Chromosomes are generally decondensed during interphase, so that the details of their structure are difficult to visualize. Notable exceptions are the specialized lampbrush chromosomes of vertebrate oocytes and the polytene chromosomes in the giant secretory cells of insects. Studies of these two types of interphase chromosomes suggest that each long DNA molecule in a chromosome is divided into a large number of discrete domains organized as loops of chromatin that are compacted by further folding. When genes contained in a loop are expressed, the loop unfolds and allows the cell’s machinery access to the DNA.
Interphase chromosomes occupy discrete territories in the cell nucleus; that is, they are not extensively intertwined. Euchromatin makes up most of interphase chromosomes and, when not being transcribed, it probably exists as tightly folded fibers of compacted nucleosomes. However, euchromatin is interrupted by stretches of heterochromatin, in which the nucleosomes are subjected to additional packing that usually renders the DNA resistant to gene expression. Heterochromatin exists in several forms, some of which are found in large blocks in and around centromeres and near telomeres. But heterochromatin is also present at many other positions on chromosomes, where it can serve to help regulate developmentally important genes.
The interior of the nucleus is highly dynamic, with heterochromatin often positioned near the nuclear envelope and loops of chromatin moving away from their chromosome territory when genes are very highly expressed. This reflects the existence of nuclear subcompartments, where different sets of biochemical reactions are facilitated by an increased concentration of selected proteins and RNAs. The components involved in forming a subcompartment can self-assemble into discrete organelles such as nucleoli or Cajal bodies; they can also be tethered to fixed structures such as the nuclear envelope.
During mitosis, gene expression shuts down and all chromosomes adopt a highly condensed conformation in a process that begins early in M phase to package the two DNA molecules of each replicated chromosome as two separately folded chromatids. The condensation is accompanied by histone modifications that facilitate chromatin packing, but satisfactory completion of this orderly process, which reduces the end-to-end distance of each DNA molecule from its interphase length by an additional factor of ten, requires additional proteins.
In this final section of the chapter, we provide an overview of some of the ways that genes and genomes have evolved over time to produce the vast diversity of modern-day life-forms on our planet. The sequencing of the genomes of thousands of organisms is revolutionizing our view of the process of evolution, uncovering an astonishing wealth of information about not only family relationships among organisms, but also about the molecular mechanisms by which evolution has proceeded.
It is perhaps not surprising that genes with similar functions can be found in a diverse range of living things. But the great revelation of the past 30 years has been the extent to which the actual nucleotide sequences of many genes have been conserved. Homologous genes—that is, genes that are similar in both their nucleotide sequence and function because of a common ancestry—can often be recognized across vast phylogenetic distances. Unmistakable homologs of many human genes are present in organisms as diverse as nematode worms, fruit flies, yeasts, and even bacteria. In many cases, the resemblance is so close that, for example, the protein-coding portion of a yeast gene can be substituted with its human homolog—even though humans and yeast are separated by more than a billion years of evolutionary history.
As emphasized in Chapter 3, the recognition of sequence similarity has become a major tool for inferring gene and protein function. Although a sequence match does not guarantee similarity in function, it has proved to be an excellent clue. Thus, it is often possible to predict the function of genes in humans for which no biochemical or genetic information is available simply by comparing their nucleotide sequences with the sequences of genes that have been characterized in other more readily studied organisms.