Chromosomal Duplication

There are numerous types of chromosomal duplications. Each chromosome itself is duplicated during the S-phase of the normal cell cycle. There are also various duplications that arise from chromosome breakage and reunion cycles, which might be an important contributory factor in the evolution of genomes. There are also duplication events that encompass whole genomes. In the frog Xenopus laevis, different species have evolved that contain multiple sets of related chromosomes. This is called polyploidy. Xenopus tropicalis is the progenitor diploid species, whereas Xenopus laevis is pseudotetraploid (1). Although many duplicated genes are silenced, genes that remain active often show tissue or developmental differences in activity. Thus specialized gene family members may arise by both genomic duplication and by genetic duplication. Other examples of chromosomal duplication result from gene amplification.

Chromosomal duplication occurs through a variety of mechanisms, some that operate in evolutionary time, and others that occur in specialized cells during development or in response to environmental stress. The most common form of chromosomal duplication results from unequal sister chromatid exchange. This is caused by misalignment of two sister chromatids during prophase followed by reciprocal recombination, which duplicates one chromosome, whereas the other has a deficiency. Amplification of the large 18 S and 28 S ribosomal RNA genes in Drosophila melanogaster might occur through many reiterations of events of this type (2). It is also possible that the presence of thousands of short interspersed nuclear elements, such as Alu repeats or the long interspersed nuclear element (LINE)-1 in mammalian chromosomes, might lead to many misalignments and chromosomal duplications.

 Gene amplification is another form of local chromosomal duplication. In cultured cells, treatment with methotrexate and hydroxyurea results in multiple replicative cycles of the dihydrofolate reductase (DHFR) gene. The molecular mechanisms controlling this overreplication of the DHFR gene are not understood, but it is assumed that the replicative process leads to the generation of free

DNA ends that then undergo homologous recombination (3). If the over-replicated DNA circularizes, double minute chromosomes are formed.

Chromosome duplication also occurs following modification of chromosomeal behavior during the cell cycle. Normally the DNA in chromosomes replicates once during S phase. If multiple replicative cycles occur, however, then duplicated chromosomes can coexist in the same somatic cell nucleus. If the chromosomes separate, the cell is called endopolyploid. If the chromosomes do not separate, polytene chromosomes are formed. This repeated replicative process is called endoreduplication (4). Endopolyploid cells and those containing polytene chromosomes never divide, so they represent, a somatic dead end or a state of terminal differentiation, respectively.

References

1.H. R. Kobel and L. Du Pasquier (1986) Trends Genet. 2, 310–313. 

2. S. A. Endow and K. C. Atwood (1988) Trends Genet. 4, 348–351. 

3. R. T. Schimke (1988) J. Biol. Chem. 263, 5989–5992. 

4. W. Nagl (1978) Endopolyploidy and Polyteny in Differentiation and Evolution, Elsevier/North Holland, Amsterdam.