The Genome, Genes, and Chromosomes

To understand the overall picture of genetic information, let us organize the relationship among the genome, genes, and chromosomes. Questions often test confusion between these levels.

Basic Knowledge

Levels of terminology:
① Genome: all the genetic information possessed by an organism. In humans, about 3 billion base pairs (3×10⁹bp).
② Gene: a specific region of DNA that specifies amino acid sequences and functions of proteins and other products. Humans have about 20,000 genes.
③ Chromosome: a structure in which DNA is wrapped around proteins called histones and condensed. Humans have 46 chromosomes (23 pairs).
Of the approximately 3 billion base pairs in the human genome, regions that code for proteins (exons) make up only 1〜2%. The rest consists of introns, noncoding RNA regions, repetitive sequences, and other regions. These were once called “junk DNA,” but they are now known to play important roles, including regulation.
Human chromosomes consist of autosomes (22 pairs) and sex chromosomes (1 pair = X・Y). XX = female, XY = male. During meiosis, sperm and eggs receive half the chromosomes (23 each), and fertilization restores the number to 46. This is the basis of sexual reproduction.

Further Study

If extended into one strand, the human genome is about 2 m long. To store it in a cell nucleus only about 10 μm in diameter, DNA is folded in multiple stages.
① DNA (2 nm in diameter)
② Wrapped around a histone octamer to form a nucleosome (10 nm in diameter)
③ Folded further into a 30 nm fiber
④ Higher-order loops and domain structures
⑤ During cell division, it becomes a highly condensed chromosome visible under a light microscope
This hierarchical folding is chemically stabilized by electrostatic interactions between the positive charges of histones (the side chains of lysine and arginine) and the negative charges of DNA (phosphate groups). When histone modification (acetylation or methylation) changes the strength of DNA binding, transcriptional activity changes. This is a basic mechanism of epigenetics and a central topic in modern medicine and developmental biology.
The Human Genome Project began in 1990 and was declared complete in 2003. Although it cost about 3 billion dollars, advances in next-generation sequencers now allow an individual's genome to be decoded for tens of thousands to 100,000 yen. It is applied to medicine (genomic medicine) and personalized drug treatment (pharmacogenomics). Together with genome-editing technologies such as CRISPR-Cas9 (2020 Nobel Prize in Chemistry), biology has entered a new era.

Points to Note

① Do not confuse the hierarchy of genome (all information) >>> gene (an individual region) >>> base pair (the smallest unit). ② Chromosome and gene are different concepts. A single chromosome contains many genes. ③ Humans have 46 chromosomes (23 pairs). Children inherit 23 chromosomes in their gametes. ④ Genome size and gene number are not proportional because the amount of repetitive sequence differs greatly among species. For example, the lily genome is 30 times larger than the human genome.

Practice

1. Approximately how many base pairs are in the human genome?
2. How many chromosomes do humans have? Give the numbers of autosomes and sex chromosomes.
3. What protein does DNA wrap around to form chromosome structures?