I INTRODUCTION
Genetics,
scientific study of how physical, biochemical, and behavioral traits are
transmitted from parents to their offspring. The word itself was coined in 1906
by the British biologist William Bateson. Geneticists are able to determine the
mechanisms of inheritance (see Heredity)
because the offspring of sexually reproducing organisms do not exactly resemble
their parents, and because some of the differences and similarities between
parents and offspring recur from generation to generation in repeated patterns.
The investigation of these patterns has led to some of the most exciting
discoveries in modern biology.
II EMERGENCE
OF GENETICS
The science of genetics began in 1900, when several
plant breeders independently discovered the work of the Austrian monk Gregor
Mendel, which, although published in 1866, had been virtually ignored. Working
with garden peas, Mendel described the patterns of inheritance in terms of seven
pairs of contrasting traits that appeared in different pea-plant varieties. He
observed that the traits were inherited as separate units, each of which was
inherited independently of the others (see Mendel’s Laws). He suggested
that each parent has pairs of units but contributes only one unit from each pair
to its offspring. The units that Mendel described were later given the name genes.
III PHYSICAL
BASIS OF HEREDITY
Soon after Mendel’s work was rediscovered, scientists
realized that the patterns of inheritance he had described paralleled the action
of chromosomes in dividing cells, and they proposed that the Mendelian units of
inheritance, the genes, are carried by the chromosomes. This led to intensive
studies of cell division.
Every cell comes from the division of a preexisting
cell. All the cells that make up a human being, for example, are derived from
the successive divisions of a single cell, the zygote (see
Fertilization),which is formed by the union of an egg and a sperm. The great
majority of the cells produced by the division of the zygote are, in the
composition of their hereditary material, identical to one another and to the
zygote itself. Each cell of a higher organism is composed of a jellylike layer
of material, the cytoplasm, which contains many small structures. This
cytoplasmic material surrounds a prominent body called the nucleus. Every
nucleus contains a number of minute, threadlike chromosomes. Some relatively
simple organisms, such as cyanobacteria and bacteria, have no distinct nucleus
but do have cytoplasm, which contains one or more chromosomes.
Chromosomes vary in size and shape and usually occur in
pairs. The members of each pair, called homologues, closely resemble each other.
Most cells in the human body contain 23 pairs of chromosomes, whereas most cells
of the fruit flyDrosophila contain four pairs, and the bacteriumEscherichia
coli has a single chromosome in the form of a ring. Every chromosome in a
cell is now known to contain many genes, and each gene is located at a
particular site, or locus, on the chromosome.
The process of cell division by which a new cell comes
to have an identical number of chromosomes as the parent cell is called mitosis
(see Reproduction). In mitotic division each chromosome divides into two
equal parts, and the two parts travel to opposite ends of the cell. After the
cell divides, each of the two resulting cells has the same number of chromosomes
and genes as the original cell. Every cell formed in this process thus has the
same array of genetic material. Simple one-celled organisms and some
multicellular forms reproduce by mitosis; it is also the process by which
complex organisms achieve growth and replace worn-out tissue.
Higher organisms that reproduce sexually are formed
from the union of two special sex cells known as gametes. Gametes are produced
by meiosis, the process by which germ cells divide. It differs from mitosis in
one important way: In meiosis a single chromosome from each pair of chromosomes
is transmitted from the original cell to each of the new cells. Thus each gamete
contains half the number of chromosomes that are found in the other body cells.
When two gametes unite in fertilization, the resulting cell, called the zygote,
contains the full double set of chromosomes. Half of these chromosomes normally
come from one parent and half from the other.
IV THE
TRANSMISSION OF GENES
The union of gametes brings together two sets of genes,
one set from each parent. Each gene—that is, each specific site on a
chromosome that affects a particular trait—is therefore usually represented by
two copies, one coming from the mother and one from the father. Each copy is
located at the same position on each of the paired chromosomes of the zygote.
When the two copies are identical, the individual is said to be homozygous for
that particular gene. When they are different—that is, when each parent has
contributed a different form, or allele, of the same gene—the individual is
said to be heterozygous for that gene. Both alleles are carried in the genetic
material of the individual, but if one is dominant, only that one will be
manifested. In later generations, however, as was shown by Mendel, the recessive
trait may show itself again (in individuals homozygous for its allele).
For example, the ability of a person to form pigment in
the skin, hair, and eyes depends on the presence of a particular allele (A),whereas
the lack of this ability, known as albinism, is caused by another allele (a)
of the same gene. (For convenience, alleles are usually designated by a single
letter; the dominant allele is represented by a capital letter and the recessive
allele by a small letter.) The effects of A are dominant; of a,
recessive. Therefore, heterozygous persons (Aa), as well as persons
homozygous (AA) for the pigment-producing allele, have normal
pigmentation. Persons homozygous for the allele that results in a lack of
pigment (aa) are albinos. Each child of a couple who are both
heterozygous (Aa) has a probability of one in four of being homozygous AA,
one in two of being heterozygous Aa, and one in four of being homozygous aa.
Only the individuals carrying aa will be albino. Note that each child has
a one-in-four chance of being affected with albinism; it is not accurate to say
that one-quarter of the children in a family will be affected. Both alleles will
be carried in the genetic material of heterozygous offspring, who will produce
gametes bearing one or the other allele. A distinction is made between the
appearance, or outward characteristics, of an organism and the genes and alleles
it carries. The observable traits constitute the organism’s phenotype, and the
genetic makeup is known as its genotype.
Not always is one allele dominant and the other
recessive; instead, the inheritance of both sometimes results in intermediate
characteristics. The four-o’clock plant, for example, may have flowers that
are red, white, or pink. Plants with red flowers have two copies of the allele R
for red flower color and hence are homozygous RR. Plants with white
flowers have two copies of the allele r for white flower color and are
homozygous rr. Plants with one copy of each allele, heterozygous Rr,
are pink—a blend of the colors produced by the two alleles.
The action of genes is seldom
a simple matter of a single gene controlling a single trait. Often one gene may
control more than one trait, and one trait may depend on many genes. For
example, the action of at least two dominant genes is required to produce purple
pigment in the purple-flowered sweet pea. Sweet peas that are homozygous for
either or both of the recessive alleles involved in the color traits produce
white flowers. Thus, the effects of a gene can depend on which other genes are
present.
V QUANTITATIVE
INHERITANCE
Traits that are expressed as variations in quantity or
extent, such as weight, height, or degree of pigmentation, usually depend on
many genes as well as on environmental influences. Often the effects of
different genes appear to be additive—that is, each gene seems to produce a
small increment or decrement independent of the other genes. The height of a
plant, for example, might be determined by a series of four genes: A, B, C,
and D. Suppose that the plant has an average height of 25 cm (10 in) when
its genotype is aabbccdd, and that each replacement by a pair of dominant
alleles increases the average height by approximately 10 cm (about 4 in). In
that case a plant that is AABBccdd will be 46 cm (18 in) tall, and one
that is AABBCCDD will be 66 cm (26 in) tall. In reality, the results are
rarely as regular as this. Different genes may make different contributions to
the total measurement, and some genes may interact so that the contribution of
one depends on the presence of another. The inheritance of quantitative
characteristics that depend on several genes is called polygenic inheritance. A
combination of genetic and environmental influences is known as multifactorial
inheritence.
VI GENE
LINKAGE AND GENE MAPPING
Mendel’s principle that genes controlling different
traits are inherited independently of one another turns out to be true only when
the genes occur on different chromosomes. The American geneticist Thomas Hunt
Morgan and his coworkers, in an extensive series of experiments using fruit
flies (which breed rapidly), showed that genes are arranged on the chromosomes
in a linear fashion; and that when genes occur on the same chromosome, they are
inherited as a single unit for as long as the chromosome itself remains intact.
Genes inherited in this way are said to be linked.
Morgan and his group also
found, however, that such linkage is rarely complete. Combinations of alleles
characteristic of each parent can become reassorted among some of their
offspring. During meiosis, a pair of homologous chromosomes may exchange
material in a process called recombination, or crossing-over. (The effect of
crossing-over can be seen under a microscope as an X-shaped joint between the
two chromosomes.) Crossovers occur more or less at random along the length of
the chromosomes, so the frequency of recombination between two genes depends on
their distance from each other on the chromosome. If the genes are relatively
far apart, recombinant gametes will be common; if they are relatively close,
recombinant gametes will be rare. In the offspring produced by the gametes, the
crossovers show up as new combinations of visible traits. The more crossovers
that occur, the greater the percentage of offspring that show the new
combinations. Consequently, by arranging suitable breeding experiments,
scientists can plot, or map, the relative positions of the genes along the
chromosome.
In recent years geneticists
have used organisms such as bacteria, molds, and viruses, which rapidly produce
extremely large numbers of offspring, to detect recombinations that occur only
rarely. Thus, they are able to make maps of genes that are quite close together.
The method introduced at Morgan’s laboratory has now become so exact that
differences occurring within a single gene can be mapped. These maps have shown
that not only do the genes occur in linear fashion along the chromosome, but
they themselves are linear structures. The detection of rare recombinants can
reveal the existence of structures even smaller than those observed through the
most powerful microscopes.
Studies of fungi, and more
recently of fruit flies, have shown that recombination of alleles can sometimes
take place without reciprocal exchanges between chromosomes. Apparently, when
two different versions of the same gene occur together (in a heterozygote), one
of them may be "corrected" to match the other. Such corrections may
take place in either direction (for example, the allele A may be changed
to a, or vice versa). This process has been called gene conversion.
Occasionally, several adjacent genes may undergo conversion together, and the
likelihood of two genes being coconverted is related to their distance apart.
This provides another way of mapping the relative positions of genes on the
chromosome.
The most recent techniques of
gene mapping, known as physical mapping, use genetic material cloned by
high-technology methods such as polymerase chain reaction (PCR) and combine
robotics, lasers, and computers to measure the distance between genetic markers
on the chromosome (see Human Genome Project).
VII SEX
AND SEX LINKAGE
Another contribution to genetic studies made by Morgan
was his observation in 1910 of sexual differences in the inheritance of traits,
a pattern known as sex-linked inheritance.
Sex is usually determined by
the action of a single pair of chromosomes. Abnormalities of the endocrine
system or other disturbances may alter the expression of secondary sexual
characteristics, but they almost never completely reverse the sex. A human
female, for example, has 23 pairs of chromosomes, and the members of each pair
are much alike. A human male, however, has 22 similar pairs and one pair
consisting of two chromosomes that are dissimilar in size and structure. The 22
pairs of chromosomes that are alike in both males and females are called
autosomes. The remaining chromosomes, in both sexes, are called the sex
chromosomes. The two identical sex chromosomes in the female are called X
chromosomes. One of the sex chromosomes in the male is also an X chromosome, but
the other, shorter one is called the Y chromosome. When gametes are formed, each
egg produced by the female contains one X chromosome, but the sperm produced by
the male can contain either an X or a Y chromosome. The union of an egg, which
always bears an X chromosome, with a sperm also bearing an X chromosome produces
a zygote with two X’s: a female offspring. The union of an egg witha sperm
that bears a Y chromosome produces a male offspring. Modifications of this
mechanism occur in various plants and animals.
The human Y chromosome is
approximately one-third as long as the X, and apart from its role in determining
maleness, it appears to be genetically inactive. Thus, most genes on the X have
no counterpart on the Y. These genes, said to be sex-linked, have a
characteristic pattern of inheritance. The hereditary blood disease hemophilia,
for example, is usually caused by a sex-linked recessive gene (h). A
female with HH or Hh is normal; a female with hh has
hemophilia. A male is never heterozygous for the gene because he inherits only
the gene that is on the X chromosome. A male with H is normal; with h
he has hemophilia. When a normal man (H) and a woman who is heterozygous
(Hh) have offspring, the female children are normal, but half of them
carry the h gene—that is, none of them is hh, but half of them
bear the genotype Hh. The male children inherit only the H or the h;
therefore, half the male children have hemophilia. Thus, in normal circumstances
a female carrier passes on the disease to half her sons, and she also passes on
the recessive h gene to half her daughters, who in turn become carriers
of hemophilia. Many other conditions—including red-green color blindness,
hereditary nearsightedness, night blindness, and ichthyosis (a skin disease)—have
been identified as sex-linked traits in humans.
VIII GENE
ACTION: DNA AND THE CODE OF LIFE
For more than 50 years after the science of genetics
was established and the patterns of inheritance through genes were clarified,
the largest questions remained unanswered: How are the chromosomes and their
genes copied so exactly from cell to cell, and how do they direct the structure
and behavior of living things? Two American geneticists, George Wells Beadle and
Edward Lawrie Tatum, provided one of the first important clue s in the early
1940s. Working with the fungi Neurospora and Penicillium, they
found that genes direct the formation of enzymes through the units of which they
are composed. Each unit (a polypeptide) is produced by a specific gene. This
work launched studies into the chemical nature of the gene and helped to
establish the field of molecular genetics.
That chromosomes were almost
entirely composed of two kinds of chemical substances, protein and nucleic
acids, had long been known. Partly because of the close relationship established
between genes and enzymes, which are proteins, protein at first seemed the
fundamental substance that determined heredity. In 1944, however, the Canadian
bacteriologist Oswald Theodore Avery proved that deoxyribonucleic acid (DNA)
performed this role. He extracted DNA from one strain of bacteria and introduced
it into another strain. The second strain not only acquired characteristics of
the first but passed them on to subsequent generations. By this time DNA was
known to be made up of substances called nucleotides. Each nucleotide consists
of a phosphate, a sugar known as deoxyribose, and any one of four
nitrogen-containing bases (see Acids and Bases). The four nitrogen bases
are adenine (A), thymine (T), guanine (G), and cytosine (C).
In 1953, putting together the accumulated chemical
knowledge, geneticists James Dewey Watson of the U.S. and Francis Harry Compton
Crick of Great Britain worked out the structure of DNA. This knowledge
immediately provided the means of understanding how hereditary information is
copied. Watson and Crick found that the DNA molecule is composed of two long
strands in the form of a double helix, somewhat resembling a long, spiral
ladder. The strands, or sides of the ladder, are made up of alternating
phosphate and sugar molecules. The nitrogen bases, joining in pairs, act as the
rungs. Each base is attached to a sugar molecule and is linked by a hydrogen
bond to a complementary base on the opposite strand. Adenine always binds to
thymine, and guanine always binds to cytosine. To make a new, identical copy of
the DNA molecule, the two strands need only unwind and separate at the bases
(which are weakly bound); with more nucleotides available in the cell, new
complementary bases can link with each separated strand, and two double helixes
result. If the sequence of bases were AGATC on one existing strand, the new
strand would contain the complementary, or "mirror image," sequence
TCTAG. Since the "backbone" of every chromosome is a single long,
double-stranded molecule of DNA, the production of two identical double helixes
will result in the production of two identical chromosomes.
The DNA backbone is actually a
great deal longer than the chromosome but is tightly coiled up within it. This
packing is now known to be based on minute particles of protein known as
nucleosomes, just visible under the most powerful electron microscope. The DNA
is wound around each nucleosome in succession to form a beaded structure. The
structure is then further folded so that the beads associate in regular coils.
Thus, the DNA has a "coiled-coil" configuration, like the filament of
an electric light bulb.
After the discoveries of
Watson and Crick, the question that remained was how the DNA directs the
formation of proteins, compounds central to all the processes of life. Proteins
are not only the major components of most cell structures, they also control
virtually all the chemical reactions that occur in living matter. The ability of
a protein to act as part of a structure, or as an enzyme affecting the rate of a
particular chemical reaction, depends on its molecular shape (see
Molecule). This shape, in turn, depends on its composition. Every protein is
made up of one or more components called polypeptides, and each polypeptide is a
chain of subunits called amino acids. Twenty different amino acids are commonly
found in polypeptides.The number, type, and order of amino acids in a chain
ultimately determine the structure and function of the protein of which the
chain is a part.
A The
Genetic Code
Since proteins were shown to be products of genes, and
each gene was shown to be composed of sections of DNA strands, scientists
reasoned that a genetic code must exist by which the order of the four
nucleotide bases in the DNA could direct the sequence of amino acids in the
formation of polypeptides. In other words, a process must exist by which the
nucleotide bases transmit information that dictates protein synthesis. This
process would explain how the genes control the forms and functions of cells,
tissues, and organisms. Because only four different kinds of nucleotides occur
in DNA, but 20 different kinds of amino acids occur in proteins, the genetic
code could not be based on one nucleotide specifying one amino acid.
Combinations of two nucleotides could only specify 16 amino acids (42 = 16), so
the code must be made up of combinations of three or more successive
nucleotides. The order of the triplets—or, as they came to be called, codons—could
define the order of the amino acids in the polypeptide.
Ten years after Watson and
Crick reported the DNA structure, the genetic code was worked out and proved
biologically. Its solution depended on a great deal of research involving
another group of nucleic acids, the ribonucleic acids (RNA). The specification
of a polypeptide by the DNA was found to take place indirectly, through an
intermediate molecule known as messenger RNA (mRNA). Part of the DNA somehow
uncoils from its chromosome packing, and the two strands become separated for a
portion of their length. One of them serves as a template upon which the mRNA is
formed (with the aid of an enzyme called RNA polymerase). The process is very
similar to the formation of a complementary strand of DNA during the division of
the double helix, except that RNA contains uracil (U) instead of thymine as one
of its four nucleotide bases, and the uracil (which is similar to thymine) joins
with the adenine in the formation of complementary pairs. Thus, a sequence
adenine-guanine-adenine-thymine-cytostine (AGATC) in the coding strand of the
DNA produces a sequence uracil-cytosine-uracil-adenine-guanine (UCUAG) in the
mRNA.
B Transcription
The production of a strand of mRNA by a particular
sequence of DNA is called transcription. While the transcription is still taking
place, the mRNA begins to detach from the DNA. Eventually one end of the new
mRNA molecule, which is now a long, thin strand, becomes inserted into a small
structure called a ribosome, in a manner much like the insertion of a thread
into a bead. As the ribosome bead moves along the mRNA thread, the end of the
thread may be inserted into a second ribosome, and so on. Using a very
high-powered microscope and special staining techniques, scientists can
photograph mRNA molecules with their associated ribosome beads.
Ribosomes are made up of
protein and RNA. A group of ribosomes linked by mRNA is called a polyribosome or
polysome. As each ribosome passes along the mRNA molecule, it "reads"
the code, that is, the sequence of nucleotide bases on the mRNA. The reading,
called translation, takes place by means of a third type of RNA molecule called
transfer RNA (tRNA), which is produced on another segment of the DNA. On one
side of the tRNA molecule is a triplet of nucleotides. On the other side is a
region to which one specific amino acid can become attached (with the aid of a
specific enzyme). The triplet on each tRNA is complementary to one particular
sequence of three nucleotides—the codon—on the mRNA strand. Because of this
complementarity, the triplet is able to "recognize" and adhere to the
codon. For example, the sequence uracil-cytosine-uracil (UCU) on the strand of
mRNA attracts the triplet adenine-guanine-adenine (AGA) of the tRNA. The tRNA
triplet is known as the anticodon.
As tRNA molecules move up to
the strand of mRNA in the ribosome beads, each bears an amino acid. The sequence
of codons on the mRNA therefore determines the order in which the amino acids
are brought by the tRNA to the ribosome. In association with the ribosome, the
amino acids are then chemically bonded together into a chain, forming a
polypeptide. The new chain of polypeptide is released from the ribosome and
folds up into a characteristic shape that is determined by the sequence of amino
acids. The shape of a polypeptide and its electrical properties, which are also
determined by the amino acid sequence, dictate whether it remains single or
becomes joined to other polypeptides, as well as what chemical function it
subsequently fulfills within the organism.
In bacteria, viruses, and
cyanobacteria (formerly known as blue-green algae), the chromosome lies free in
the cytoplasm, and the process of translation may start even before the process
of transcription (mRNA formation) is completed. In higher organisms, however,
the chromosomes are isolated in the nucleus and the ribosomes are contained only
in the cytoplasm. Thus, translation of mRNA into protein can occur only after
the mRNA has become detached from the DNA and has moved out of the nucleus.
C Introns
A recent and unexpected discovery is that in higher
organisms the genes are interrupted. Within the length of a sequence of
nucleotides that codes a particular polypeptide may be one or more interruptions
by noncoding sequences; within some genes as many as 50 or more of these
intervening sequences, or introns, may be found. During transcription the
introns are copied into RNA along with the coding sequences, producing an
extra-large RNA molecule. The sequences corresponding to the introns are then
exactly chopped out of the RNA, by special enzymes in the nucleus, to form the
mRNA that is exported to the cytoplasm.
The functions (if any) of
introns are not understood, although the suggestion has been made that the
processing of RNA by chopping out the intervening sequences may be involved in
regulating the quantity of polypeptide produced by the gene. Introns have also
been found in genes that code for special RNAs, such as those that are
components of the ribosomes. The discovery of introns was made possible by new
methods of determining the exact sequence of nucleotides in molecules of DNA and
RNA. These methods were developed by the British molecular biologist Frederick
Sanger; for this work he received a second Nobel Prize in chemistry in 1980.
D Repeated
Sequences Direct studies of DNA have also
shown that, in higher organisms, some sequences of nucleotides are repeated many
times throughout the genetic material. Some of these repeated sequences
represent multiple copies of genes that code polypeptides, or of genes that code
special RNAs (almost always, there are many copies of genes that produce the RNA
components of ribosomes). Other repeated sequences do not seem to code
polypeptides or RNAs. Among them are sequences that seem able to jump from place
to place in a chromosome, from one chromosome to another, and even from one
species to another. These transposons, or transposable elements—informally
known as jumping genes—are able to attach to other DNA sequences, causing
mutations in the genes adjacent to their points of arrival or departure.
Transposons were first discovered in the 1940s by Nobel laureate Barbara
McClintock in her research on maize but have since been found in every species.
Much research is now focused on transposons, and many scientists suspect that
these transposable elements may be a key to evolutionary change, helping to
increase the genetic variation of a species.
IX GENE
REGULATION Knowing how protein is made
allows scientists to understand how genes can produce specific effects on the
structures and functions of organisms. This does not explain, however, how
organisms can change in response to changing environmental circumstances, or how
a single zygote can give rise to all the different tissues and organs that make
up a human being. Most of the cells in these tissues and organs contain
identical sets of genes but nevertheless make different proteins; clearly, in
the cells of any one tissue or organ some genes are acting but others are not.
Different tissues have different arrays of genes in the active state. Thus, part
of the explanation for the development of a complex organism must lie in the
ways by which genes are specifically activated.
The processes of gene
activation in higher organisms are still obscure, but through the work of the
French geneticists François Jacob and Jacques Lucien Monod, a good deal is
known about these processes in bacteria. Near each bacterial gene is a segment
of DNA known as the promoter. This is the site at which RNA polymerase, the
enzyme responsible for the production of mRNA, sticks to the DNA and starts
transcription. Between the promoter and the gene there is often a further
segment of DNA called the operator, where another protein—the repressor—can
stick. When the repressor is attached to the operator, it stops the RNA
polymerase from moving along the chromosome and producing mRNA; consequently,
the gene is inactive. The presence of a chemical substance in the cell, however,
may cause the repressor to become detached and the gene to become active. Other
substances may affect the degree of gene activity by altering the ability of the
RNA polymerase to bind to the promoter. The repressor protein is produced by a
gene called the regulator.
In bacteria, several genes may
be controlled simultaneously by one promoter and one or more operators. The
entire system is then called an operon. Apparently, operons do not occur in
complex organisms, but quite possibly each gene has its own individual system of
promoters and operators, and introns and repeated sequences may also play a
role.
X CYTOPLASMIC
INHERITANCE Some constituents of the cell
besides the nucleus contain DNA. They include the cytoplasmic bodies known as
mitochondria (the energy producers of the cell) and the chloroplasts of plants,
where photosynthesis takes place. These bodies are self-reproducing. The DNA is
replicated in a manner similar to that in the nucleus, and sometimes its code is
transcribed and translated into proteins. In 1981 the entire sequence of
nucleotides in the DNA of a mitochondrion was determined; apparently,
mitochondria use a code only slightly different from that used by the nucleus.
The traits determined by
cytoplasmic DNA are more often inherited through the mother than through the
father, because sperm and pollen usually contain less cytoplasmic material than
do eggs. Some cases of apparent maternal inheritance are actually due to the
transmission of viruses from mother to offspring through the egg cytoplasm.
XI MUTATIONS
Although the replication of DNA is very
precise, it is not uniformly perfect. Very rarely, changes occur in DNA during
replication, and the new piece of DNA contains one or more changed nucleotides.
Such a change, known as a mutation, may take place in any part of the
DNA. If a mutation occurs in the sequence of nucleotides that codes for a
particular polypeptide, it may change an amino acid in the polypeptide chain.
This change may seriously alter the properties of the resulting protein. For
example, the polypeptides distinguishing normal hemoglobin and sickle-cell
hemoglobin (see Sickle-Cell Anemia) differ by only a single amino acid.
When a mutation occurs during the formation of gametes, it will be passed on to
the following generation.
A Gene
Mutation Mutations were first reported in
1901 by the Dutch botanist Hugo De Vries, one of Mendel’s rediscoverers. In
1929 the American biologist Hermann Joseph Muller found that the rate of
mutation can be increased greatly by X rays. Later, other forms of radiation, as
well as high temperatures and various chemicals, were also found to be capable
of inducing mutations. The mutation rate can also be increased by the presence
of particular alleles of certain genes, known as mutator genes, some of which
seem to cause defects in the mechanisms maintaining the fidelity of DNA
replication. Gene mutations can also occur as the result of transposons.
Most gene mutations are
harmful to the organisms that carry them; the function of a complex system such
as a protein is more easily destroyed than improved by a random change. Thus,
the number of individuals carrying a particular mutant gene at any time is
usually the consequence of two opposing forces: The tendency for the number to
increase because of the reproduction of new mutant individuals in a population,
and the tendency for the number to decrease because mutant individuals survive
or reproduce less well than their peers. Human activities have tended to make
the increase in the number of individuals carrying mutant genes larger because
of exposure to medical X rays, radioactive materials (see Radioactivity),
and mutation-causing chemicals.
Gene mutations due to
transposons seem to follow a different rule. Recent research has shown that such
genetic mutations are more likely to improve the evolutionary fitness of a
species than are other types of mutations.
Mutations are usually
recessive, and their harmful effects are not expressed unless two of them are
brought together into the homozygous condition. This is most likely to occur as
a result of inbreeding, the mating of closely related organisms that may have
inherited the same recessive mutant gene from a common ancestor. For this
reason, inherited diseases are more common among children whose parents are
cousins than they are in the human population as a whole.
B Chromosome
Mutations The substitution of one
nucleotide for another is not the only possible kind of mutation. Sometimes a
nucleotide may be entirely lost or one may be gained. In addition, more dramatic
and obvious changes may occur, or the chromosomes themselves may alter in form
or number. A section of chromosome may become detached, turn over, and then
reattach to the chromosome at the same site. This is called an inversion. If the
detached section unites with a different chromosome, or a different part of the
original chromosome, it is called a translocation. Sometimes a piece of
chromosome will be lost from one member of a pair of homologous chromosomes and
gained by the other member. One of the pair is then said to have a deficiency
and the other a duplication. Deficiencies are usually lethal in the homozygous
condition, and duplications are often so. Inversions and translocations are more
frequently viable, although they may be associated with mutations in genes near
the points where the chromosomes have been broken. Most of these chromosomal
rearrangements are probably the consequences of errors in the process of
crossing over.
Another kind of mutation
occurs when a pair of homologous chromosomes fails to separate at meiosis. This
can produce gametes—and hence zygotes—with extra chromosomes and others with
one or more chromosomes missing. Individuals with an extra chromosome are known
as trisomics, and those with a missing chromosome as monosomics. Both conditions
tend to result in severe disabilities. For example, people with three copies of
the 21st chromosome are born with Down syndrome.
Sometimes an entire set of
chromosomes may fail to separate at meiosis; thus, a gamete with twice the
normal number of chromosomes is produced. If such a gamete fuses with one
containing the normal number of chromosomes, the offspring will have three
homologous sets rather than the normal two. If two gametes with twice the normal
number fuse, the offspring will have four homologous sets. Organisms with
additional sets of chromosomes are known as polyploids. Polyploidy is the only
known process by which new species may arise in a single generation. Viable and
fertile polyploids are found almost exclusively in hermaphroditic organisms (see
Hermaphroditism), such as most flowering plants and some invertebrate animals.
Plant polyploids are usually larger and sturdier in form than their normal
diploid ancestors. Polyploid fetuses sometimes occur in humans, but they die at
an early stage of fetal development and are aborted (see Genetic
Disorders).
XII GENES
IN POPULATIONS Population genetics, which
investigates how genes spread through populations of organisms, was given a firm
basis by the work of the English mathematician Godfrey H. Hardy and the German
obstetrician Wilhelm Weinberg. In 1908 they independently formulated what is now
known as the Hardy-Weinberg rule. This states that if two alleles of one
autosomal gene (A and a) exist in a population, if their
frequencies of occurrence (expressed in decimals) are p and q,
respectively (p + q = 1), and if mating between individuals occurs
at random with respect to the gene, then after one generation the frequencies of
the three genotypes AA, Aa, and aa will be p2, 2pq,
and q2, respectively. These frequencies, in the absence of disturbances,
will then remain constant from generation to generation. Any change of
frequency, which signals an evolutionary change, must therefore be due to
disturbances. These disturbances may include mutation, natural selection,
migration, and breeding within small populations that may lose particular
alleles by chance, or random genetic drift (see Evolution).
Evidence indicates that most
populations are a great deal more variable genetically than was supposed.
Studies of the polypeptide products of genes have suggested that, on the
average, about one-third of them have genetic variants at frequencies higher
than could be expected from the balance between their generation by mutation and
the selective disadvantage of the mutants. This has led to increased interest in
the ways by which alternate alleles may be actively maintained in a state of
balance so that neither replaces the other. One such balancing mechanism is
heterozygous advantage, when the heterozygote survives better than either of the
homozygotes. Another balancing mechanism, called frequency-dependent selection,
depends on the relative advantage of rare varieties, for example, in populations
subject to predators. Predators tend to concentrate on the variety that is
common and to disregard rarer types. Thus, a variety can be at an advantage when
it is rare but may begin to lose the advantage as natural selection for the
protective trait makes it more common. Predators then begin to kill off the
once-favored variety until at last an equilibrium is reached between the alleles
in the population. Parasites may act in a similar fashion, becoming specialized
to attack whichever is the commonest variety of host and thereby maintaining
genetic variability in host populations.
XIII HUMAN
HEREDITY Most physical characteristics of
humans are influenced by multiple genetic variables as well as by the
environment. Some characteristics, such as height, have a relatively large
genetic component. Others, such as body weight, have a relatively large
environmental component. Still other characteristics, such as the blood groups (see
Blood Type) and the antigens involved in the rejection of transplanted organs (see
Transplantation, Medical), appear to involve entirely genetic components; no
environmental condition is known to change these characteristics. The
transplantation antigens have recently been extensively studied because of their
medical interest. The most important ones are produced by a group of linked
genes known as the HLA complex. This group of genes not only determines whether
transplanted organs will be accepted or rejected, it is also involved in the
body’s resistance to various diseases (including allergies, diabetes, and
arthritis).
Susceptibility to various
other diseases has an important genetic element. These diseases include
Huntington’s disease (see Chorea), Alzheimer’s disease, diabetes
mellitus, multiple sclerosis (MS), schizophrenia, malaria, several forms of
cancer, migraine headaches, alcoholism, obesity, and high blood pressure. Many
rare diseases are caused by recessive genes and a few by dominant genes.
The identification and study of genes are of great
interest to biologists, and are also of medical importance when a particular
gene is involved in disease. The human genome contains approximately 50,000 to
100,000 genes, of which about 4000 may be associated with disease. A coordinated
effort, called the Human Genome Project, was started in 1990 to characterize the
entire human genome. The primary goal of the Human Genome Project is the
generation of various genome maps, including the entire nucleotide sequence of
the human genome. The Human Genome Project has been greatly assisted by the
ability to clone large fragments of DNA into yeast artificial chromosome vectors
for further analysis, and the automation of many techniques such as DNA
sequencing.
See also
Gene; Genetic Engineering; Heredity; Hybrid; Natural Selection; Plant Breeding.
Contributed By:
Bryan C. Clarke
Further Reading
