The unique genetic blueprint within each of our cells is often imagined as a fixed and constant script, but this view is incomplete. While the sequence of our DNA is a large part of what makes us who we are, the quantity of that DNA can also differ from person to person. This article will explore the concept of DNA copy number, explain how and why it varies among individuals, and discuss the implications these variations have for human health, diversity, and evolution.
Our Genetic Code: The Basics of DNA and Genes
To understand how the quantity of DNA can vary, it is helpful to grasp a few fundamentals of genetics. Deoxyribonucleic acid, or DNA, is a molecule that holds the detailed instructions for building and maintaining an organism. These instructions are encoded in its structure, a long chain of smaller units called nucleotides. For efficiency, this vast amount of information is organized into structures called chromosomes.
Inside our cells, the long strands of DNA are tightly coiled and packaged into structures called chromosomes. Think of the entire genetic code as an extensive instruction manual; the chromosomes are the individual volumes of this manual. Humans have 23 pairs of chromosomes in each cell, for a total of 46.
We receive one set of 23 chromosomes from our mother and a corresponding set from our father. This means that for most of our genome, we have two copies of each chromosome and, by extension, two copies of the genes they contain. Genes are specific segments of DNA that provide the instructions for a single function, such as building a particular protein.
This two-copy framework is a general rule, but it is not absolute. The mechanisms that copy and transmit DNA from one generation to the next can introduce changes. These changes can alter not just the sequence of the genetic code, but also the number of times a specific part of that code is present.
Defining DNA Copy Number and Its Variations
DNA copy number refers to the number of copies of a particular segment of DNA present in the genome of an individual. For much of the human genome, this number is two, reflecting the inheritance of one chromosome from each parent. However, certain regions of our DNA can be present in more or fewer than two copies.
These differences are known as Copy Number Variations, or CNVs. A CNV is a segment of DNA, typically larger than 50 nucleotide bases, that is found in a variable number of copies when comparing one individual’s genome to another’s. Some people might have one copy of a specific genetic segment, while others have two, three, or even more.
It is helpful to distinguish CNVs from another well-known type of genetic variation, the Single Nucleotide Polymorphism (SNP). A SNP is a change in a single “letter” of the DNA code. In contrast, CNVs involve much larger chunks of DNA, ranging from thousands to millions of bases. Because they cover such large stretches, CNVs account for a greater total amount of genetic difference between any two people than SNPs do.
The Origins of Copy Number Differences
The variations in the number of copies of a DNA segment arise from errors that can occur when cells divide and replicate their genetic material. Over evolutionary time and across large populations, they have generated a substantial amount of structural diversity in the human genome. The two primary mechanisms that create CNVs are deletions and duplications.
A deletion occurs when a segment of a chromosome is lost during DNA replication or repair. As a result, an individual might inherit a chromosome that is missing a particular piece of genetic information. This leads to having fewer copies of that segment and the genes within it compared to the general population.
Conversely, a duplication happens when a segment of a chromosome is repeated, resulting in extra copies of that specific DNA sequence. These duplication and deletion events often happen during meiosis, the specialized cell division process that creates sperm and egg cells. Errors in the alignment and recombination of chromosomes can lead to one reproductive cell receiving a chromosome with a duplicated segment and another receiving one with a deleted segment.
Why Copy Number Variations Matter
The impact of having more or fewer copies of a DNA segment ranges from being completely harmless to having consequences for health and development. Many CNVs are common in the human population and are simply part of the normal spectrum of genetic diversity. They can influence physical traits, metabolic processes, and how we interact with our environment. For instance, the number of copies of the AMY1 gene, which produces an enzyme for digesting starch, is thought to be related to historical dietary habits.
However, some CNVs can disrupt the genome in ways that lead to disease. Losing a copy of a gene that performs a necessary function can cause a genetic disorder. Conversely, having extra copies of certain genes can lead to an overproduction of specific proteins, which can also be detrimental. CNVs have been linked to a wide range of conditions, including:
- Developmental delays
- Autism spectrum disorders
- Schizophrenia
- Autoimmune diseases
- Susceptibility to certain types of cancer
From an evolutionary perspective, CNVs are an engine of change. Gene duplication, in particular, provides raw material for the evolution of new functions. When an extra copy of a gene is created, the original copy can continue to perform its established role, while the new copy is free to accumulate mutations. Over generations, this duplicated gene can diverge and potentially take on a completely new function, contributing to the adaptation and complexity of a species.