The following points highlight the top four models proposed for chromosome structure. The models are: 1. Molecular Model 2. Multi-Stranded Model or Polyneme Chromosome Model 3. General Chromosome Model 4. Folded Fibre Model.

Chromosome Structure: Model # 1. Molecular Model:

This model of chromosome structure was proposed by Taylor and coworkers in 1957, 1963 and is based on the semiconservative replication of eukaryotic chromosome. According to this model, the chromatid consists of only one DNA chain, where several DNA double helices linked end-to-end by protein molecules.

Interactions of protein molecules with each other are responsible for coiling and uncoiling of the chromosomes. DNA molecule can be broken by deoxyribonucleases but not by proteolytic enzymes.

Chromosome Structure: Model # 2. Multi-Stranded Model or Polyneme Chromosome Model:

This model was put forth by Ris in 1961 and Ris and Chandler in 1963. According to this model, the chromosome is multi-stranded, i.e., it contains several DNA double helices arranged parallel to each other. Each chromosome is divided into two chromatids, each chromatid is made of two “half chromatids” and each half chromatid is composed of two “quarter chromatids.”

Each “quarter chromatid” is, in turn, made of four chromatin fibres and each chromatin fibre contains 2 DNA double helices. The diameter of the DNA double helix is 2 nm, and two DNA molecules are associated with protein to make the chromatin fibre.

Diameters of chromatin fibres, quarter chromatids, half chromatids and chromatids are 10 nm, 40 nm, 80 nm, and 160 nm, respectively. Thus each chromatid contains 32 DNA molecules, while the metaphase chromosome contains 64 DNA molecules. However, according to the recent studies, the chromosome is definitely not multi-stranded.

Chromosome Structure: Model # 3. General Chromosome Model:

This model was proposed by Crick in 1971; it suggests that DNA in a chromatid is a large monomer which runs continuously from one end to the other. Band and inter band regions of chromosomes (especially giant chromosomes) are suggested to have distinct functions. The bands contain globular control DNA, while the inter-bands contain fibrous coding DNA.

Chromosome Structure: Model # 4. Folded Fibre Model:

DuPraw in 1965 proposed this model on the basis of electron microscopic studies of human chromosomes. According to this model, each chromatid contains single long nucleoprotein complex (Chromatin fibres) in which a single DNA double helix forms the main structure of the axis. This model of chromosome has been widely accepted.

The main features of this model are as follows:

(1) Before interphase replication, each chromosome consists of a single chromatid made up of a single 200-500 A thick chromatin fibre; each fibre contains a single long DNA double helix which is associated with proteins and RNA.

(2) The chromatin fibre (chromatid) replicates during S phase of call cycle to produce two sister chromatids which are held together by the un-replicated regions.

(3) This pair of sister chromatids folds up to form a visible chromosome at prophase, but sister chromatids are held together by minute un-replicated regions.

(4) Exact folding and packing patterns of chromatids of different chromosomes are thought to vary in some specific ways.

Thus each metaphase chromatid is composed of tightly folded single chromatin fibre of 200-500 A diameter. The exact 3-dimensional configuration of nucleoprotein fibre in any given chromatid is not constant. This configuration varies from metaphase to interphase.

It also differs for the same chromosome during mitosis and meiosis, in mature sperm, and from metaphase to metaphase. Non-homologous chromosomes differ not only in their genetic content but also in their 3-dimensional configurations.

This model suggests that in the centromeric region, chromatin fibres are continuous and pass from one arm to the other for each sister chromatid; the sister chromatids are held closely together in this region up to the beginning of their separation during anaphase. This model also suggests that a small amount of DNA is synthesized before the sister chromatids actually separate. The diagrammatic representation of the folded fibre model is given in the Fig. 8.2.

The chromatin fibres are proposed to be of “A” and “B” type. The A type fibre is intermediate between the extended DNA double helix and the fully packed B type fibre. DNA double helix is 20 A in diameter; it associates with histones to form a nucleohistone fibril.

Chromosome Replication and Structure

This fibril folds into a super-helix of 100 A diameter with a pitch of 120 Å; this is the type A fibre. The 100 A fibril folds under the influence of divalent cations (Ca2+, Mg2+) to give rise to a branched system of 250 Å fibres.

The fully packed fibre is 200-500 Å in diameter and is called a B type fibre. When Ca2+ and Mg2+ are removed, the 200-500 A fibres unfold into 100 A fibrils. The digestion of 100 A fibrils by proteinase enzymes releases a single 20-30 Å thick stand (DNA double helix) which is susceptible to DNAase.