Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Chromosomes, eukaryotic

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thousands of sequences of these base pairs. What distin-

guishes one genefrom 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 (cat-

alyst) proteins, promote essential biochemical reactions, such

as digestion, energy generation for cellular activity, or metab-

olism of toxic compounds. Some genes produce several

slightly different versions of a given protein through a

process of alternate transcriptionof 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 nucleusof 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, chromo-

some 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 chro-

mosomes (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, con-

taining 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 posi-

tions, 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 chro-

mosome 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 eukary-

otic cells and ring-shaped in bacteria. Staining reveals a pattern

of light and dark bands. Today, those bands are known to corre-

spond to regional variations in the amounts of the two

nucleotide base pairs: Adenine-Thymine (A-T or T-A) in con-

trast 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 daugh-

ter cells.

Genetic abnormalities and diseases occur if chromo-

somes or portions of chromosomes are missing, duplicated or

broken. Abnormalities and diseases may also occur if a spe-

cific gene is transferred from one chromosome to another

(translocation), or there is a duplication or inversion of a seg-

ment 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 abnor-

malities 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 uti-

lized 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 devel-

opment of new molecular screening techniques and the grow-

ing number of identified individual genes, detection of other

more subtle chromosomal mutationsis 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 daugh-

ter 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 chro-

mosomes 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

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