Genetic Research After Mendel

Chromosome, microscopic, threadlike part of the cell that carries hereditary information in the form of genes; among simple organisms, such as bacteria and algae, chromosomes consist entirely of DNA and are not enclosed within a membrane; among all other organisms chromosomes are contained in a membrane-bound cell nucleus and consist of both DNA and RNA; arrangement of components in the DNA molecules determines the genetic information; every species has a characteristic number of chromosomes, called the chromosome number; in species that reproduce asexually the chromosome number is the same in all the cells of the organism; among sexually reproducing organisms, each cell except the sex cell contains a pair of each chromosome.

Weismann, August (1834-1914), German biologist; advanced theory that changes in the characteristics of a species are due to changes in germ plasm.

Sutton, Walter S. (1876-1916), U.S. geneticist and physician; noted for studies of chromosomes.

Boveri, Theodor Heinrich (1862-1915), German scientist whose work with roundworm eggs proved that chromosomes are separate, continuous entities within the nucleus of a cell.

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 recognized 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.

Morgan, Thomas Hunt (1866-1945), U.S. zoologist, born in Lexington, Ky.; professor Columbia University 1904-28; director of biological laboratories, California Institute of Technology; received 1933 Nobel prize for work on role of chromosomes in heredity; wrote books on embryology, evolution, and heredity.

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.

Beadle, George Wells (1903-89), U.S. biologist, born near Wahoo, Neb.; professor and chairman of biology division California Institute of Technology 1946-60, acting dean of faculty 1960-61; president University of Chicago 1961-68; director Institute of Biomedical Research, AMA, 1968-70; received 1958 Nobel prize for work in biochemical and microbial genetics.

Tatum, Edward Lawrie (1909-75), U.S. biochemist, born in Boulder, Colo.; professor Yale University 1946-48, Stanford University 1948-57, and Rockefeller University 1957-75; received 1958 Nobel prize for discovery that genes act by controlling specific chemical processes.

Avery, Oswald Theodore (1877-1955), U.S. bacteriologist who determined that deoxyribonucleic acid (DNA) is the basic genetic material of the cell.

Watson, James Dewey (born 1928), U.S. biochemist, born in Chicago, Ill.; on staff Harvard University 1955-68, professor 1961-68; director Cold Spring Harbor Laboratory from 1968; received 1962 Nobel prize for discovery of molecular structure of DNA.

Crick, Francis Harry Compton (born 1916), British biochemist; on staff Cavendish Laboratory, Cambridge University 1949-77; professor Salk Institute for Biological Studies from 1977; received 1962 Nobel prize for discovery of molecular structure of DNA; elected to U.S. National Academy of Sciences 1969.

Jacob, Francois (born 1920), French biologist, born in Nancy; with Pasteur Institute from 1950, College de France from 1964; received 1965 Nobel prize for work in genetics.

Monod, Jacques (1910-76), French biologist, born in Paris; with Pasteur Institute from 1945, director from 1971; received 1965 Nobel prize for work in genetics; researched protein metabolism and RNA.

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 make-up of a human being.

Recombinant DNA, genetically engineered DNA prepared in vitro by cutting up DNA molecules and splicing together specific DNA fragments; usually uses DNA from more than one species of organism.

Clone, process of biologically purifying a gene from one species by inserting it into the DNA of another species where it is replicated along with the host DNA; used to manufacture insulin.

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. 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.

The 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 fertilizes 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 bivalents 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 fertilizes 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 synthesized during the lengthy interphase as well as during the relatively short period of cell division.

Late in the interphase, DNA is synthesized and daughter chromosomes are created. First, DNA is made. Soon afterwards, 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 non alleles 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.

Sex Linkage

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 fertilizes 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

Genes, the 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

Nucleic acid, any of substances comprising genetic material of living cells; divided into two classes: RNA (ribonucleic acid) and DNA (deoxyribonucleic acid); directs protein synthesis and is vehicle for transmission of genetic information from parent to offspring.

The 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.

Adenine, a purine base that codes hereditary information in the genetic code in DNA and RNA.

Cytosine, pyrimidine base that codes genetic information in DNA or RNA.

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.

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.

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 anti codons, nucleotide triplets that pair their bases with mRNA codons. Thus, AAA is the anti codon for UUU. When a codon specifies a particular amino acid during protein synthesis, the tRNA molecule with the anti codon 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 anti codon 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.

Mutations

Down’s syndrome (or mongolism), a congenital condition with moderate to severe mental retardation; characteristic features include: broad flat faces, slanted eyes, small ears and noses; heart defects and other abnormalities.

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.

Assisted by Val W. Woodward

Genetic Terms

allele. 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.

dominance. 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 make-up of an organism, which may include genes for the traits that do not show up in the phenotype.

heterozygous. Containing dissimilar alleles.

homozygous. Containing a pair of identical alleles.

phenotype. The visible characteristics of an organism (for example, height and colouration).

recessiveness. The masking of one member of an allelic pair by the other in the phenotypes of heterozygotes.