Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Gene

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gene is an individual element of an organism’s genome and

determines a trait or characteristic by regulating biochemical

structure or metabolic process.

Genes are segments of nucleic acid, consisting of a spe-

cific sequence and number of the chemical units of nucleic

acids, the nucleotides. In most organisms, the nucleic acid is

DNA (deoxyribonucleic acid), although in retroviruses, the

genetic material is composed of ribonucleic acid(RNA). Some

genes in a cell are active more or less all the time, which

means they are continuously transcribed and provide a con-

stant supply of their protein product. These “housekeeping”

genes are always needed for basic cellular reactions. Others

may be rendered active or inactive depending on the needs and

functions of the organism under particular conditions. The sig-

nal that masks or unmasks a gene can come from outside the

cell, for example, from a steroid hormone or a nutrient, or it

can come from within the cell itself because of the activity of

other genes. In both cases, regulatory substances can bind to

the specific DNA sequences of the target genes to control the

synthesis of transcripts.

In a paper published in 1865, Gregor Mendel

(1823–1884), advanced a theory of inheritance dependent on

material elements that segregate independently from each

other in sex cells. Before Mendel’s findings, inherited traits

were thought to be passed on through a blending of the mother

and father’s characteristics, much like a blending of two liq-

uids. The term “gene” was coined later by the Danish botanist

Wilhelm Johannsen (1857–1927), to replace the variety of

terms used up until then to describe hereditary factors. His

definition of the gene led him to distinguish between genotype

(an organism’s genetic makeup) and phenotype(an organ-

ism’s appearance). Before the chemical and physical nature of

genes were discovered they were defined on the basis of phe-

notypic expression and algebraic symbols were used to record

their distribution and segregation. Because sexually reproduc-

ing, eukaryotic organisms possess two copies of an inherited

factor (or gene), one acquired from each parent, the genotype

of an individual for a particular trait is expressed by a pair of

letters or symbols. Each of the alternative forms of a gene is

also known as alleles. Dominant and recessive alleles are

denoted by the use of higher and lower case letters. It can be

predicted mathematically, for example, that a single allele pair

will always segregate to give a genotype ratio 1AA:2Aa:1aa,

and the phenotype ratio 2A:1aa (where A represents both AA

and Aa since these cannot be distinguished phenotypically if

dominance is complete).

The molecular structure and activity of genes can be

modified by mutationsand the smallest mutational unit is now

known to be a single pair of nucleotides, also known as a

muton. To indicate that a gene is functionally normal it is

assigned a plus (+) sign, whereas a damaged or mutated gene

is indicated by a minus (–) sign. A wild-type Escherichia coli

able to synthesize its own arginine would thus, be symbolized

as arg+and strains that have lost this ability by mutation of

one of the genes for arginine utilization would be arg–.Such

strains, known as arginine auxotrophs, would not be able to

grow without a supplement of arginine. At this level of defini-

tion, the plus or minus actually refer to an operonrather than

a single gene, and finer genetic analysis can be used to reveal

the exact location of the mutated gene.

The use of mutations in studying genes is well illus-

trated in a traditional genetic test called the “cis–transtest”

which also gave the gene the alternative name, cistron. This is

a complementation test that can be used to determine whether

two different mutations (m^1 and m^2 ) occur in the same func-

tional unit, i.e., within the same gene or cistron. It demon-

strates well how genes can be defined phenomenologically

and has been performed successfully in microorganismssuch

as yeasts. It works on the principle that pairs of homologous

chromosomescontaining similar genes can complementtheir

action. Two types of heterozygotes of the test organism are

prepared. Heterozygotes are organisms having different alleles

in the two homologous chromosomes each of which was

inherited from one parent. One heterozygote contains the

mutations under investigation within the same chromosome,

that is in the cis—configuration, which is symbolically desig-

nated ++/m^1 m^2 (m^1 and m^2 are the two mutations under inves-

tigation and the symbol “+” indicates the same position on the

homologous chromosome in the unmutated, wild type state).

The second mutant is constructed to contain the mutations in

such a way that one appears on each of the homologous chro-

mosomes. This is called the trans—configuration and is des-

ignated, for example, by^2 +/+m^1. If two recessive mutations

are present in the same cistron, the heterozygous trans—con-

figuration displays the mutant phenotype, whereas the cis—

configuration displays the normal, wild type, phenotype. This

is because in the cis—configuration, there is one completely

functional, unmutated, cistron (++) within the system which

masks the two mutations on the other chromosome and allows

for the expression of the wild type phenotype. If one or both

mutations are dominant, and the cis–and trans–heterozygotes

are phenotypically different, then both mutations must be

present in the same cistron. Conversely, if the cis–and trans–

heterozygotes are phenotypically identical, this is taken as evi-

dence that the mutations are present in different cistrons.

In 1910, the American geneticist Thomas Hunt Morgan

(1866–1945) began to uncover the relationship between

genes and chromosomes. He discovered that genes were

located on chromosomes and that they were arranged linearly

and associated in linkage groups, all the genes on one chro-

mosome being linked. For example the genes on the X and Y

chromosomes are said to be sex-linked because the X and Y

chromosomes determine the sex of the organisms, in humans

X determining femaleness and Y determining maleness.

Nonhomologous chromosomes possess different linkage

groups, whereas homologous chromosomes have identical

linkage groups in identical sequences. The distance between

two genes of the same linkage group is the sum of the dis-

tances between all the intervening genes and a schematic rep-

resentation of the linear arrangement of linked genes, with

their relative distances of separation, is known as a genetic

map. In the construction of such maps the frequency of

recombinationduring crossing over is used as an index of the

distance between two linked genes.

Advances in molecular geneticshave allowed analysis

of the structure and biochemistryof genes in detail. They are

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