In this article we will discuss about the chromosome theory of inheritance.
In order to understand the role played by chromosomes as carriers of hereditary material, we must turn the clock backward to some landmarks in the history of genetics. The earliest records date back to the work of the 18th Century plant hybridisers. One of them Kolreuter had some theoretical knowledge on the basis of his practical experience in hybridisation work on Nicotiana.
He crossed Nicotiana rustica with N. paniculata and found that for all 13 characters studied by him, the resulting hybrid was intermediate between the two parents. The results of his reciprocal crosses were the same. Thus he was first to suggest that the hereditary contribution of the two parents to their offspring was equal.
The later half of the 19th century then covered a few more milestones in genetics. Oscar Hertwig in 1876 studied fertilisation in sea urchins while Strasburger (1877,1884) and Schmitz (1879) made similar observations in plants. Hertwig noted the presence of two nuclei in the fertilised egg and concluded that fertilisation involved fusion of nuclei from two parental gametes.
Working with seed plants, Strasburger in 1884 could clearly show that in the orchid Orchis latifolia the pollen tube travels downward through the pistil and enters the embryo sac. But the existence of a hereditary substance inside the nucleus was first postulated by August Weismann working as Professor at the University of Freiburg. He called the substance germplasm.
The next problem was to understand the continuity of the germplasm i.e. its transmission from parent to offspring. It was Schneider in 1873 who first demonstrated the continuity of germplasm (nucleus) through cell division by observing condensing chromosomes and their movements in dividing eggs of the flatworm Mesostomum.
Walter Flemming in 1878 was first to study mitosis in detail and coined the term. He could observe metaphase chromosomes longitudinally split in half and their movement apart to each of the two daughter nuclei. In this way a parent cell could pass on two identical groups of chromosomes to its two daughter cells.
Another evidence for the role of chromosomes in heredity came when E. Van Beneden and Weismann showed that gametes contained only half the number of chromosomes present in somatic tissues and that the somatic number was restored at fertilisation.
In 1883 Wilhelm Roux went a step further by suggesting that cell division not only divides the quantity of nuclear material, but also its properties or individual qualities (hereditary determinants of a trait).
The cytological studies on chromosomes conducted till 1900 constitute the first or pre-mendelian phase in the development of the Chromosome Theory of Inheritance. But after the rediscovery of Mendelism, all efforts were directed towards determining the relationship between Mendelian factors and chromosomes.
In Mendel’s crosses, the F2 progeny segregated in typical ratios as expected on theoretical grounds. But the cytological basis of Mendelism was not understood until the behaviour of chromosomes during cell division was known.
In 1902 Correns provided evidence that segregation of Mendelian factors occurred during meiotic division. In 1901 Montgomery made the important observation that during meiosis maternal chromosomes paired only with paternal chromosomes.
He studied a very favourable material Ascaris megalocephala var. univalens which has only two chromosomes. Obviously when there is pairing it must involve a maternal and a paternal chromosome.
In 1902 McClung could associate a specific heritable trait in grasshopper with a specific chromosome. In the same year Theodor Boveri studied multipolar mitoses in sea urchin embryos and concluded that the individual chromosomes are qualitatively distinct from each other and carry different hereditary determinants.
Boveri’s conclusion was further strengthened by the observations of Walter Sutton in 1903 who could demonstrate morphological differences between the 23 chromosomes of the grasshopper Brachystola.
Sutton was a graduate student of Wilson at Columbia University and is credited for demonstrating a parallel between meiotic behaviour of paired chromosomes and the behaviour of pairs of Mendelian factors. He could explain Mendel’s principle of segregation by showing cytologically that in meiosis one member of a pair of homologous chromosomes goes to one daughter cell, the other to the second daughter cell.
Mendel’s second principle of independent assortment found cytological proof from the fact that members of one pair of homologous chromosomes move to the poles independently of the members of another pair. In this way the final mixture of chromosomes (paternal and maternal) at a pole is different from one cell to another.
In other words, segregation of paired homologues at Metaphase I occurs at random. This phenomenon was also demonstrated explicitly by Carothers, a student of McClung, in grasshopper in which one pair of homologous chromosomes is such that one member is larger than the other partner. Moreover there is one unpaired chromosome in the grasshopper.
She observed separation of the two unequal chromosomes to the two poles in about 300 cells and found that the unpaired chromosome passed to one pole with the larger homologue in about 50% of cells, and with the smaller homologue in the remaining 50% cells. From this she inferred that different chromosome pairs assort independently.
Boveri’s work on sea urchins was confirmed later by Blakeslee in 1922 while working with Datura (Jimson weed). The normal diploid chromosome number in Datura is 24 which form 12 pairs in meiosis. Some plants however have 25 chromosomes (designated trisomies today).
An interesting feature of the 25th chromosome is that it could be identical to any one of the 12 pairs so that Datura plants could be classified into 12 types. Blakeslee found that the shape and size of the fruit capsule was different in all the 12 groups of plants.
This proved that the 12 chromosomes differed from each other qualitatively and each produced a morphologically different capsule. The work of Boveri and Sutton provided excellent correlation between Mendelian factors and chromosomes and became known as the Sutton-Boveri theory.
Their experiment led to the discovery of the following characteristic features of chromosomes:
(a) Continuity of chromosomes from one cell division to the next,
(b) Qualitative differences between individual chromosomes,
(c) Pairing of maternal with paternal chromosomes,
(d) Segregation of chromosomes at random i.e. independent assortment of chromosomes.
Sutton in 1903 found that the number of factors obeying Mendel’s law were more than the number of chromosome pairs in the cell. This means that there were many genes on a single chromosome and Mendel’s law of independent assortment could not be applied to them (due to phenomenon of linkage).
T.H. Morgan in 1909 showed that in Drosophila the gene for white eye colour was linked to the sex chromosome. He crossed a white-eyed male fly with normal red-eyed female and obtained an F1 progeny of red-eyed flies only.
The F1 red-eyed flies when mated amongst themselves produced F2 progeny in the ratio of 3 red to 1 white. But the striking feature was that all the F2 white-eyed flies were males. In this way Morgan demonstrated that the gene for eye colour was present on the X-chromosome.
The following year he showed that the genes for yellow body colour and for miniature wings were also carried on the X-chromosome. By performing dihybrid crosses (involving eye pigment and body colour) he could show that crossing over could change positions of linked genes (incomplete linkage).
C.B. Bridges, a student of Morgan provided support to the chromosome theory from his studies on non-disjunction. When a white-eyed female is crossed with a red-eyed male, normally the F1 consists of red-eyed females and white eyed males. Bridges found that some-times red-eyed males and white-eyed females were also present.
He found a cytological explanation by which the two X-chromosomes failed to separate at Metaphase I of meiosis. Thus both Xs passed together into 50 per cent of resulting eggs; the remaining 50 per cent of eggs did not receive an X-chromosome, a phenomenon known as primary non-disjunction.
If an egg with two X-chromosomes is fertilised by a normal Y carrying sperm, the resulting zygote has XXY chromosome constitution and is female. Bridges could demonstrate cytologically that such a female indeed had XXY chromosomes thus establishing the validity of the chromosome theory of inheritance.