Short essay on the Development of Genetic

Initial Ideas on Heredity

(A) Ideas of Hippocrates and Aristotle:

Earliest writings on the subject of heredity are those of Hippocrates (400 BC) and Aristotle (350 BC). Hippocrates believed that characters are inherited from parents because reproductive material is handed over from all parts of the body of an individual.

Aristotle could not agree with Hippocrates, because this could not explain inheritance of characters like nails, hair, voice, grey hairs etc. because most of these are dead tissues and could not have contributed to reproductive tissue. Aristotle also pointed out cases where children may resemble their grandparents rather than their parents. He believed that reproductive material was not derived from different parts but from nutrient substances meant for different parts and diverted to reproductive path.

These nutrient substances would differ depending upto different parts for which they are meant. He also believed that female sex contributed the material and the male sex contributed something to define the form of the embryo. Both of them believed in direct inheritance of traits, which are handed over from parents to offsprings, through reproductive material. This is the simplest theory of inheritance, which do not hold good today.

(B) Preformation and epigenesis:

In 1679, J. Swammerdam studied development of insects and suggested that development of an organism is simple enlargement of a minute but preformed individual, “which was called “homunculus” and could be present in sperm or in the ovum. But it could not be accepted. K.F. Wolff (1738-1794), proposed that neither egg nor sperm had a homunculus like structure but that the gametes contained undifferentiated living substances capable of forming the organized body after fertilization. Such an idea was called the theory of “epigenesis”.

(C) Pangenes & Acquired Characters:

J.B. Lamarck (1744-1829). Characters which are acquired during the lifetime of an individual are inherited. This concept is known as Lamarckism or “The Theory of Inheritance of Acquired Characters”. This theory was very popular in the eighteenth century to explain evolution and heredity. However Lamarck did not point out the physical basis of this theory.

Charles Darwin (1809-1882) tried to suggest that every part of the body produced very small invisible bodies called “gemmules” or “pangenes”, which are transported through the blood stream to the sex organs and are assembled into gamates. During fertilization, gemmules from both parents are brought together for redistribution to different organs during development, thus determining different characters. This theory is almost a copy of Lamarck’s theory except that it suggested a physical basis.

(D) Experiments of Knight & Goss on Pea:

Knight (1799) and Goss (1824) had conducted experiments on edible pea (Pisum sativum), much before Mendel, but failed to formulate the law of inheritance, only because they could not give a mathematical treatment of their results. They were more concerned for improvement of peas rather than their concern for understanding the mechanism.

(E) Germplasm Theory and the Genotype Phenotype Concept:

A. Weismann (1834-1914) demonstrated that “Pangenesis” could not be verified. His popular experiments consisted of cutting the tails of mice and then studying the inheritance. Repeating such a treatment for 22 generations, he found that complete tail structure was still inhibited.

There experiments of mutilation may appear now rather crude, but results can definitely be used as argument against “pangenesis” because one the tail was removed, the ‘pangenes’ or ‘gemmules’ for the tail will not be available and therefore this structure should not develop in the next generation if pangenesis holds good.

Weismann also proposed his own germplasm theory to account for heredity. According to this theory, the body of an individual can be divided into “germplasm” and “somatoplasm”. The somatoplasm was not able to enter the sex cells consequently the variations present in the somatoplasm will not be transmitted to next generation. The germplasm on the other hand, was meant for the reproductive purpose only, so that any change occurring in germplasm will influence the progeny. This was very significant advancement in understanding of heredity.

In order to make definite distinction between hereditary and environmental variations, Johannsen, 1909, formulated the genotype- phenotype concept. According to him the genotype of an individual represents sum total of heredity.

On the other hand, phenotype represents features which are produced by interaction between genotype and environment.

A genotype can thus exhibit different phenotype under different conditions. This is referred to as individidual’s “norm of reaction” to the environment. Therefore similar genotypes may not have the same phenotype. Conversely, similar phenotypes do not necessarily mean some genotype.

(F) Gregor Mendel (1822-1884) is appropriately called “father of genetics”. Mendel (1865) discovered the laws of heredity by studying crosses between peas having pair of contrasting characters (i.e. allelic). In across between parents with yellow seeds and parents with green seeds, he found that in F, generation, all the hybrid had yellow seeds (dominant gene).

In the F₂ generation 75% of the plant had yellow seeds and 25% had green seeds (recessive gene). Mendel postulated that the genes are transmitted without mixing (law of segregation). He demonstrated that in F₂ there are 1 dominant homozygous, 2 heterozygous and 1 ressive homozygous offsprings. The ‘genotypic’ segregation is 1 : 2 : 1 although the “phenotypic” proportion is 3 : 1. The law of segregation can be explained in terms of the behaviour of chromosomes during meiosis. At times there is incomplete dominance (i.e. intermediary heredity).

The behaviour of two or more pairs of allelic genes follows the “law of independent assortment”. Genes that lie in different chromosomes are independently distributed during meiosis. For the two pairs of alleles, the phenotypic proportion is 9:3:3:.

Mendel was not the first to perform hybridization experiments, but he was the first to consider the results in terms of single traits. Sageret. (1826) had studied the inheritance of contrasting traits. Others of Mendel’s predecessors had considered whole organism, which incorporate a nebulous complex of traits, thus, they could observe only that similarity and differences occurred among parents and progeny.

They missed the significance of individual differences. Employing the scientific method, Mendel designed the necessary experiments, counted and classified the peas resulting from his crosses, compared the proportions with mathematical models, and formulated a hypothesis for their differences.

Although Mendel devised a precite mathematical pattern for the transmission of hereditary units, he had no concept of the biological mechanisms involved. Nevertheless, on the basis of his preliminary experiments and hypotheses, he predicted and subsequently verified his predictions with the results of later crosses.

In 1990, Mendel’s paper was discovered simultaneously by three botanists :

(0 Hugo de Vries in Holland-Known for his mutation theory and studies on the evening primrose and maize.

(ii) Carl Correns in Germany-who investigated maize, peas, beans.

(iii) Eric von Tschermak-Seysenegy in Austria- who worked with several plants, including garden pea.

Each of their investigators obtained evidence for Mendel’s principles from his own independent studies. They all found Mendel’s report while searching the literature for related work and cited it in their own publications.

(G) William Bateson, an Englishman, gave this developing science the name “GENETICS” is 1905. He coined the term from a Greek word meaning “to generate”.

(H) Concept of the Gene:

(a) Bateson actively promoted Mendel’s view of paired genes. He used the word “Allelomorph”, shortened to allele to identify members of pairs that control different alternative traits.

(b) During early 1800s, a Frenchman, Lucien Cuenot, showed that genes controlled fur colour in the mouse.

(c) An American. W.E. Castle related genes to sex and to fur colour and pattern is mammals.

(d) A Dane and W.L. Johannsen, studied the influence of heredity and environment in plants. He began using the word gene from the last syllable of Darwin’s term “pangene”.

The gene concept however had been implicit in Mendel’s visualization of a physical element or factor that acts as the foundation for development of a trait. These men and their peers were able to build on the basic principles of cytology, which were established between 1865 (when Mendel’s work was completed) and 1900 (when it was discovered).

(I) Chromosome Theory:

(a) Wilhelm Roux has postulated as early as 1883 that chromosomes within the nucleus of the cell were the bearers of hereditary factors. The only model he was able to devise that would account for his observed genetic result was a row of lined-up objects duplicated exactly. To explain the mechanics of gene transmission from cell to cell he, therefore, suggested that nuclei must have invisible structures held in rows or chains that duplicated themselves when the cell divided. Constituents of the nuclei that seemed best designed to carry genes and fill there requirements were chromosomes.

(b)In 1900, Von Winiwarter, discovered that in the ovary of a half day old rabbit (Oryctolagus cuniculus) chromosomes had associated in pairs side by side for a part of their length. This association appeared at what are now call zygotene stage of meiosis, which was very common in rabbits ovary 1/½ & 2½days old.

(c) Montgomery (1901), after a study of meiosis in 42 species of insects came to conclusion that each association of chromosomes in pairs at zygotene involves one paternal & one maternal chromosome.

(d) Sutton (1902) extended Montgomery’s observation while studying meiosis in grasshopper. The male grasshopper has 23 chromosomes in somatic cells, and their chromosomes differed very much in size, so that the largest chromosome was 5-6 times as long as the smallest. Sutton observed that apart from one X-chromosome, 11 -paired associations were present in each nucleus and showed same size differences as at mitosis.

It was also shown that although due to degree of contraction, absolute lengths of paired chromosomes differed at different stages of meiosis, but their relative lengths were constant. This confirmed Montgomery’s conclusion that association were brought about only between paternal and maternal chromosomes.

(e) T. Boveri (1902):

Who demonstrated in sea urchin, that different chromosomes of a set possess different qualities and also showed presence of a complete set of chromosomes was important for survival. This observation derives support now from the fact that a hypodiploid (chromosome no. < 2) does not survive while a haploid individual may survive. It is also proved by the fact that trisomies involving different chromosomes differed morphologically as in case of Detura and many other plant species and also in Human.

(f) Experiments of T. Boveri & W.S. Sutton in 1902 brought confirming evidence that a gene is part of a chromosome. The theory of the gene as a discrete unit of a chromosome was developed by T.H. Morgan and his associates from studies on the fruit fly, Drosopliila melanogaster.

(g) H.J. Muller later promoted the merger of the two sciences that had contributed most to the chromosome theory-cytology (the study of cells) and genetics as CYTOGENETICS.

(J) Formulation of Chromosome Theory:

On the basis of findings of Montgomeny and Boveri and on the basis of his own studies, W.S. Sutton for the first time in 1903 formulated chromosome theory of Mendelian inheritance in clear terms. He drew attention to following features which suggested that Mendelian factors should be located on chromosomes:

(i) There is a resemblance between separation of homologus chromosomes during anaphase I of meiosis and the postulated separation of character differences at the time of gamete formation.

(ii) If each pair of homologous chromosome is so oriented at metaphase I, so that in a pair the orientation of maternal and paternal chromosomes, towards specific poles is independent of the orientation of these chromosomes in the other pair, we expect that 2″ combinations are possible (n = haploid chromosomes number).

This is true of Mendelian factors also. This will further suggest that in Sea Urchin with n- 18, = 262, 144 possible combinations of maternal and paternal chromosomes will be available. Therefore, there is a parallelism between presumed independent assortment of homologous chromosomes at meiosis and Mendel’s prinsiple of independent assortment. Confirmation of random orientation of different chromosome pairs came by use of sex chromosomes.

(K) Sex Chromosome and Chromosome Theory:

(a) The first definite evidence for chromosome theory came from sex-determination. C.E. Mc Clung in 1902 reported two types of sperms in grasshoppers, one containing an X-chromosome and the other lacking it. Since this was the only difference in sperms and since all eggs were similars with respect to X- chromosome it was concluded that x-chromosome must be responsible for determination of sex.

(b) Proof of parallelism between chromosomes and mendelian factors with respect to independent assortment came from E.E. Carothers in 1913. She used a particular grasshopper of three pairs of chromo­some could be morphologically distinguished. If these three pairs are designated as AA’, BB’ & CC’, the possible arrangements at metaphase I can be shown as in following figure:

AA’ AA	AA’	AA’
BB’ BB’	B’B	BB’
CC’ CC’	CC’	C’C
A’A A’A	AA’	A’A
B’B BB’	B’B	B’B
CC’ C’C	C’C	C’C

Eight types of combinations in gametes would then be possible in equal proportions from arrange­ments shown in the above figure. When crosses of thus marked grasshoppers were made with normal grasshoppers, all eight combinations could be identified morphologically through cytological preparations, suggesting an assortment just like that for mendelian factors in a trihybrid cross.

Mendel had fortunately selected those characters which were located on separate chromosomes. Had he selected two characters located on the same chromosome, independent assortment would not be observed, since chromosomes and not part thereof, will exhibit independent assortment. A very strong cytological evidence for chromosome theory of inheritance came from C. Stern’s experiment on crossing over & C.B. Bridge’s experiment on the non­disjunction of X-chromosomes.