DNA and its Functions

The Significance of Mutations in Evolution and Disease

Mutations are permanent alterations in the DNA sequence that differ from the sequence found in most people. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome that includes multiple genes. Gene mutations can be classified in two major ways: hereditary mutations are inherited from a parent and are present throughout a person’s life in virtually every cell in the body. These mutations are also called germline mutations because they are present in the parent’s egg or sperm cells, which are the reproductive cells. Acquired (or somatic) mutations occur at some time during a person’s life and are present only in certain cells, not in every cell in the body. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed to the next generation. Genetic changes that are described as de novo (new) mutations can be either hereditary or somatic. In addition to small-scale mutations, such as those affecting a single gene, larger-scale mutations can involve the addition or loss of entire chromosomes or sets of chromosomes.

Complementary Base Pairing: A Key Principle in DNA Structure and Sequencing

An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell. The double helix model shows DNA as two parallel strands of intertwining molecules. The sugar and phosphate lie on the outside of the helix, forming the backbone of the DNA. The nitrogenous bases are stacked in the interior, like the steps of a staircase, in pairs; the bases form hydrogen bonds with each other, which is called base pairing. Adenine pairs with thymine, and guanine pairs with cytosine. DNA can replicate itself by separating into individual strands, each of which becomes a template for the formation of a complementary strand according to the rules of base pairing.

Gene Expression: Transcription and Translation Processes

Gene expression is the process by which the instructions in our DNA are converted into a functional product, such as a protein. This process can be divided into two main steps: transcription and translation. During transcription, the DNA sequence of a gene is copied into RNA (specifically, messenger RNA or mRNA) by the enzyme RNA polymerase. This mRNA then carries the genetic information needed for protein synthesis from the nucleus to the cytoplasm, where the cell’s ribosomes are located. In translation, the mRNA is used as a template to assemble amino acids into a polypeptide chain that will fold into a functional protein. The ribosome reads the sequence of mRNA bases in groups of three, known as codons, and matches them with the corresponding amino acids, which are brought to the ribosome by another type of RNA called transfer RNA (tRNA). The sequence of codons determines the sequence of amino acids in the protein.

Techniques and Advancements in DNA Sequencing

Since the initial discovery of the DNA double helix, there have been major advances in DNA sequencing technologies. The first DNA sequences were obtained in the early 1970s by academic researchers using laborious methods based on two-dimensional chromatography. Following the development of the Sanger method in 1977, DNA sequencing has become easier and more reliable, and the Sanger method is still widely used, especially for small-scale projects. The advent of next-generation sequencing (NGS) technologies has revolutionized the field, making it possible to sequence large amounts of DNA quickly and at a lower cost. NGS technologies work by sequencing millions of small fragments of DNA in parallel, then using computer algorithms to assemble these fragments into a complete sequence. These advancements have had a profound impact on the field of genomics, enabling researchers to sequence whole genomes and perform a wide variety of genetic analyses.

The Human Genome Project and the Evolution of DNA Sequencing

The Human Genome Project (HGP) was an international research effort to sequence and map all the genes — together known as the genome — of members of our species, Homo sapiens. Completed in April 2003, the HGP gave us the ability, for the first time, to read nature’s complete genetic blueprint for building a human being. This project was a landmark study in the field of genomics and has led to significant advances in our understanding of genetics and medicine. The HGP also spurred the development of new sequencing technologies and accelerated the pace of genome research. The cost of sequencing a human genome has dropped dramatically since the completion of the HGP, from approximately $1 billion to just a few thousand dollars, making it a routine tool in biomedical research. The HGP has also paved the way for personalized medicine, where medical treatment can be tailored to the individual genetic makeup of each patient.