Genetics can be simply defined as the manipulation of DNA to study cellular
and organismal functions. Since DNA encodes all of the information needed to
make the cell and the complete organism, the effects of changing this molecule
can give clues to the normal functions of the cell and organism.
Before the advent of methods for manipulating DNA in the test tube,
the only genetic approaches available for studying cellular and organismal
functions were those of classical
genetics. In this type of analysis, mutants (i.e., individuals that differ
from the normal, or wild-type, members of the species by a certain observable
attribute, or phenotype) that have alterations in the function being studied
are isolated. The changes in the DNA, or mutations, responsible for the altered
function are then localized in the chromosome by genetic crosses. The mutations
are then grouped into genes by allelism tests to determine how many different
genes are involved. The functions of the genes can then sometimes be deduced
from the specific effects of the mutations on the organ- ism. The ways in which
mutations in genes involved in a biological system can alter the biological
system provide clues to the normal functioning of the system.
Classical genetic analyses continue to contribute greatly to our
understanding of developmental and cellular biology. A major advantage of the
classical genetic approach is that mutants with a function altered can be
isolated and characterized without any a priori understanding of the molecular
basis of the function. Classical genetic analysis is also often the only way to
determine how many gene products are involved in a function and, through
suppressor analysis, to find other genes whose products may interact either
physically or functionally with the products of these genes.
The development of molecular
genetic techniques has greatly expanded the range of methods available for
studying genes and their functions. These techniques include methods for
isolating DNA and identifying the regions of DNA that encode particular
functions, as well as methods for altering or mutating DNA in the test tube and
then returning the mutated DNA to cells to determine the effect of the mutation
on the organism.
The approach of first cloning a gene and then altering it in the
test tube before reintroducing it into the cells to determine the effects of
the alterations is sometimes called reverse
genetics and is essentially the reverse of a classical genetic analysis. In
classical genetics, a gene is known to exist only because a mutation in it has
caused an observable change in the organism. With the molecular genetic
approach, a gene can be isolated and mutated in the test tube without any
knowledge of its function. Only after the mutated gene has been returned to the
organism does its function become apparent.
Rather than one approach supplanting the other, molecular genetics
and classical genetics can be used to answer different types of questions, and
the two approaches often complement each other. In fact, the most remarkable
insights into biological functions have often come from a combination of classical
and molecular genetic approaches.
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