particular point in a gene. Point mutations can be changes that convert one type of nucleotide to another (a C to a T, for instance), or cause the deletion or addition of a single nucleotide. While the rate of mutation is slow, over long periods (millions of years) most possible sequence changes will have occurred several times in a population, and so natural selection is likely to have acted on most genes in almost every modern population.
Some point mutations can change the amino acid sequence of the resulting protein, altering its properties. For instance, a digestive enzyme's attraction for its substrate (the food molecule it breaks down) may be altered to allow the organism to digest new foods, or prevent it from digesting old ones. The sickle form of hemoglobin arose because of a point mutation that changed a single amino acid in hemoglobin. The result was a molecule that bound oxygen less tightly under certain conditions, conferring resistance to malaria, but also causing sickle cell disease, a type of hemoglobinopathy.
Other point mutations may leave the protein unchanged, but alter the conditions under which it is expressed. Genes are expressed (that is, are "read" to cause protein production) when transcription factors bind to a region of the gene known as the promoter. Promoters interact with other DNA regions, called enhancers, which are often a long distance from the gene along the chromosome, but are nonetheless close to it because of folding of the DNA. Mutations in either the promoter or enhancer region can have profound effects on the sensitivity of expression to hormones, temperature changes, and other regulatory influences. For instance, a human gene coding for one form of an enzyme called pancreatic elastase appears to have been silenced by an evolutionarily recent enhancer mutation.
Not all DNA sequence changes will lead to changes in the encoded protein or in the way that it is expressed. For many amino acids, there are several DNA "synonyms" that all code for the same amino acid. GGG, GGC, GGA, and GGT all code for the amino acid proline, for example. This is known as the degeneracy of the genetic code. Also, mutations that code for chemically similar amino acids may have no significant effect on protein function. For instance, leucine (AAT) and isoleucine (TAT) are both small, nonpolar amino acids often found on the interior of proteins. Mutations that exchange one for the other may have little effect on protein structure or function.
Genes in eukaryotes also contain noncoding regions, called introns. Mutations in these regions often have no effect, since their sequences do not code for part of the finished protein. Changes to the ends of introns and certain internal sequences may have an effect, however, since these control the removal of the intron sequence from the RNA copy after transcription. A mutation here can prevent intron removal, altering the finished protein. One form of the hemoglobin disease beta-thalassemia is due to an intron mutation.
transcription factors proteins that increase the rate of gene transcription eukaryotes organisms with cells possessing a nucleus
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