Why do human children resemble their
parents? Why do the offspring of any species resemble their parents? Biologists have shown that the factors which cause such resemblance are passed on relatively unaltered from one generation to the next by a
process called heredity. Resemblance, they say, is transmitted by genes, cell units too tiny to be seen even with a microscope. The branch of biology that deals with genes is called genetics.
Man has speculated about heredity throughout known history. In ancient Greece, for example, it was thought that the blood was in some way
responsible for the transmission of hereditary traits, and the word "blood" is still often used to mean ancestry. Since the beginning of the 20th century, however, genes have been known to be the carriers
of traits, though until the 1940s very little was known about them. Scientists recognised that genes were directly responsible for the characteristics of an organism and that genes were transmitted from parents to
offspring. However, they had little idea of the gene structure and composition that made these actions possible.
By the 1950s scientists had learned a great deal about the chemistry of genes. Genes
were found to be segments of certain complex molecules located in the cell nucleus. The molecules have the unique ability to duplicate themselves and, in so doing, to pass on body-building instructions to the next
generation of a species.
THE ORIGINS OF MODERN GENETICS
Even before the beginnings of written history people were aware of some of the ways in which
heredity takes place. The domesticated animals and plants of today are proof of this. Today's horses, cattle, dogs, corn, wheat, and cotton differ greatly from their primitive, "wild" ancestors. They are
products of the ancient breeders' art, an art that included the proper selection of parents, well-controlled mating, and the careful choice of the best offspring to further improve a breed.
Early Theories of Heredity
Over the centuries more became known about the control of heredity for practical purposes. However, scientists remained baffled about the actual processes of trait transmission. All sorts of what
proved to be erroneous explanations were advanced. In the 17th century, for example, a group of biologists called the ovists held that the ovaries of females contained the hereditary material and that the male sperm
merely triggered embryonic development. Other scientists were of the opinion that tiny but fully formed creatures were present in the sperm.
Early in the 19th century the French biologist Jean
Baptiste Lamarck suggested that traits and abilities acquired during the lifetime of an organism could be transmitted to future generations. This theory was termed "the inheritance of acquired
characteristics." Long before Lamarck, notions of this kind had led expectant mothers to practice the piano, gaze at beautiful pictures, or think "kind" thoughts in the hope that this would affect the
character of their unborn children. For similar reasons, many breeders exposed plants and animals to the environmental conditions their breeding programs were intended to combat. Genetic discoveries in the mid-1800s
proved Lamarck's view to be mistaken.
Two Pioneers of Genetics
In 1859 the English biologist Charles Darwin published his epic 'The Origin of Species', an attempt to demonstrate that
all living things are related through the common bond of evolution (see Evolution). Darwin assumed that all species produce more offspring than reach maturity. Those offspring that survive and reproduce, he
reasoned, do so because they are better suited to the existing environment. Because environment changes with time, he argued, species must either adapt to the new conditions or become extinct. Darwin did not know
just what mechanisms made it possible for such changes in species to take place. He recognised, however, that if his theory were correct, changeable, or mutable, units of heredity must exist and that variations in
species must arise as a result of an accumulation of small changes in these units of heredity.
In 1865 Gregor Mendel, a monk in an Austrian Roman Catholic monastery, wrote a paper that laid the
foundation for modern genetics. Mendel was the first to demonstrate experimentally the manner in which specific traits are passed on from one generation to the next. He concluded that "discrete hereditary
elements" (not called genes until the 1900s) in the sex cells are responsible for the transmission of traits. Mendel was ahead of his time, however. The significance of his work was not realised until 1900.
Mendel's Contributions to Genetics
In the monastery garden where he conducted his experiments, Mendel observed the inheritance of traits in the easily available garden pea, Pisum
sativum.The plant is an ideal genetic working material because a number of progeny can be produced in a short time and because its reproductive parts are so constructed that accidental fertilisation is nearly
Mendel began by tracing the inheritance of one or two contrasting traits at a time. Thus, he crossed tall peas with short peas or red-flowered peas with white-flowered peas. Then he
recorded how many of the progeny developed each of the contrasting traits. He used the progeny in subsequent mating to follow the progress of the traits under study through a number of generations.
From the evidence obtained in this way, Mendel reasoned that contrasting traits are governed by units of inheritance existing in pairs in somatic, or body, cells but singly in gametes, or sex cells. If
the genotype R stands for red and the genotype r for white, then homozygous red-flowered peas have RR somatic cells and R gametes. The somatic cells and gametes of homozygous white-flowered peas are, by contrast, rr
and r, respectively.
The separation of alleles (R from r, for example) in gamete formation is called the principle of segregation. Mendel correctly assumed that chance determines which gene of a
pair finds its way into a given gamete. A red-flowered pea may be a heterozygous, or hybrid, Rr. That is, in some way the allele for red flowers (R) "dominates" the allele for white flowers (r). However,
the R and r alleles of the hybrid segregate during sex-cell division to produce an equal number of R and r gametes. This is proved by test crossing the hybrid with a homozygous white (rr) plant. Since the homozygous
white produces only r gametes and the hybrid produces both R and r gametes, the ratio of red plants to white plants is one to one.
Mendel also demonstrated that non allelic genes (for tall or short
and red or white phenotypes, for example) segregate independently of one another into the gametes. This phenomenon is called the principle of independent assortment. For example, a cross between pure strains of tall
plants with red flowers (TTRR) and short plants with white flowers (ttrr) produces hybrid progeny that are all tall with red flowers (TtRr). A testators between these tall, red hybrids (TtRr) and short, white pure
strains (ttrr) results in four equally distributed types of progeny, 25 percent tall, red TtRr, 25 percent short, red ttRr, 25 percent tall, white Ttrr, and 25 percent short, white ttrr. Modern geneticists have
learned, however, that independent assortment does not always hold true because non alleles located side by side on the same chromosome tend to be inherited as a package.
Genetic Research After Mendel
Chromosomes, structures in the cell nucleus that carry genes, were discovered after Mendel's work was published. However, accurate accounts of their behaviour were not generally available until
about 1885. Earlier the German biologist August Weismann had suggested that heredity depends on a special material called germ plasma that is transmitted unaltered from one generation to another. In the 1880s
Weismann and other scientists advanced the idea that the germ plasm was located in the chromosomes. In 1902 Walter S. Sutton of the United States and Theodor Boveri of Germany independently recognised the connection
between the segregation of alleles as described by Mendel and the segregation of homologous pairs of chromosomes in the division of sex cells.
In 1910 the American geneticist Thomas H. Morgan
and his associates discovered that genes occur on chromosomes and that those genes lying close together on the same chromosome form linkage groups that tend to be inherited together. They also showed that linkage
groups often break apart naturally as a result of a phenomenon called crossing over.
In the 1940s George W. Beadle and Edward L. Tatum of the United States began to investigate the role played
by genes in the production of enzymes. By 1944 Oswald T. Avery had discovered that deoxyribonucleic acid (DNA) was the basic genetic material of the cell. The precise molecular structure of DNA was determined in
1953 by James D. Watson of the United States and Francis H.C. Crick of England. By 1961 the French geneticists Francois Jacob and Jacques Monod had developed a model for the process by which DNA directs the
synthesis of proteins, thereby deciphering, in principle, the genetic code of the DNA molecule. In 1988 an international team of scientists began a project to devise a map of the human genome, all the genes that
determine the makeup of a human being.
Since the 1970s the techniques of recombinant DNA have allowed researchers to biologically purify, or clone, a gene from one species by inserting it into the
DNA of another species, where it is replicated along with the host DNA. In this manner human hormones, such as insulin and growth hormone, have been manufactured economically by colonies of bacteria.
CHROMOSOMES AND CELL DIVISION
Chromosomes are mainly aggregates of deoxyribonucleic acid (DNA) and protein (see Protein). All but the simplest kinds of plants and animals inherit two sets
of chromosomes (the diploid number), one set (the haploid number) from each parent. In humans, each somatic cell has a haploid set of 23 chromosomes from each parent, for a total of 46.
chromosomes within each set vary in appearance. However, each has a homologous partner in the other set, which resembles it in both appearance and genetic characteristics. A given gene is found on only a particular
chromosome in each set. Its allele is on that chromosome's homologue in the other set. The alleles are passed on to new cells during mitosis, the division of somatic cells.
Mitosis takes place
as soon as a sperm fertilises an egg. It continues throughout the life of the organism. Prior to mitosis, the cell chromosomes make exact copies of themselves. At this point, twice the diploid number of chromosomes
exist in the cell. As mitosis proceeds, one set of the doubled chromosomes goes into each of the two daughter cells. Each thus acquires a full diploid set of chromosomes. This process is repeated again and again as
cells divide and the body grows. Sex cells, however, divide in a different way.
Sex cells in the adult reproductive organs produce gametes by meiosis. This process consists of two divisions.
As the first division proceeds, the homologous chromosomes in the nucleus of the sex cell seek each other out and join, or synapse. They are called bivalent at this point.
Then the bivalents
duplicate themselves to form a bundle, or tetrad, or four intertwined chromatids. The tetrads then thicken and separate, and a pair of homologous chromatids pass into each of two daughter cells.
Meiosis does not stop at this stage, however. The two daughter cells, still with a diploid number of chromosomes, undergo a second division, the reduction division. In this division, the homologous
chromatids do not duplicate themselves but merely separate and pass randomly into two additional cells, where they thicken into chromosomes. In meiosis, each sex cell produces four gametes, each with a haploid
number of chromosomes (only one allele is in each gamete). When a male gamete fertilises an egg, the diploid number of chromosomes is restored.
Chromosomes are fully visible under a microscope
during the four stages of cell division, prophase, metaphase, anaphase, and telophase. However, between the telophase and the next prophase a lengthy period called the interphase occurs, during which the chromosomes
are too thin and strung out to be seen. Important chemical activities take place during the interphase. Ribonucleic acid (RNA), chemically related to DNA, and proteins are synthesised during the lengthy interphase
as well as during the relatively short period of cell division.
Late in the interphase, DNA is synthesised and daughter chromosomes are created. First, DNA is made. Soon afterward, in a burst of
activity, chromosomal DNA, RNA, and protein are fitted together, the chromosomes begin to take shape, and cell division begins. During sex cell division, however, an important gene exchange between homologous
chromosomes takes place.
Linked Non alleles and Crossing Over
As meiosis takes place, homologous chromosomes exchange some of their genes. This phenomenon is known as crossing over.
Although the process is not well understood, it is thought that a reciprocal breakage and rejoining of homologous chromatids occurs while the tetrads are intertwined during early meiosis.
Geneticists began to investigate crossing over when they noted that the traits actually inherited did not always adhere to the principle of independent assortment. Test crosses between AaBb and aabb parents - A, a,
B, and b representing the dominant and recessive genes of nonalleles - did not always produce equal numbers of AaBb, aaBb, Aabb, and aabb progeny but a greater number of the parental types AaBb and aabb and a
smaller number of the recombinant types Aabb and aaBb. Geneticists concluded that the dominant non alleles A and B were linked together on one homologous chromosome and that the recessive non alleles a and b were
linked together on the other. If this linkage were unbreakable, in meiosis the hybrid AaBb would form only AB and ab gametes. In fact, however, Ab and aB gametes were also formed, the frequency varying for different
linked non alleles. It was therefore surmised that an exchange, or crossing over, took place.
Linked genes occur on the sex chromosomes as well as on the non sex
chromosomes, or autosomes. In humans, a woman carries two X chromosomes and 44 autosomes in each body cell and one X chromosome and 22 autosomes in each egg. A man carries one X and one Y chromosome and 44 autosomes
in each body cell and either an X or a Y chromosome and 22 autosomes in each sperm cell.
Only sons inherit traits carried by genes located on the Y chromosome, because a boy (XY) develops whenever
a Y sperm fertilises an egg. Traits carried on genes located on an X chromosome of the father are transmitted only to daughters (XX).
GENES AND THE GENETIC CODE
arbiters of body form and organ function, work with precision. They transmit to each cell a genetic code that determines the cell's purpose.
Nucleic Acids -The Key to Heredity
structure of DNA makes gene transmission possible. Since genes are segments of DNA, DNA must be able to make exact copies of itself to enable the next generation of cells to receive the same genes.
The DNA molecule looks like a twisted ladder. Each "side" is a chain of alternating phosphate and deoxyribose sugar molecules. The "steps" are formed by bonded pairs of
purine-pyrimidine bases. DNA contains four such bases, the purines adenine (A) and guanine (G) and the pyrimidines cytosine (C) and thymine (T).
The RNA molecule, markedly similar to DNA, usually
consists of a single chain. The RNA chain contains ribose sugars instead of deoxyribose. In RNA, the pyrimidine uracil (U) replaces the thymine of DNA.
DNA and RNA are made up of basic units called
nucleotides. In DNA, each of these is composed of a phosphate, a deoxyribose sugar, and either A, T, G, or C. RNA nucleotides consist of a phosphate, a ribose sugar, and either A, U, G, or C.
Nucleotide chains in DNA wind around one another to form a complete twist, or gyre, every ten nucleotides along the molecule. The two chains are held fast by hydrogen bonds linking A to T and C to G, A always pairs
with T (or with U in RNA); C always pairs with G. Sequences of the paired bases are the foundation of the genetic code. Thus, a portion of a double-stranded DNA molecule might read: A-T C-G G-C T-A G-C C-G A-T. When
"unzipped," the left strand would read: ACGTGCA; the right strand: TGCACGT.
DNA is the "master molecule" of the cell. It directs the synthesis of RNA. When RNA is being
transcribed, or copied, from an unzipped segment of DNA, RNA nucleotides temporarily pair their bases with those of the DNA strand. In the preceding example, the left hand portion of DNA would transcribe a strand of
RNA with the base sequence: UGCACGU.
Genes and Protein Synthesis
A genetic code guides the assembly of proteins. The code ensures that each protein is built from the proper sequence of amino
acids (see Protein).
Genes transmit their protein-building instructions by transcribing a special type of RNA called messenger RNA (mRNA). This leaves the cell nucleus and moves to structures in
the cytoplasm called ribosomes, where protein synthesis takes place (see Cell).
Cell biologists believe that DNA also builds a type of RNA called transfer RNA (tRNA), which floats freely
through the cell cytoplasm. Each tRNA molecule links with a specific amino acid. When needed for protein synthesis, the amino acids are borne by tRNA to a ribosome.
For years biologists wondered
how amino acids were guided to fit together in the exact sequences needed to produce the thousands of kinds of proteins required to sustain life. The answer seems to lie in the way the four genetic "code
letters" - A, T, C, and G - are arranged along the DNA molecule.
The Genetic Code
Experimental evidence indicates that the genetic code is a "triplet" code; that is,
each series of three nucleotides along the DNA molecule orders where a particular amino acid should be placed in a growing protein molecule. Three-nucleotide units on an mRNA strand, for example UUU, UUG, and GUU,
are called codons. The codons, transcribed from DNA, are strung out in a sequence to form mRNA.
According to the triplet theory, tRNA contains anticodons, nucleotide triplets that pair their bases
with mRNA codons. Thus, AAA is the anticodon for UUU. When a codon specifies a particular amino acid during protein synthesis, the tRNA molecule with the anticodon delivers the needed amino acid to the bonding site
on the ribosome.
The genetic code consists of 64 codons. However, since these codons order only some 20 amino acids, most, if not all, of the amino acids can be ordered by more than one of
them. For example, the mRNA codons UGU and UGC both order cysteine. Because mRNA is a reverse copy of DNA the genetic code for cysteine is ACA or ACG. Some codons may act only to signal a halt to protein synthesis.
To illustrate the operation of the genetic code, assume that one protein is responsible for the development of brown hair and that this protein is composed of three amino acid molecules arranged in
linear sequence, for example, cysteine-cysteine-cysteine. (This is a much simplified example, since proteins actually incorporate from 100 to 300 amino acid molecules.) The gene (DNA segment) specifying formation of
this protein reads: ACAACAACA. It produces the mRNA segment UGUUGUUGU. This segment then drifts to a ribosome. Three tRNA molecules, each with the cysteine-bearing anticodon ACA, line up in order on the ribosome and
deposit their cysteine to make the brown-hair protein.
Since code transmission from DNA to mRNA is extremely precise, any error in the code affects protein synthesis. If the error is serious
enough, it eventually affects some body trait or feature.
Certain chemicals and types of radiation can cause mutations, changes in the structure of genes or chromosomes. The
simplest type of mutation is a change in the DNA or RNA nucleotide sequence. Mutations may also involve the number of chromosomes or the gain, loss, or rearrangement of chromosome segments. If a mutation occurs in
parental sex cells, the change is passed on to the offspring. In humans, an extra chromosome in body cells (47 instead of 46) has been implicated in Down's syndrome, a serious mental abnormality.
Most mutations are considered harmful and are, therefore, eventually eliminated. Some, however, enable an organism to adapt to a changing environment. Biologists believe that mutations have caused the many genetic
changes involved in the evolution of species.
. One of the members of a gene pair, each of which is found on chromosomes; the pair of alleles determines a specific trait.
chromosome. A structure in the cell nucleus containing genes.
The expression of one member of an allelic pair at the expense of the other in the phenotypes of heterozygotes. gene. One of the chromosomal units that transmit specific hereditary traits; a segment of the self-reproducing molecule, deoxyribonucleic acid.
genotype. The genetic makeup of an organism, which may include genes for the traits that do not show up in the phenotype.
heterozygous. Containing dissimilar alleles.
Containing a pair of identical alleles.
phenotype. The visible characteristics of an organism (for example, height and coloration).
The masking of one member of an allelic pair by the other in the phenotypes of heterozygotes.