Methods & Tools of Cell Biology

DNA sequencing

/ DEE-en-ay SEE-kwen-sing /

DNA stores its information as a long string of just four chemical 'letters' — A, T, G, and C — much like a book written in a four-letter alphabet. Reading nothing but a smear of DNA tells you almost nothing; the meaning lies in the exact order of the letters. DNA sequencing is the technology that reads out that order, letter by letter, turning a physical molecule into a text you can store, search, and compare.

Modern sequencing reads DNA by detecting each base as it is added or as the molecule is processed. In one widely used approach, the machine builds a new strand opposite the DNA being read and flashes a signal — often a burst of light of a particular colour — each time a specific letter is incorporated, recording the sequence as it goes. Today's machines run millions of these reads in parallel, so a whole human genome of three billion letters can be read in a day or two. The short reads are then stitched together by computer into the full sequence.

DNA sequencing reshaped biology and medicine: it let us read entire genomes, trace evolutionary relationships, pinpoint disease-causing mutations, identify unknown microbes, and tailor treatments to a patient's own DNA. Its honest limits matter. Sequencing tells you the order of letters — what the recipe says — but not on its own which genes are switched on, how the cell uses them, or what an unfamiliar sequence actually does. And reads contain occasional errors, so important findings are confirmed by reading the same region multiple times.

To diagnose a baby's unexplained illness, doctors sequence the child's genome and find a single changed letter in one gene — a tiny typo in three billion that explains the disease and guides treatment.

Sequencing reads the order of the four DNA letters — the text, not yet its meaning.

Knowing the sequence is not the same as knowing the function: sequencing reads what the letters are, but tells you nothing on its own about which genes are active or what an unknown stretch of DNA actually does.

Also called
genome sequencingDNA 序列测定基因組定序