Chromosomes in space and time

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The genetic material that makes up each chromosome of a higher organism is not haphazardly distributed throughout the cell nucleus, but is neatly packed into spatially distinct ‘chromosome territories’. Whether chromosome territories are arranged in particular patterns within the nucleus, and if so, whether such patterns are functionally relevant, has been controversial. An evolutionary study on the nuclear arrangement of chromosome territories now provides strong support for non-random chromosome localization and its functional importance in mammals.A striking example of a non-random arrangement of chromosomes is that of human chromosomes 18 and 19. Chromosome 18 is one of the most gene-poor human chromosomes, but chromosome 19 is one of the most gene-rich. Chromosome 18 is found preferentially at the periphery of the nucleus, whereas chromosome 19 is usually found towards the nuclear center. This correlation between gene density and preferential internal positioning holds true for the entire set of human chromosomes. From this observation one might predict that if positioning of chromosomes is of functional importance for an organism, chromosome locations might be maintained during evolution.Cremer and colleagues [1xEvolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Tanabe, H et al. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 3329–4424Crossref | Scopus (233)See all References][1] have now tested this prediction by comparing the nuclear position of chromosomes 18 and 19 in higher primates ranging from humans to the squirrel monkey, which is evolutionarily separated from humans by about 30 million years. In all species, the genetic material from chromosome 18 was at the periphery of the nucleus and chromosome 19 material was more centrally located. These results are all the more remarkable because chromosomes undergo rearrangements during evolution. For example, the genetic material corresponding to human chromosome 19 is found on three separate chromosomes in gibbon. Nevertheless, these regions behaved like human chromosome 19 material and they clustered in a central position in the interior of the nucleus.Evolutionary conservation of chromosome arrangements strongly supports a functional role for chromosome positioning. One possibility is the silencing of genes by association with heterochromatin, which is often more prevalent in the nuclear periphery. Another possibility is that groups of genes cluster within the nucleus to form nuclear neighborhoods, which are optimized for their gene expression and regulatory needs. Whatever the function of non-random chromosome arrangements, clearly the most intriguing questions are how these patterns are established and maintained, and what happens when they are disrupted, for example by translocations in cancer cells.