Deoxyribonucleic acid (DNA) is the instruction manual for all living things, written in an alphabet of four chemical bases: adenine (A), cytosine (C), guanine (G), and thymine (T). The order of these bases forms a DNA sequence that dictates genetic information. While genes are long stretches of DNA that code for proteins, much of the genome’s function is controlled by short DNA sequences. These smaller segments, a few to several hundred base pairs long, do not code for proteins but play other regulatory roles.
Biological Roles of Short DNA Sequences
The primary function of many short DNA sequences is regulating gene expression, the process of turning genes “on” or “off.” These sequences act as binding sites for proteins called transcription factors. When attached to the DNA, these proteins can either help or hinder the cellular machinery responsible for reading a gene, providing instructions on how, when, and to what degree a gene should be read.
A common type of regulatory sequence is the promoter, located near the beginning of a gene. The promoter acts as a “start” signal, indicating where the transcription of DNA into RNA should begin. Specialized proteins recognize these sequences to initiate gene expression. Without a promoter, the cell’s machinery cannot read the genetic code, and the gene remains silent.
Other short DNA sequences, known as enhancers, increase gene activity. Enhancers can be located thousands of base pairs away from the gene they regulate. When activator proteins bind to an enhancer, the DNA can loop, bringing the enhancer into close contact with the promoter region. This interaction stimulates transcription of the gene. Silencer sequences have the opposite effect, binding repressor proteins that prevent a gene from being expressed.
Terminator sequences, found at the end of a gene, signal the completion of transcription. These sequences cause the transcribing machinery to detach from the DNA strand, ensuring the resulting RNA molecule is the correct length. This network of promoters, enhancers, silencers, and terminators allows cells to control the expression of thousands of genes. This control is particularly important during an organism’s development.
Repetitive Short DNA Sequences
A distinct category of short DNA sequences consists of segments repeated in a continuous block, known as Short Tandem Repeats (STRs). An STR is a sequence of two to six base pairs, such as “GATA,” repeated multiple times at a specific location (locus) in the genome. For example, one person might have the “GATA” sequence repeated 10 times, while another has it repeated 15 times at the same locus.
The defining characteristic of STRs is their high variability among individuals. While the DNA sequences flanking an STR locus are stable, the number of repeats within the STR differs from person to person. This variation arises from errors during DNA replication, where the cellular machinery may slip and add or remove a repeat unit.
This variability in repeat numbers across numerous STR loci creates a unique genetic profile for each person. Humans inherit one copy of their DNA from each parent, resulting in two versions (alleles) of each STR locus. The number of repeats on the maternal and paternal chromosomes may be the same or different. This combination of repeat numbers at multiple locations is what makes these sequences useful for identification.
Applications in Forensics and Paternity
The high variability of STRs forms the basis of modern DNA profiling, or “DNA fingerprinting.” Forensic scientists analyze a standardized set of STR loci to generate a unique profile for an individual. The process begins by collecting a biological sample, like blood or saliva, from which DNA is extracted. Specific STR regions are then targeted for analysis.
Scientists use the Polymerase Chain Reaction (PCR) to make millions of copies of the specific STR loci. This amplification generates enough DNA for analysis, even from a small initial sample. After amplification, the STR fragments are separated by size using capillary electrophoresis. Since a fragment’s length is determined by its number of repeats, this technique measures how many repeats are present at each locus for both the maternal and paternal chromosomes.
The result is a series of numbers representing the repeat counts at each STR locus. For example, a profile at one locus might be “11, 14,” meaning 11 repeats were inherited from one parent and 14 from the other. By analyzing a standard set of 20 core STR loci, like those in the Combined DNA Index System (CODIS), the probability of two unrelated individuals sharing the same profile is infinitesimally small. This makes STR analysis a powerful tool for matching a suspect’s DNA to evidence from a crime scene.
This methodology is also applied to paternity testing. A child inherits half of their DNA from each parent, so their STR profile is compared to the alleged father’s. For each STR locus, the child must have one allele that matches the mother and one that matches the father. A consistent match across multiple loci provides evidence of a biological relationship.
Uses in Medicine and Biotechnology
Short DNA sequences are also tools in medicine and biotechnology. In diagnostics, synthetic short sequences called DNA probes are designed to bind to specific genetic sequences. These probes are labeled with a fluorescent or radioactive tag, allowing scientists to visually confirm the presence of a DNA sequence associated with a genetic disorder or infectious agent. This enables the detection of disease markers in a patient’s sample.
The Polymerase Chain Reaction (PCR) relies on short DNA sequences called primers. Primers are engineered to match the DNA flanking a target region. In a lab, these primers guide the DNA polymerase enzyme to the segment of the genome to be copied, allowing for the amplification of that sequence. This technique is used in medical diagnostics, genetic research, and the forensic analysis of STRs.
Gene-editing technologies like CRISPR-Cas9 use short RNA sequences, which are transcribed from DNA templates. A short “guide RNA” is designed to match a target sequence in the genome. This guide RNA directs the Cas9 enzyme, a type of molecular scissors, to that location to make a cut in the DNA. This action allows scientists to disable a gene, correct a harmful mutation, or insert new genetic material to treat genetic diseases.