Unit Three. The Continuity of Life
10. Foundations of Genetics
It is useful, before considering Mendelian genetics further, to gain a brief overview of how genes work. With this in mind, we will sketch, in broad strokes, a picture of how a Mendelian trait is influenced by a particular gene, how a gene can be altered by mutation, and the potential long-term evolutionary consequences of such an alteration. We will use the protein hemoglobin as our example — you can follow along on figure 10.11 starting at the bottom.
Figure 10.11. The journey from DNA to phenotype.
What an organism is like is determined in large measure by its genes. Here you see how one gene of the 20,000 to 25,000 in the human genome plays a key role in allowing oxygen to be carried throughout your body. The many steps on the journey from gene to trait are the subject of chapters 11 and 12.
From DNA to Protein
Each body cell of an individual contains the same set of DNA molecules, called the genome of that individual. As you learned in chapter 3, DNA molecules are composed of two strands twisted about each other, each the mirror image of the other. Each strand is a long chain of nucleotide subunits that are linked together. There are four kinds of nucleotides (A, T, C, and G), and like an alphabet with four letters, the order of nucleotides determines the message encoded in the DNA of a gene.
The human genome contains 20,000 to 25,000 genes. The DNA of the human genome is parcelled out into 23 pairs of chromosomes, each chromosome containing from 1,000 to 2,000 different genes. The bands on the chromosome in figure 10.11 indicate areas that are rich in genes. You can see in the figure that the hemoglobin gene is located on chromosome 11.
At the next level in the figure, individual genes are “read” from the chromosomal DNA by enzymes that create an RNA transcript of the nucleotide sequence (except U is substituted for T). This RNA transcript of the hemoglobin (Hb) gene leaves the cell nucleus and acts as a work order for protein production in other parts of the cell. But, in eukaryotic cells, the RNA transcript has more information than is needed, so it is first “edited” to remove unnecessary bits before it leaves the nucleus. For example, the initial RNA gene transcript encoding the beta-subunit of the protein hemoglobin is 1,660 nucleotides long; after “editing,” the resulting “messenger” RNA is 1,000 nucleotides long—you can see in the figure that the Hb mRNA is shorter than the RNA transcript of Hb gene.
After an RNA transcript is edited, it leaves the nucleus as messenger RNA (mRNA) and is delivered to ribosomes in the cytoplasm. Each ribosome is a tiny protein-assembly plant, and uses the sequence of the messenger RNA to determine the amino acid sequence of a particular polypeptide. In the case of beta-hemoglobin, the messenger RNA encodes a polypeptide strand of 146 amino acids.
How Proteins Determine the Phenotype
As we saw in chapter 3, polypeptide chains of amino acids, which in the figure resemble beads on a string, spontaneously fold in water into complex three-dimensional shapes. The beta-hemoglobin polypeptide folds into a compact mass that associates with three others to form an active hemoglobin protein molecule that is present in red blood cells. In the figure, each hemoglobin molecule binds oxygen (a process described fully in chapter 24) in the oxygen-rich environment of the lungs, and releases oxygen in the oxygen-poor environment of active tissues.
The oxygen-binding efficiency of the hemoglobin proteins in a person’s bloodstream has a great deal to do with how well the body functions, particularly under conditions of strenuous physical activity, when delivery of oxygen to the body’s muscles is the chief factor limiting the activity.
As a general rule, genes influence the phenotype by specifying the kind of proteins present in the body, which determines in large measure how that body functions.
How Mutation Alters Phenotype
A change in the identity of a single nucleotide within a gene, called a mutation, can have a profound effect if the change alters the identity of the amino acid encoded there. When a mutation of this sort occurs, the new version of the protein may fold differently, altering or destroying its function. For example, how well the hemoglobin protein performs its oxygen-binding duties depends a great deal on the precise shape that the protein assumes when it folds. A change in the identity of a single amino acid can have a drastic impact on that final shape. In particular, a change in the sixth amino acid of beta-hemoglobin from glutamic acid to valine causes the hemoglobin molecules to aggregate into stiff rods that deform blood cells into a sickle shape that can no longer carry oxygen efficiently. The resulting sickle-cell disease can be fatal.
Natural Selection for Alternative Phenotypes Leads to Evolution
Because random mutations occur in all genes occasionally, populations usually contain several versions of a gene, usually all but one of them rare. Sometimes the environment changes in such a way that one of the rare versions functions better under the new conditions. When that happens, natural selection will favor the rare allele, which will then become more common. The sickle-cell version of the beta-hemoglobin gene, rare throughout most of the world, is common in Central Africa because heterozygous individuals obtain enough functional hemoglobin from their one normal allele to get along, but are resistant to malaria, a deadly disease common there, due to their other sickle-cell allele.
Key Learning Outcome 10.5. Genes determine phenotypes by specifying the amino acid sequences, and thus the functional shapes, of the proteins that carry out cell activities. Mutations, by altering protein sequence, can change a protein's function and thus alter the phenotype in evolutionarily significant ways.