3.8: The origins of polymorphisms

So what produces the genomic variations found in different individuals in a population? Are these processes continuing to produce genotypic and phenotypic variations or have they ended? First, as we have alluded to, and will return to again and again, the sequence of letters in an organism’s genome corresponds to the sequence of in DNA molecules. A DNA molecule in water (and over ~70% of a typical cell is water) is thermodynamically unstable and can undergo various types of reactions, such as deamination, depurination, and depyrimidination that can, if not repaired, lead to changes in the sequence of characters within the molecule (discussed later).^[116] In addition, we are continually bombarded by radiation that can damage DNA.^[117] Mutagenic radiation, that is, the types of radiation capable of damaging a DNA molecule, arises from various sources, including cosmic rays that originate from outside of the solar system, UV light from the sun, the decay of naturally occurring radioactive isotopes found in rocks and soil (e.g. radon), and the ingestion of naturally occurring isotopes, such as potassium-40. When a DNA molecule absorbs such radiation it can lead to chemical changes in its DNA, that is, mutations. Many but not all of these changes can be identified and repaired by cellular repair systems (to be discussed later).

The second, and major source of change to the genome involves the process of DNA replication. DNA replication happens every time a cell divides. While remarkably accurate it is not perfect; copying can lead to mistakes. In humans, it appears that DNA replication creates one error for every ~1,000,000,000 (10⁹) characters copied. Cells have systems that can correct ~99% of these errors, leading to an overall error rate during replication of about 1 in 10¹⁰ bases replicated. Since a single human cell contains ~6,400,000,000 bases of DNA sequence, that means that generally less than one new mutation is introduced per cell division cycle. Given the number of generations (cell division cycles) from fertilized egg to sexually active adult, that results in about ~100-200 new mutations (changes) added to an individual’s genome per generation.^[118] These mutations can have a wide range of effects, complicated by the fact that essentially all of the various aspects of an organism’s phenotype are determined by the action of hundreds to thousands of genes working in a complex network that is influence by intrinsic and environmental factors. When a mutation leads to a change in a gene, it the new version is known as an allele of the gene. When a mutation changes the DNA’s sequence, whether or not it is part of a gene, it creates what is known as a sequence polymorphism or simply a polymorphism, a different DNA sequence. Once an allele or polymorphism has been generated, it is as stable as the original molecule - it can be inherited from a parent and passed on to an offspring. Through the various processes associated with reproduction, which we will consider in detail later on, each organism carries its own distinctive set of alleles and its own unique set of polymorphisms. Taken together these genotypic differences, that is, differences in alleles and polymorphisms, produce different phenotypes. The DNA tests used to determine paternity and forensic identity work because they use the unique polymorphisms and alleles present within an individual’s genome as a type of bar code for that person.

Two points are worth noting about genomic changes or mutations. First, whether produced by mistakes in replication or chemical or photochemical reactions, it appears that these changes occur randomly within the genome. With a few notable and highly specific exceptions, for example, in the immune system, there are no known mechanisms by which the environment (or the organism) can influence where a mutation will occur. The second point is that a mutation may or may not influence an organism’s phenotype. The effects of a mutation will depend on a number of factors, including exactly where the mutation is in the genome, its specific nature, the role of the mutated gene, the rest of the genome–known as the genetic background–and the environment in which the organism finds itself. We will consider the factors that influence gene and genome dynamics when we return to the behavior of DNA in cells.

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