Many students of biology have difficulty making the transition from early descriptive courses to later mechanistic courses in molecular biology, because their first exposure to genetics did not provide a simple foundation for protein structure and function. Basic genetics concepts for molecular biology:
- Genes code for proteins, DNA sequences correspond to amino acid sequences
- Proteins are enzymes
- Enzymes produce phenotype
- Dominant alleles code for functional enzymes and produce phenotype
- Recessive alleles are dysfunctional and do not contribute to phenotype
Genes Code for Proteins
Each human chromosome is a DNA molecule with about a thousand genes written into its sequence of nucleotides (A, T, G or C). The linear sequence of nucleotides for a particular gene is transcribed into a messenger RNA (mRNA) that is translated on a ribosome in the cellular cytosol into a corresponding linear sequence of thousands of amino acids. The amino acid chain, called a polypeptide or protein, coils and folds into a shape unique (minimal energy) for each protein.
Thus, most genes code for proteins and mistakes (mutation) during replication of the chromosomes produce changes in the amino acid sequence of the resulting proteins. Some of these proteins form structures such as ribosomes or the cytoskeleton, whereas others are enzymes.
Proteins Act as Enzymes to Produce Phenotypes
Metabolism of a cell results from catalysis of particular chemical reactions by enzymes that produce the catabolic and anabolic pathways, such as glycolysis, the tricarboxylic acid cycle, RNA transcription or protein synthesis. The physical appearance of a cell is the consequence of its proteins and other components, such as lipids and carbohydrates synthesized by proteins acting as enzymes. Thus, genes code for proteins and the proteins/enzymes in turn produce phenotype.
Dominant Alleles Code for Functional Proteins and Recessives Are Defective
Many early examples in genetics involve genetic traits for flower or eye color. The genes for these traits code for enzymes in pathways that convert a colorless molecule into a colored pigment, e.g. a red flower or the red eyes of fruit flies. In these cases each of the parent organisms had two copies of the pigment gene and each parent contributed one of those copies to the offspring.
There are also usually two different alleles for a given trait, e.g. red or white eyes, R or r. These are historically called dominant and recessive, consistent with the mistaken idea that there is an interaction between the two alleles.
Actually, the dominant allele simply codes for a functional enzyme, whereas the recessive allele is defective DNA sequence and even if it codes for a protein, that protein folds improperly and doesn’t function as an enzyme.
Dominance is a misnomer. If there are two defective copies, homozygous recessive, no functional enzyme is produced and in the example, the flower or fruit fly would lack red pigment and be white.
ABO Blood Group Antigens Are Carbohydrates Assembled by Enzymes
Another common example used in basic genetics is the red blood cell ABO antigens. These antigens are a short series of sugars that are added one sugar at a time in the Golgi apparatus of a cell before the resulting oligosaccharide is hung outside the cell on a short lipid tail embedded in the cell membrane.
The enzymes coded by the two dominant alleles, A and B, in this complex system are present in the Golgi and are responsible for attaching two alternative sugars, A (N-acetyl galactosamine) or B (galactose) to a short chain of sugars called O. If neither of the dominant alleles is present, i.e. both copies are dysfunctional or recessive, then neither sugar is added and the O short chain carbohydrate will remain.
If both allele A and allele B are present, then in some cases sugar A will be added by enzyme A and in other cases sugar B will be added by competing enzyme B. Both types of short carbohydrates (oligosaccharides) will be present on the surface of the red blood cells of the AB individual.
Dominance Means Functional Enzyme Produces Phenotype
Molecular biology explains how genes can provide the molecular information, sequences of nucleic acid bases or protein amino acids, to produce enzymes that can catalyze the reactions of cells. It is the consequence of these reactions that produces phenotypes. Thus, molecular biology shows the relationship between genotype and phenotype by simply stating that a dominant allele codes for a functional enzyme.
Refrences:
Alberts, B. et al. 2008. Molecular Biology of the Cell, 5th ed., Garland Science.
Campbell, N.E, et al. 2007. Biology, 8th ed., Benjamin Cummings.
Join the Conversation