The spectacular recent progress in genetics is the result of accumulated knowledge in several branches of biology and biochemistry that are the fruit of long years of basic research.
I. FROM THE ORGANISM TO THE GENE
CHROMATIN
|
CELL DIVISION
|
The distinct R groups possess different chemical
properties (acidic, basic, polar, non-polar, etc.) that provide for a wide range of structures capable of fulfilling
the various requirements of protein. A
table of the 20 amino acids is presented
with their names, 3 and 1 letter abbreviations, chemical structure of their R-group, and specific triplet codons
in the genetic code.
There are 64 codons, the maximum number for triplets
with four letters U, C, A, and G. These bases are the forms found in mRNA, the molecules formed in the transcription
process that resemble one strand of DNA and participate directly in the translation into the amino acid sequence
of proteins. As in the case of DNA, the mRNA molecules contain the bases cytosine (C), adenine (A), and guanine
(G), but each thymine (T) in DNA is replaced by a uracil (U) in RNA, where the letters in parenthesis are the standard
abbreviations. Several amino acids have many codons (6 for arginine and leucine), while others only have one (tryptophan
and methionine). Moreover, the codon for methionine, AUG, also signals the beginning of a coding sequence. In this way, a sequence of amino acids is generated
that is co-linear with the sequence of bases in the DNA. However, while the DNA sequence is functional in its linear
form, the protein only becomes functional when the amino acid sequence spontaneously folds into a specific three-dimensional
structure. It is only the final three-dimensional form that is capable of binding its substrate (if it is an enzyme)
or a hormone (if it is a receptor) because of the specific binding pockets that are created when distant regions
of the polypeptide come into proximity during the folding process. How the sequence of amino acids achieves the
proper folding into its three-dimensional form remains poorly understood. Indeed, reading the linear DNA sequence
is relatively simple compared to the possibility of using the amino acid sequence to deduce the final three-dimensional
form that the protein will take. In fact, the known three-dimensional structures of proteins were established by
experimental methods using X-rays on protein crystals, or nuclear magnetic resonance (RMN) on concentrated solutions
of purified proteins, and cannot be "predicted" merely on the basis of the amino acid sequence. |
Related Current Themes
Related Techniques
|
What is the genetic code?
codes for the amino acid sequence:
|
How is transcription achieved?
Part of the identification of where genes begin and end on DNA involves identifying which strand corresponds to the coding information and which is the complementary template. In the above example for hemoglobin, the upper strand carries the information that corresponds to the amino acid sequence of the hemoglobin subunit and this information will be transcribed into RNA by using the lower strand as the template, producing a messenger RNA molecule with the structure:
This sequence would produce the corresponding protein according to the assignments of the Table of the Genetic Code (which presents the 64 possible mRNA triplets and the corresponding amino acid encoded by each triplet):
Many genes, particularly in eucaryotic organisms,
are interrupted by non-coding sequences (called introns) that separate the portions of the gene (called exons)
that actually code for the sequence of amino acids in the protein. When the DNA is transcribed to yield messenger
RNA (m RNA), the introns are also copied. However, in a subsequent step the mRNA is processed (in a procedure called
"splicing") to eliminate the introns, so that the mature mRNA no longer contains the non-coding intron
sequences. The various steps of transcription and translation are summarized schematically in the diagram below:
|
What is a mutation? A mutation is any change that occurs in the DNA. It can be of the simplest form, a point mutation, that replaces a single base (A, T, G, or C) by a different base, or it can involve more complex changes, including insertions of one of more bases, deletions of many bases, or major rearrangements of a substantial portion of a chromosome. Changes of this type account for the variations that led to the evolution of the multitude of species found among the varied forms of life on our planet. Mutations can alter the specific structure of protein and RNA molecules, when the mutations lie within one of the regions of the chromosome (known as genes) that specify these structures. However, for a typical human chromosome, genes make up only about 3% of the total DNA sequence, but mutations in the intervening regions can greatly influence timing and expression of the genes. What are the effects of mutations? Mutations can occur at low frequency whenever DNA replicates during cell division. If they occur in the cells producing eggs or sperm, they will be transmitted to every cell of the next generation, whereas in other cells, "somatic" mutations will only effect tissues derived from the mutated cell (as occurs for certain forms of cancer) and will not be transmitted to the next generation. In general, every individual possesses many mutations compared to the "average" human being; most have no significant consequences and are considered "neutral". Others may lead to certain characteristics or susceptibilities that are considered to be part of the unique characteristics of a normal individual. Some are recessive mutations that would cause pathological conditions in a homozygous state (if they were present on both members of a pair of chromosomes), but are harmless in the heterozygous state (present on just one member of a pair of chromosomes). However, such latent recessive mutations are a reason that consanguinity within a family or within in a small population can have dangerous consequences for future generations. Some mutations are dominant and can provoke a genetic disease even when present on one chromosome. Recent studies have identified a novel type of mutation that involves repetitions of certain 3-base sequences (triplets) up to thousands of times. A small fraction of individuals in the human population are born with such a mutation that can cause a serious disease, for example " fragile X syndrome "or "severe myotonic dystrophy". Thousands of such diseases have been identified, but many occur in a just a few families in the world. What is special about mutations on the X or Y chromosomes? Among the 46 chromosomes, humans possess 22 pairs plus X and Y. Females are XX and males are XY. As a result, a male inherits only one X chromosome (from the mother) and if that chromosome harbors a recessive mutation in the mother, the mutation will appear "dominant" in the son, as in the case of hemophilia. Hence, each son of such a mother has a 50% chance of receiving the X chromosome with the mutation. Other genetic diseases lying on the Y chromosome are passed only from father to son. What causes mutations? Mutations occur spontaneously at a low, but finite rate. Whenever DNA is duplicated there is a tiny probability that an error will occur. In addition, the mutation rate may be increased by several factors, including radiation (one of the consequences of Hiroshima and Tchernobyl). Certain chemical pollutants in the environment possess mutagenic activity. UV light is also mutagenic and is the principal cause of skin cancers, principally due to mutations that inactivate the protein p53 that normally participates in cell growth control. Many other forms of cancer are caused by mutations in genes that produce abnormally active (or constitutive) proteins. |