DNA, our genetic blueprint, contains instructions organized into genes, which dictate the production of specific proteins or functional RNA molecules. Sometimes, a section of this DNA gets copied and inserted right next to the original segment, a change known as a tandem duplication. These genetic alterations are common across various life forms and can profoundly affect an organism’s traits and health.
How Tandem Duplications Arise
Tandem duplications often result from accidental events during cellular processes like cell division or DNA replication. One common way they form is through unequal crossing over during meiosis, the cell division that produces reproductive cells. During this process, homologous chromosomes, inherited from each parent, align and exchange genetic material. If these chromosomes misalign due to repetitive DNA sequences, the exchange can be uneven, leading to one chromosome gaining an extra segment (a duplication) and the other losing it (a deletion).
Another mechanism is replication slippage, an error that occurs during DNA replication. DNA polymerase, the enzyme synthesizing new DNA strands, can “slip” when it encounters repetitive sequences in the DNA template. This slippage causes the newly synthesized strand to detach and misalign with the template strand. When DNA polymerase resumes replication, it might re-copy a segment, resulting in an insertion or expansion of the repetitive sequence, thus creating a tandem duplication.
Role in Evolution and Adaptation
Tandem duplications provide raw material for evolutionary change, allowing new genes and functions to develop. One way this occurs is through an increase in gene dosage, where an organism has more copies of a gene. Multiple copies can lead to increased protein production, which can be advantageous in certain environments or conditions. For example, a duplicated gene might produce more of an enzyme needed to break down a new food source, offering a survival advantage.
Beyond increasing protein levels, tandem duplications can also create novel genes. When a gene is duplicated, one copy is freed from immediate selective pressure to maintain its original function, as the other copy performs that role. This allows the duplicated gene to accumulate mutations and evolve new functions without harming the organism. Examples include the globin gene family, which originated from ancient duplications and diversified to carry oxygen in different tissues or developmental stages. Olfactory receptor genes have also expanded through tandem duplication, allowing organisms to detect a wide range of smells. These new genes or modified gene products can provide an adaptive advantage, enabling organisms to thrive in changing environments and contributing to life’s diversity.
Association with Human Disease
While tandem duplications can drive evolution, they also contribute to human diseases. An imbalance in gene dosage, with too many gene copies, can disrupt normal cellular processes. This excess protein production can be harmful or interfere with other cellular functions, leading to disease. For instance, Charcot-Marie-Tooth disease type 1A (CMT1A), a neurological disorder affecting peripheral nerves, is caused by a 1.5-million-base-pair tandem duplication on chromosome 17 that includes the PMP22 gene. This duplication results in three copies of the PMP22 gene instead of two, leading to overproduction of the PMP22 protein, which disrupts the myelin sheath insulating nerves.
Tandem duplications can also occur within a gene, altering its sequence and leading to a non-functional or aberrantly functional protein. These disruptions can have severe consequences for cellular processes. Tandem duplications are also implicated in certain cancers. For example, in some breast and ovarian cancers, BRCA1 gene inactivation is associated with specific patterns of tandem duplications. These duplications can increase the copy number of oncogenes (genes that promote cell growth) or disrupt tumor suppressor genes (which regulate cell division), contributing to uncontrolled cell growth and tumor development.