The amount of DNA a cell must accommodate is huge even for organisms with genomes of modest sizes. For example, the typical E coli cell measures about 1 µm in diameter and 2 µm in length, yet it must accommodate a (circular) DNA molecule with a length of about 1,600 µm — enough to encircle it more than 400 times.
Eukaryotic cells face an even greater challenge — a human cell contains enough DNA to wrap around it more than 15,000 times. Somehow all this DNA must be efficiently packaged yet still remain accessible to the cellular machinery for both DNA replication and the transcription of specific genes. Clearly, DNA packaging is a challenging problem for all forms of life. Let&’s look at how prokaryotes accomplish the task of organising their DNA and then consider how eukaryotes address the same problem.
The genome of prokaryotes such as E coli was once thought to be a “naked” DNA molecule lacking any elaborate organisation and with only trivial amounts of protein associated with it. We now know that the organisation of the bacterial genome is more like the chromosomes of eukaryotes than previously realised.
Bacterial geneticists therefore refer to the structure that contains the main bacterial genome as the bacterial chromosome. It is typically a circular DNA molecule, containing some bound protein, which is localised in a special region of the cell called the nucleoid. The DNA of the bacterial chromosome is negatively super-coiled and folded into an extensive series of loops averaging about 20,000 bp in length. Because the two ends of each loop are anchored to structural components found within the nucleoid, the super-coiling of individual loops can be altered without influencing that of adjacent ones.
In addition to its chromosome, a bacterial cell may contain one or more plasmids, which are relatively small, circular molecules of DNA that carry genes both for their own replication and, often, for one or more cellular functions (usually non-essential ones). Most plasmids are super-coiled, giving them a condensed form. Although plasmids replicate autonomously, the process is usually in sufficient synchrony with the replication of the bacterial chromosome to ensure a roughly comparable number of plasmids from one generation to the next. In E coli cells, three classes of plasmids are recognised. F (fertility) factors are involved in the process of conjugation while R (resistance) factors carry genes that confer drug resistance on the bacterial cell. And col (colicinogeni) factors allow the bacterium to secrete colicins, compounds that kill other bacteria lacking the same. In addition, some strains of E coli contain cryptic plasmids, which have no known function.
Coming to eukaryotic cells, DNA packaging becomes more complicated. First, substantially larger amounts are involved — each chromosome contains a single, linear DNA molecule of an enormous size. Second, greater structural complexity is introduced by the association of eukaryotic DNA with larger amounts and numbers of proteins. When bound to such proteins, the DNA is converted into chromatin fibres measuring 10 to 30 nm in diameter, which are normally dispersed throughout the nucleus. At the time of cell division (and in a few other special situations), such fibres condense and fold into much larger, compact structures that become recognisable as individual chromosomes.
The proteins with the most important role in chromatin structure are the histones, a group of relatively small proteins whose high content of the amino acids, lysine and arginine, gives them a strong positive charge. The binding of histones to DNA, which is negatively charged, is therefore stabilised by ionic bonds. In most cells, the mass of histones in chromatin is approximately equal to the mass of DNA. Histones are divided into five main types, designated HI, H2A, H2B, H3 and H4.
Chromatin contains roughly equal numbers of H2A, H2B, H3 and H4 molecules, and about half that number of HI molecules. These proportions are remarkably constant among different kinds of eukaryotic cells, regardless of the type of cell or its physiological state. In addition to histones, chromatin also contains a diverse group of non-histone proteins that play a variety of enzymatic, structural, and regulatory roles.
(The writer is Associate Professor, Head, Department of Botany, Ananda Mohan College, Kolkata, and also Fellow, Botanical Society of Bengal, and can be contacted at [email protected])