The developmental history of genetics may be classified into three periods:- 1. Pre-Mendelian Era 2. Mendelian Era 3. Recent or Post Mendelian Era.
1. Pre-Mendelian Era:
(A) Sexuality in Plants and Animals:
This was mostly based upon theoretical concepts before 17th century. According to Harvey (1657), the animals are formed by eggs and sperm merely participate as vitalizing force, de Graaf (1673) found in progeny the characters of the male and female parents. On the basis of which he suggested that both mother and father make contribution in heredity.
Von Baer (1828) searched out eggs in dogs. Leeuwenhoek and his student Hainm studied the sperms of many animals in 1674. In 1680, Leeuwenhoek noted that sperms are associated with eggs in sexual reproduction but he did not see whether they fused or not.
Spallanzinni (1729-1799) produced puppies through artificial insemination in dogs. Oscar Hertwig (1875) conclusively proved that formation of progeny is possible from an actual fusion of male and female gametes.
N. Grew (1682) for the first time described the reproductive organs. He suggested that stamens in flowers are the male reproductive parts. Camerarious (1694) firstly described the reproductive parts or organs of the maize plant. He also showed that maize plants could not set seed unless and until the pollen was not applied to their pistils or gynoecium.
Thomas Fairchild (1717) produced first artificial hybrids in plants when he crossed sweet William with carnation. On his name this hybrid was said as “Fairchild’s mule” which contained characteristics of both the parents.
Later on, many scientists, e.g., Linnaeus (1707-1778), the father of systematic biology and Koelreuter 1733-1806, Gartner (1772-1850) etc.; produced artificial hybrids in plants and found that both the male (pollen) and female (seed) plants show equal contribution to the characters of progeny.
Amici (1823) described the entry of pollen tubes in the ovary. Strasberger (1884) described fertilization in angiosperms and noted the fusion of male and female nuclei. The above discoveries regarding artificial hybridization in plants and role of male and female gametes in fertilization has given an important contribution in the development of genetics.
(B) Preformation and Epigenesis:
Aristotle believed that the progeny derived their form from semen, while the role of females was only to provide nutrition. On the other hand Harvey (1578-1657) found that the progeny developed from egg cell and semen only worked as stimulant called aura seminalis.
In 1694 someone examining human sperms claimed that he had seen a miniature figure of human inside the sperm called “homunculus”. This view was accepted by Swammerdam and specially the Swiss naturalist Bonnet (1720-1793).
Swammerdam claimed that homunculi were found in sperms and that only the sperms contributed to heredity. This view was well supported by many biologists, said as animalculists. On other hand Bonnet idea was that homunculi were found in eggs and that only the egg cells contributed to heredity.
This idea of Bonnet was also supported by another groups of biologists said as ovists. According to these biologists the human beings were preformed in the gametes termed as preformutionism and those who supported this belief were said as performationists. Leeuwenhoek even in 1927 was also a preformationist or animalculist. He claimed to see the homunculus in sperms.
Many biologists working with well improved microscopes could not find the presence of homunculi either in sperms or eggs. Now it became evident that both views of the biologists were far away from the truth and were based on misunderstanding.
The founder of Epigenesis, C.F. Wolff (1733-1794) believed that matured or adult tissues were borne completely as a fresh (de novo) due to some mysterius “Vital forces”. He also suggested that none, i.e., egg or sperm show the presence of “homunculus”. He thought that both male and female gametes keep such a unknown living substance which after fertilization has the capacity to form a well organised body.
This concept was said as ‘theory of epigenesis’ but this concept of Wolff was opposed by his successor K.E. vonBaer (1792-1876). He proposed that adult tissues did not originate as a fresh or new (de novo) but they developed through a sequential differentiation of the embryonic tissues and no mysterious ‘vital force’ was adopted for this differentiation.
This was called Transformation theory. The concept of Wolff is universally accepted view of origin of tissues and the adult organs from the zygotes.
(C) Inheritance of acquired Characters and Pangenesis:
It was made clear by scientific studies that any organism is originated from preexisting organism of same kind, not as de novo, and the formation of adult organs is due to sequential differentiation of homogenous embryo tissue but the scientists were not aware with the facts, how that different characters of parents passes into progenies.
Lamarck (1744-1829) ‘the French biologist’ who was the father of first theory of biological evolution, considered the inheritance of the acquired characters to be transmitted in to the progenies from the generation to those in next generation. According to him, the progeny of a healthy person would also be healthy.
Likewise, the progeny of a weak person would be weak. This hypothesis is said as “Lamarckism” or “theory of inheritance of acquired characters”. It was an attractive hypothesis to explain the development of important characters of various species during evolution.
Charles Darwin (1882), more recently, Lysenko, the great scientist of Russia, became the notable supporters of “Lamarckism” or “inheritance of acquired characters” without careful tests or verification.
Biologists of 19th century including Chales Darwin (1809-1882) tried to explain the physical basis of heredity. According to him, whatever the characteristics are observed in individuals of one generation are often met with also in individuals of the next generation. Since it was already known in Darwin’s day that neither egg nor sperm contain any thing like a ‘homunculus’.
Darwin fully realized that each cell of the body produces its own rudiments which is very small, almost invisible, identical copies of itself called gemmules or pangenes, which in animals are shed in to the blood stream and then in to the gonads (the organ concerned with the production of gametes, e.g., ovary and testis in case of animals) where the gemmules are distributed into the gametes so that each gamete receives a gemmule for each of the organs of the individual.
When male and female gametes make union during fertilization, the zygote receives the gemmule from both male and female parents. During development, gemmule from both male and female parents move into the respective organs and determine the development of these organs.
If an organ of an organism or individual is modified and differentiated in some way, the gemmule will also be modified or differentiated accordingly for that organ. This modified gemmule now will be transmitted to its progeny through the gametes and will produce a similar modification in the corresponding organ of the progeny. This is called pangenesis.
It is without any scientific base and is of only historical interest. It was invalidated by Galton (1822-1911) as well as Weismann (1834-1914) very soon after its proposal. Galton transfused blood between white and black rabbits expecting reasonably to produce a mixture of gemmules which would make the offspring of the transfused parents spotted. Nothing of the sort was observed.
(D) The Germplasm Theory:
August Weismann (1834-1914), a forerunner of modern genetics, challenged the popular belief that acquired characters are inherited. He made experiments to test the validity of the hypothesis of the inheritance of acquired characters (Lamarck) and of pangenesis (Darwin). Weismann cut off the tails of a group of experimental mice for 22 successive generations.
According to the hypothesis of the inheritance of acquired characters, produced by cutting off their tails, the tailless condition of mice should be transmitted to their progeny. Likewise, if the pangenesis hypothesis were correct, the gemmule for the tail would be not found in the gametes of the tailless mice thus produced and as a result their progeny should be tailless but the result was not so far.
Weismann did not find a single tailless progeny of these mice as long as 22 generations. The above findings disproved the validity of the ideas of inheritance of acquired characters and of pangenesis. Weismann developed the germplasm theory which represented a forward step in the understanding of heredity.
According to this theory, the body of any individual is made up of two distinct type of tissues:
(i) Somatoplasm and
(ii) Germplasm.
Somtaplasm consists of body cells which are necessary for survival and functioning of the organism. These do not show any contribution in sexual reproduction.
Therefore, the changes which occur within somatoplasm, strictly can not be transmitted to the next generation. On other hand, the germplasm produces gametes that are the foundation of sexual reproduction. The changes, which occur in the germplasm are, therefore, transmitted to the next generation.
In an animal, gonads represent the germplasm and germplasm 2 show one clear difference i.e., function or in other words, the formation of gametes is made by only germplasm. It does not apply at all in the lower animals (protozoa, microbes and other single celled organism) in which no distinction can be made between soma and germ, in which many plants reproduce asexually. In such individuals a part of the somatoplasm acts as the germplasm.
“Germplasm” theory was really very significant advancement in understanding heredity since this was for the first time that a distinction between hereditary and environmental variation could be made on a perfect basis.
(E) Hybridization in Plants:
Thomas Fairchild (1717) produced the first artificial hybrid in plants when he crossed carnation with sweet William. The hybrid produced from this cross was said as Fairchild’s mule. Later on, a number of biologists worked on plant hybridization. Few of them are Joseph Koelreuter, John Knight, John Goss, Gartner, Darwin, Naudin, Sargeret, Linnaeus etc.
Koelreuter made an extensive work on Nicotiana in 1760-1766. He described the uniformity and heterosis (= Hybrid vigour = vigorousity exhibited or shown by F1 hybrid over the parents) in F1 and the appearance of a greater variation in F2.
He also said that both male and female parents make equal contribution to the characteristics of progeny since hybrids obtained from reciprocal crosses were identical. Knight (1759-1835) produced several new commercial varieties of grapes, apples, pear, apricot etc.
Through hybridization Gartner (1772-1850), Naudin (1815- 1909), Darwin and others confirmed the observations of Koelreuter and also presented evidence of dominance in F1. It became now clear that some characters of the F1 progeny resemble those of one parent, some others are similar to those of other parent, while some others are intermediate between both of the two parents.
In F1 all the plants are alike of one another but in F2 there is appearance of larger variations. The experiments and observations of these scientists provided the foundation for the historical experiments in plant by hybridization by Gregor Johann Mendel.
2. Mendel Era (Principles or Laws of Mendel):
Mendel conducted a series of experiments on hybridization in peas (Pisum sativum). The results from these experiments were published in 1866. Mendel concluded that the unit of inheritance, which he referred to as ‘factor’, now said as gene by Johannsen (1909), is particulate units or solid particles and not liquid.
The two alleles of a gene never show blending or mix together or the two alleles (an alternative form of a gene which occupy the same locus or position on the homologous chromosomes) of a gene do not affect each other in any way.
Mendel proposed two universal laws of heredity:
(1) Law of segregation and
(2) Law of independent assortment.
He also explained law of dominance. Both laws, specially law of segregation are the base of modern genetics. Therefore, Mendel is appropriately said as Father of Genetics. Mendel could not get any recognition by his contemporaries (existing at same time).
They neither understood nor appreciated the importance of his findings. His paper lay forgotten till 1900 when it was rediscovered independently by Hugo de Vries of Holland, Von Tshermak of Austria and Correns of Germany.
Genetics as a Science:
After 1900, the science of genetics has extensively developed. William Bateson (1861-1929) applied principles of Mendel in fowls. Bateson also gave the term like “Genetics”, “Homozygous” and “Heterozygous”. “Alellomorph” term was also proposed by him and he also presented “Factor hypothesis” for interaction of factors. Bateson and Punnet (1905) described the term ‘Coupling’ and ‘Repulsion’.
According to them coupling and repulsion are the two aspects of one phenomenon, i.e., linkage. Lucein Cuenot (1866-1951), a French biologist discovered ‘lethal factors’ in mice. Johannsen (1857-1927) gave the term ‘gene’ in 1909. He also proposed “The pure line theory”. He also developed the statistical methods by support of which the Mendelian principles may be analysed.
Carl Correns (1864-1933) found incomplete dominance in Mirabilis jalapa in 1903. Another classical work of Correns is on leaf variegation in Mirabilis. Hugo de Vries (1848- 1935) gave the term ‘Mutation’ and presented mutation theory in 1901. Walter Sutton (1903) proposed the chromosome theory of heredity and explained the importance of reduction division.
This type of all division was referred to as Meiosis by Farmer and Moore in 1905 and the term ‘Chromosome’ was firstly used by Waldeyer in 1888. He also concluded that genes and chromosomes show identical behaviour during cell division, fertilization, development and sexual reproduction.
He proclaimed that genes were located in chromosomes and correctly explained the laws of segregation and independent assortment of Mendel.
In the same year, Boveri gave his view that chromosomes play an important role in development and genes are found in chromosomes. Therefore, Sutton and Boveri jointly proposed “Chromosome theory of inheritance” which gave the birth of a new and exciting branch of Biology, Cytogenetics.
It is concerned with the study of various phases or aspects of chromosomes. Chromosomes are bearers of genes. The study of chromosomes provide important information about genes also.
3. Recent Advances:
Nilsson-Ehle (1909) proposed “Multiple factor hypothesis” in order to explain the inheritance of quantitative or metric characters. East and Emerson (1910) confirmed the work of Nilsson-Ehle on the basis of their own work.
According to this hypothesis, several genes (polygenes) govern the development of a single character; each of these genes has a small effect, and effect of these genes are additive or cummulative in nature. The multiple factor hypothesis has provided the genetic explanation for the inheritance of quantitative characters. This has replaced the hypothesis of blending inheritance.
T.H. Morgan (1910) proposed, linkage theory. Morgan and coworkers developed the technique of chromosome mapping through studies of linkage and prepared the first linkage map of Drosophila. Morgan for these distinguishing work was awarded the Nobel prize in 1934.
Bridge (1916) made the discovery of sex-linked inheritance in Drosophila and also proposed ‘Genic balance theory’ for sex determination. Janssens (1909) studied the behaviour and origin of chiasmata. Stern (1930) gave the evidence of cytological basis of crossing over. Muller (1927) produced artificial mutations in Drosophila by applying X-rays.
This proved a tool for inducing changes in genes and developed the possibility of desired genetic manipulations in organisms. Later in the same year, Stadler induced mutations in barley and maize by X-rays and gamma rays. This confirmed the Muller findings. Muller was given Nobel prize in 1946 for his outstanding work.
Garrod (1909) published a book ‘Inborn Errors in Metabolism’, in which he described that a person suffering from a hereditary disease lacked a particular enzyme resulting in him abnormal metabolism.
This hypothesis was well supported and represented by Beadle and Tatum (1941) on biochemical mutants from their own studies (mutants unable to synthesise, and therefore, requiring for normal growth, a specific biochemical of the common breed mold Neurospora).
They concluded that each gene forms a particular or specific enzyme which catalyses a particular or specific biochemical reaction. It is known as one gene-one enzyme hypothesis. This study established a new branch of genetics, biochemical genetics. It also pointed out the way in which a gene governs the development of a character. Beadle and Tatum including Lederberg for his extraordinary work on bacterial conjugation were awarded the Nobel prize in 1958.
Avery, Macleod and Mc Carty found that DNA (deoxyribonucleic acid) was the genetic material. Watson and Crick (1953) proposed double-helix model of DNA structure. For this important work Watson, Crick along with Wilkins were awarded Nobel prize in 1962. The double helix model of DNA is universally accepted. These discoveries laid the foundation of molecular genetics, a new branch of genetics.
Barbara Mc Clintock (1951) proposed an unusual or mutated gene called dissociation (Ds) and activator (Ac) in maize. This gene had the ability to change its position within a chromosome and also from one chromosome to another chromosome. This is the general concept of a gene as each gene is experimentally shown to occupy a fixed position or locus within a chromosome.
It never changes its location unless there is a corresponding change in the chromosome structure. The term locus is used, for this reason as a synonym for gene. It is now well known that the genes occupy fixed locus or position in the respective chromosomes.
But some genes are capable of changing their positions are said as transposable elements or transposons or more popularly called jumping genes. Mc Clintock had given the concept of jumping genes much ahead. She was awarded the Nobel prize in 1983, after thirty years of her work.
Bauer, Painter and Heitz (1937) achieved salivary gland chromosomes.
G.H. Shull (1914) developed hypothesis of heterosis. Hanning (1904) made the discovery of embryo culture which is significant for developing hybrid embryo.
Harris (1912) produced X2 (Chi-square) method. H.A. Fisher (1925) applied the statistical methods in genetics. He published research papers on genetic variation and estimation and also gave analysis of variance. Winge (1917) proposed origin of polyploids. Mc Fadden produced Triticale.
Kihara (1921) made an analytical studies of origin of Triticum aestivum. Shavel (1905) released inbred lines and produced hybrid maize. East and Shull (1905) worked together on maize breeding. East (1907-1912) developed inbred lines in maize and produced hybrid vigour too.
Hayes, Jones and others performed breeding work on hybrid maize. Hayes established maize research centre in U.S.A. Jones (1916) proposed favourable linked (additive) gene hypothesis and released double cross hybrid in 1919.
Dustin (1924) made discovery of colchicine. Blackslee and Avery (1930) also produced artificial polyploids by applying colchicine. Likewise, Nable and Ruttle (1930) also produced artificial polyploids by treatment of colchicine in other group of plants. Vavilov (1935) made discovery of ‘Theory of Centre of Origin’ in cultivated plants and law of homologous series of variation.
Karpechenko (1927) produced Raphanobrassica by crossing Raphanus satiua and Brassica oleracea. Wright and Haldane (1921 and 1924 respectively) did an important work on Biometrical genetics and made discovery of Haldane effect. Snadecor (1935) and Love (1936) have given a big contribution on correlation, regression and experimental design. Laplace proposed law of probability.
M.W. Nirenburg, F. Lipmann and Ochoa in 1961 discovered genetic code. Genetic code is also said as Triplet code because a ‘code’ is made up of three bases. They were the first to demonstrate that three uracil’s (UUU) in messenger RNA (mRNA) code for a molecule of phenyl alanine.
Later on, Nirenburg and co-workers determined the codes for other amino acids. Today the meaning of all the possible 64 codons is known. For this brilliant work Nirenburg was awarded Nobel prize in 1968. Two French scientists F. Jacob and J. Monod (1961) proposed the operation concept of gene regulation.
According to this concept, the activity of a group of structural genes (genes producing enzymes or polypeptides) is governed by three genes known as regulator, operator and promoter. This concept has already been accepted. For this tremendous work Jacob and Monod were awarded the Nobel prize in 1956. S. Benzer (1962) analysed the fine structure of gene.
He claimed three different units in genetic organisation:
(i) Cistron, the unit of gene function or polypeptide production
(ii) Muton; the unit of mutation or the smallest part of gene where mutation may occur
(iii) Recon, the smaller part of gene in which recombination can take place.
Ochoa (1956) received in vitro synthesis of ribonucleic acid (RNA). In the same year, Romberg developed the technique for in vitro synthesis of DNA. Both were jointly awarded Nobel prize in 1959 for their valuable achievements.
A scientist of Indian origin, Dr. Hargovind Khorana for his famous work on genetic code and in-vitro (when biological processes are made to occur outside the organism in vessel or test tube) synthesis of DNA, was awarded the Nobel prize in 1968.
A brief survey of developments in genetics between 1900 to up-to-date demonstrates that this branch of biology has come a long way from the point of beginning. It has provided almost a clear understanding of the phenomena of heredity and variation.
Recently, techniques for the production of recombinant DNA have already been developed which may provide the desired modification in genes. Man may be able to synthesise a desired gene and change the direction of organic evolution.
This is really the greatest achievement of this science which may give an unlimited power to control his own fate. Recombinant DNA technology is a boon for human welfare. It will be a saddest day for humanity if this powerful tool was put to a destructive uses.