Chromosomes are microscopic units containing organized genetic information, eukaryotic chromosomes are located in the nuclei of diploid and haploid cells (e.g., human somatic and sex cells). Prokaryotic chromosomes are also present in one-cell non-nucleated (unicellular microorganisms ) prokaryotic cells (e.g., bacteria ). The sum-total of genetic information contained in different chromosomes of a given individual or species are generically referred to as the genome.
In humans, eukaryotic chromosomes are structurally made of roughly equal amounts of proteins and DNA . Each chromosome contains a double-strand DNA molecule, arranged as a double helix, and tightly coiled and neatly packed by a family of proteins called histones. DNA strands are comprised of linked nucleotides. Each nucleotide has a sugar (deoxyribose), a nitrogenous base, plus one to three phosphate groups. Each nucleotide is linked to adjacent nucleotides in the same DNA strand by phosphodiester bonds. Phosphodiester is another sugar, made of sugar-phosphate. Nucleotides of one DNA strand link to their complementary nucleotide on the opposite DNA strand by hydrogen bonds, thus forming a pair of nucleotides, known as a base pair, or nucleotide base.
Chromosomes contain the genes, or segments of DNA, that encode for proteins of an individual. Genes contain up to thousands of sequences of these base pairs. What distinguishes one gene from another is the sequence of nucleotides that code for the synthesis of a specific protein or portion of a protein. Some proteins are necessary for the structure of cells and tissues. Others, like enzymes , a class of active (catalyst) proteins, promote essential biochemical reactions, such as digestion, energy generation for cellular activity, or metabolism of toxic compounds. Some genes produce several slightly different versions of a given protein through a process of alternate transcription of bases pairs segments known as codons. When a chromosome is structurally faulty, or if a cell contains an abnormal number of chromosomes, the types and amounts of the proteins encoded by the genes are altered. Changes to proteins often result in serious mental and physical defects and disease.
Within the chromosomes, the DNA is tightly coiled around proteins (e.g., histones) allowing huge DNA molecules to occupy a small space within the nucleus of the cell. When a cell is not dividing, the chromosomes are invisible within the cell's nucleus. Just prior to cell division, the chromosomes uncoil and begin to replicate. As they uncoil, the individual chromosomes take on a distinctive appearance that allows physicians and scientists to classify the chromosomes by size and shape.
Numbers of autosomal chromosomes differ in cells of different species; but are usually the same in every cell of a given species. Sex determination cells (mature ovum and sperm) are an exception, where the number of chromosomes is halved. Chromosomes also differ in size. For instance, the smallest human chromosome, the sex chromosome Y, contains 50 million base pairs (bp), whereas the largest one, chromosome 1, contains 250 million base pairs. All 3 billion base pairs in the human genome are stored in 46 chromosomes. Human genetic information is therefore stored in 23 pairs of chromosomes (totaling 46), 23 inherited from the mother, and 23 from the father. Two of these chromosomes are sex chromosomes (chromosomes X and Y). The remaining 44 are autosomes (in 22 autosomal pairs), meaning that they are not sex chromosomes and are present in all somatic cells (i.e., any other body cell that is not a germinal cell for spermatozoa in males or an ovum in females). Sex chromosomes specify the offspring gender: normal females have two X chromosomes and normal males have one X and one Y chromosome. These chromosomes can be studied by constructing a karyotype, or organized depiction, of the chromosomes.
Each set of 23 chromosomes constitutes one allele, containing gene copies inherited from one of the progenitors. The other allele is complementary or homologous, meaning that they contain copies of the same genes and on the same positions, but originated from the other progenitor. As an example, every normal child inherits one set of copies of gene BRCA1, located on chromosome 13, from the mother and another set of BRCA1 from the father, located on the other allelic chromosome 13. Allele is a Greek-derived word that means "one of a pair," or any one of a series of genes having the same locus (position) on homologous chromosomes.
The first chromosome observations were made under light microscopes, revealing rod-shaped structures in varied sizes and conformations, commonly J- or V-shaped in eukaryotic cells and ring-shaped in bacteria. Staining reveals a pattern of light and dark bands. Today, those bands are known to correspond to regional variations in the amounts of the two nucleotide base pairs: Adenine-Thymine (A-T or T-A) in contrast with amounts of Guanine-Cytosine (G-C or C-G).
In humans, two types of cell division exist. In mitosis, cells divide to produce two identical daughter cells. Each daughter cell has exactly the same number of chromosomes. This preservation of chromosome number is accomplished through the replication of the entire set of chromosomes just prior to mitosis.
Two kinds of chromosome number defects can occur in humans: aneuploidy, an abnormal number of chromosomes, and polyploidy, more than two complete sets of chromosomes. Most alterations in chromosome number occur during meiosis. During normal meiosis, chromosomes are distributed evenly among the four daughter cells. Sometimes, however, an uneven number of chromosomes are distributed to the daughter cells.
Genetic abnormalities and diseases occur if chromosomes or portions of chromosomes are missing, duplicated or broken. Abnormalities and diseases may also occur if a specific gene is transferred from one chromosome to another (translocation), or there is a duplication or inversion of a segment of a chromosome. Down syndrome, for instance, is caused by trisomy in chromosome 21, the presence of a third copy of chromosome 21. Some structural chromosomal abnormalities have been implicated in certain cancers. For example, myelogenous leukemia is a cancer of the white blood cells. Researchers have found that the cancerous cells contain a translocation of chromosome 22, in which a broken segment switches places with the tip of chromosome 9.
In non-dividing cells, it is not possible to distinguish morphological details of individual chromosomes, because they remain elongated and entangled to each other. However, when a cell is dividing, i.e., undergoing mitosis, chromosomes become highly condensed and each individual chromosome occupies a well-defined spatial location.
Karyotype analysis was the first genetic screening utilized by geneticists to assess inherited abnormalities, like additional copies of a chromosome or a missing copy, as well as DNA content and gender of the individual. With the development of new molecular screening techniques and the growing number of identified individual genes, detection of other more subtle chromosomal mutations is now possible (e.g., determinations of gene mutations, levels of gene expression, etc.). Such data allow scientists to better understand disease causation and to develop new therapies and medicines for those diseases.
In mitosis, cells divide to produce two identical daughter cells. Each daughter cell has exactly the same number of chromosomes. This preservation of chromosome number is accomplished through the replication of the entire set of chromosomes just prior to mitosis.
Sex cells, such as eggs and sperm, undergo a different type of cell division called meiosis. Because sex cells each contribute half of a zygote's genetic material, sex cells must carry only half the full complement of chromosomes. This reduction in the number of chromosomes within sex cells is accomplished during two rounds of cell division, called meiosis I and meiosis II. Prior to meiosis I, the chromosomes replicate and chromosome pairs are distributed to daughter cells. During meiosis II, however, these daughter cells divide without a prior replication of chromosomes. Mistakes can occur during either meiosis I and meiosis II. Chromosome pairs can be separated during meiosis I, for instance, or fail to separate during meiosis II.
Meiosis produces four daughter cells, each with half of the normal number of chromosomes. These sex cells are called haploid cells (meaning half the number). Non-sex cells in humans are called diploid (meaning double the number) since they contain the full number of normal chromosomes.
Most alterations in chromosome number occur during meiosis. When an egg or sperm that has undergone faulty meiosis and has an abnormal number of chromosomes unites with a normal egg or sperm during conception, the zygote formed will have an abnormal number of chromosomes. If the zygote survives and develops into a fetus, the chromosomal abnormality is transmitted to all of its cells. The child that is born will have symptoms related to the presence of an extra chromosome or absence of a chromosome.
See also Cell cycle (eukaryotic), genetic regulation of; Cell cycle (prokaryotic), genetic regulation of; Chromosomes, prokaryotic; DNA (Deoxyribonucleic acid); Enzymes; Genetic regulation of eukaryotic cells; Genetic regulation of prokaryotic cells; Molecular biology and molecular genetics