Polymorphism (biology)

In genetics, polymorphism (Greek πολυμορφισμός polymorphismos 'polymorphism') refers to the occurrence of several gene variants within a population. The different variants of a particular gene at the same gene locus are also called alleles.

Genetic variations do not always have to result in distinguishable gene products and can be restricted to the genotype. A variation in the base sequence of DNA alone, a sequence variation, is referred to in molecular biology as a polymorphism if there are several variants that can be converted into one another by mutation. Sequence variations within the coding DNA segments, however, usually have an effect on the gene product, and different proteins are then formed according to the variant templates.

A different gene product can lead to trait variations in the appearance of organisms. If several clearly distinguishable phenotypes occur as a result of variant genes, this is referred to in biology as polymorphism. By definition, the rarer gene variant must have a frequency of occurrence (allele frequency) of more than one percent within a population; otherwise, this is also referred to as a sequence variation or a mutation.

An enzyme or protein polymorphism exists when a polymorphism of the genetic information - in the genome - also means a distinguishability of the respective gene product, and beyond the transcription into RNA - in the transcriptome - by translation then also one of the synthesized protein - in the proteome - causes, for example, a certain enzyme.

Synonymous with polymorphism can also be used polymorphism, heteromorphism and discontinuous polymorphism.

Sequence Variations

Three types of sequence variation can be distinguished:

• Single Nucleotide Polymorphisms (SNP)
• small insertion and deletion polymorphisms (usually <50 nucleotides), also called INDELs.
• Structural variants (or copy number variants, CNVs).

The most common sequence variations are the single nucleotide polymorphisms (SNP), which are based on the exchange of a nucleotide in the DNA molecule. It is assumed that there is one SNP in 200 to 1000 base pairs in the human genome. If the SNP is located in the coding region of a gene sequence, this can result in the exchange of an amino acid in the resulting protein. However, since several different base triplets often stand for the same amino acid in the genetic code, not every base exchange in the DNA necessarily results in an amino acid exchange in the protein.

An insertion or - the opposite - a deletion is the insertion or loss of at least one nucleotide. This can lead (if both alleles are affected) to no activity being detectable for the gene product (an enzyme). Smaller insertions and deletions (<50 nucleotides) are referred to as INDELs.

CNVs (gene duplications, multiplications or deletions) can eventually affect the entire gene. This can lead, for example, to a significant increase in the metabolic capacity of the affected gene product.

Effects of sequence variations

It is repeatedly observed that in a group of people living under comparable conditions and jointly exposed to certain environmental influences, only some individuals are affected by health effects as a consequence of these environmental influences: For example, in rare cases, chain smokers live to a comparatively old age, whereas occasional smokers with a corresponding genetic predisposition may die early from lung cancer. Enzymes that can break down such foreign substances always play an important role in dealing with the environment and the foreign substances absorbed from it. Sequence variations can lead to significant differences in the degradation of foreign substances in the bodies of different individuals, as shown by studies of accidents and drug side effects. However, these findings have no practical utility applications to date. Considerable ethnic differences in the occurrence of sequence variations have also been observed, the reasons for which are still unclear.

The increasing accuracy with which sequence variations can be detected using genetic tests raises growing ethical problems: for example, should individuals with known risk factors be excluded from certain professions? What consequences will knowledge of a particular sequence variation have for the purchase of life insurance? On the other hand, improved information about risks (for example, an increased risk of heart attack with certain polymorphisms) could give an affected person reason to try to actively counteract a possible disease - for example, through a healthy diet, exercise and targeted preventive care - and thus possibly improve their own quality of life.