which occurs when chromosomes do not segregate properly during cell division. In humans, nondisjuction can lead to such birth defects as Down's Syndrome, Turner's Syndrome, and Kleinfeldter's Syndrome. Mutations; however, are not always detrimental. If the changes in the genome of an organism which are beneficial select that organism for survival, they will be passed along over generations, changing the overall gene pool, or genetic makeup of populations. This, in turn, leads to the evolution of species.
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