Deoxyribonucleic acid (DNA), our genetic blueprint, contains instructions that shape every aspect of our existence. While this intricate code is remarkably consistent, subtle differences exist among individuals, contributing to the rich diversity of life. These small variations make each person distinct, and single nucleotide variants (SNVs) represent one fundamental category.
What Are Single Nucleotide Variants?
A single nucleotide variant (SNV) refers to a change at a single position in the DNA sequence. DNA is composed of four nucleotide bases: adenine (A), thymine (T), cytosine (C), and guanine (G). An SNV occurs when one of these bases is replaced by another at a specific point in the genome. This distinguishes SNVs from larger genetic changes, such as insertions, deletions, or chromosomal abnormalities.
SNVs can be rare or common. A single nucleotide polymorphism (SNP) is a specific type of SNV found in at least one percent of the population. Thus, all SNPs are SNVs, but not all SNVs are SNPs. SNVs can arise in germline cells (sperm or egg cells), meaning they can be passed down through generations. They can also occur in somatic cells (non-reproductive cells), which are acquired during a person’s lifetime and are generally not hereditary.
How SNVs Arise
Single nucleotide variants primarily arise through two main mechanisms: errors during DNA replication and exposure to environmental factors. During cell division, DNA must be copied accurately for new cells to receive a complete set of genetic instructions. However, this process is not flawless.
DNA polymerases, the enzymes responsible for synthesizing new DNA strands, can occasionally incorporate an incorrect nucleotide base during copying. While the cell has robust proofreading and repair mechanisms to correct these mismatches, some errors can escape detection and become permanent changes in the DNA sequence.
External influences can also induce SNVs. Environmental factors, such as exposure to chemical mutagens or radiation, can damage DNA and lead to single base changes. For example, ultraviolet (UV) radiation from sunlight can cause DNA damage that, if not repaired, results in nucleotide substitutions. These environmentally induced SNVs are typically somatic, occurring in non-reproductive cells and not inherited.
Impact on Biological Function
Not every single nucleotide variant affects an organism’s biology; many are “silent” or neutral. Some SNVs occur in non-coding DNA regions, which do not contain instructions for making proteins. Others may be synonymous changes within a protein-coding region. A synonymous SNV alters the DNA sequence but, due to the genetic code’s redundancy, does not change the resulting protein’s amino acid sequence. While often harmless, even synonymous SNVs can sometimes influence gene expression by affecting messenger RNA (mRNA) stability or protein production efficiency.
SNVs within a gene’s coding region that lead to an amino acid change are termed non-synonymous or missense variants. The impact depends on the specific amino acid alteration and its location; some missense variants can alter a protein’s structure or function, while others have minimal effect. A more dramatic change is a nonsense or stop-gain SNV, where a nucleotide substitution introduces a premature stop signal in the mRNA sequence. This leads to a truncated, often non-functional protein, which can have significant biological consequences.
SNVs can also influence gene expression by occurring in regulatory DNA regions, such as promoters or enhancers. These regions control when and where genes are turned on or off. An SNV in these areas can alter binding sites for regulatory proteins, like transcription factors, increasing or decreasing gene product production. These changes can contribute to variations in observable traits, such as eye color or height, or affect an individual’s response to medications or environmental stimuli.
SNVs and Human Health
While many single nucleotide variants are harmless or contribute to the normal genetic diversity among people, a subset of SNVs can have significant implications for human health. Some SNVs are directly responsible for causing rare genetic conditions. Here, a single change in a specific gene leads to a clear disease phenotype, for example, by producing an altered protein that no longer functions correctly.
Beyond rare diseases, SNVs also increase an individual’s susceptibility to common and complex conditions, such as cancer, heart disease, or diabetes. These conditions often result from the combined influence of multiple SNVs and environmental factors. For instance, specific SNVs might slightly increase cancer risk, and when combined with other genetic variations or lifestyle choices, the overall risk becomes more pronounced.
The study of SNVs is increasingly relevant in personalized medicine. Analyzing an individual’s unique SNVs can provide insights into disease predisposition, even before symptoms appear. This information helps develop tailored prevention strategies, such as lifestyle modifications or early screening. Understanding an individual’s SNV profile can also guide drug selection and dosage, optimizing treatment and minimizing adverse reactions, a field known as pharmacogenomics. Genome-wide association studies (GWAS) frequently identify SNVs associated with particular diseases or traits, providing a foundation for understanding human health and disease.