human chromosome

Chromosomes are organized structures of DNA and proteins that are found in cells. Chromosomes contain a single continuous piece of DNA, which contains many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. The word chromosome comes from the Greek χρῶμα (chroma, color) and σῶμα (soma, body) due to their property of being stained very strongly by some dyes.

Chromosomes vary extensively between different organisms. The DNA molecule may be circular or linear, and can contain anything from tens of kilobase pairs to hundreds of megabase pairs. Typically eukaryotic cells (cells with nuclei) have large linear chromosomes and prokaryotic cells (cells without nuclei) smaller circular chromosomes, although there are many exceptions to this rule. Furthermore, cells may contain more than one type of chromosome; for example mitochondria in most eukaryotes and chloroplasts in plants have their own small chromosomes.

In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called chromatin. This allows the massively-long DNA molecules to fit into the cell nucleus. The structure of chromatin varies through the cell cycle, and is responsible for the organisation of chromosomes into the classic four-arm structure during mitosis and meiosis.

"Chromosome" is a rather loosely defined term. In prokaryotes, a small circular DNA molecule may be called either a plasmid or a small chromosome. These small circular genomes are also found in mitochondria and chloroplasts, reflecting their bacterial origins. The simplest chromosomes are found in viruses: these DNA or RNA molecules are short linear or circular chromosomes that often lack any structural proteins.

his is a brief history of research in a complex field where each advance was hard won, and often hotly disputed at the time.

Visual discovery of chromosomes. Textbooks have often said that chromosomes were first observed in plant cells by a Swiss botanist named Karl Wilhelm von Nägeli in 1842.^[1] However, this opinion has been challenged, perhaps decisively, by Henry Harris, who has freshly reviewed the primary literature.^[2] In his opinion the claim of Nägeli to have seen spore mother cells divide is mistaken, as are some of his interpretations. Harris considers other candidates, especially Wilhelm Hofmeister, whose publications in 1848-9 include plates which definitely show mitotic events.^[3][4] Hofmeister was also the choice of Cyril Darlington.

The work of other cytologists such as Walther Flemming, Eduard Strasburger, Otto Bütschli, Oskar Hertwig and Carl Rabl should definitely be acknowledged. The use of basophilic aniline dyes was a new technique for effectively staining the chromatin material in the nucleus. Their behavior in animal (salamander) cells was later described in detail by Walther Flemming, who in 1882 "provided a superb summary of the state of the field".^[5][6] The name chromosome was invented in 1888 by Heinrich von Waldeyer. However, van Beneden's monograph of 1883 on the fertilised eggs of the parasitic roundworm Ascaris maglocephala was the outstanding work of this period.^[7] His conclusions are classic:

• Thus there is no fusion between the male chromatin and the female chromatin at any stage of division...
• The elements of male origin and those of female origin are never fused together in a cleavage nucleus, and perhaps they remain distinct in all the nuclei derived from them. [tranl: Harris p162]

"It is not easy to identify who first discerned chromosomes during mitosis, but there is no doubt that those who first saw them had no idea of their significance... [but] with the work of Balbiani and van Beneden we move away from... the mechanism of cell division to a precise delineation of chromosomes and what they do during the division of the cell." ^[8]

Van Beneden's master work was closely followed by that of Carl Rabl, who reached similar conclusions. ^[9] This more or less concludes the first period, in which chromosomes were visually sighted, and the morphological stages of mitosis were described. Coleman also gives a useful review of these discoveries.^[10]

Nucleus as the seat of heredity. The origin of this epoch-making idea lies in a few sentences tucked away in Ernst Haeckel's Generelle Morphologie of 1866.^[11] The evidence for this insight gradually acumulated until, after twenty or so years, two of the greatest in a line of great German scientists spelt it out. August Weismann proposed that the germ line was separate from the soma, and that the cell nucleus was the repository of the hereditary material, which he proposed was arranged along the chromosomes in a linear manner. Furthermore, he proposed that at fertilisation a new ombination of chromosomes (and their hereditary material) would be formed. This was the explanation for the reduction division of meiosis (first described by van Beneden).

Chromosomes as vectors of heredity. In a series of outstanding experiments, Theodor Boveri gave the definitive demonstration that chromosomes were the vectors of heredity. His two principles were:

The continuity of chromosomes

The individuality of chromosomes.

It was the second of these principles which was so original. He was able to test the proposal put forward by Wilhelm Roux, that each chromosome carries a different genetic load, and showed that Roux was right. Upon the rediscovery of Mendel, Boveri was able to point out the connection between the rules of inheritance and the behaviour of the chromosomes. It is interesting to see that Boveri influenced two generations of American cytologists: Edmund Beecher Wilson, Walter Sutton and Theophilus Painter were all influenced by Boveri (Wilson and Painter actually worked with him). In his famous textbook The Cell, Wilson linked Boveri and Sutton together by the Boveri-Sutton theory. Mayr remarks that the theory was hotly contested by some famous geneticists: William Bateson, Wilhelm Johannsen, Richard Goldschmidt and T.H. Morgan, all of a rather dogmatic turn of mind. Eventually complete proof came from chromosome maps – in Morgan's own lab!