Chromosomal Inversion

The major sources of variation in the eukaryotic genome are chromosomal breakages and reunions, leading to inversions and translocations. If two breaks occur in a chromosome and the excised fragment is rotated 180° before being reunited, then an inversion occurs. Three breaks in a chromosome can lead to an intrachromosomal translocation. In humans, both pericentric (the position of the centromere is changed) and paracentric (the position of the centromere is not changed) inversions occur in 1 to 2% of the population. Surprisingly often these gross chromosomal inversions do not have any phenotypic consequence (1). Most of these inversions are pericentric and involve nonrandom chromosomal breakpoints (Fig.   1). 

Figure 1. Chromosomal inversions. Those that change the position of the centromere are called pericentric inversions (a), and those that maintain the position of the centromere are called paracentric (b).

The polytene chromosomes of Drosophila are especially suited for studying gross chromosomal rearrangements. It has been shown that the evolution of distinct species of Drosophila was associated with the accumulation of many paracentric and pericentric inversions, so that on average two new inversions can be identified in each species (2). Comparison of the chromosomal banding patterns of humans with that of various apes also reveals that several chromosomes have undergone inversions leading to detectable differences (3). Inversions have also been well documented in plants and fungi. Nevertheless, inversions are an unwelcome occurrence for sexually reproducing organisms because of the consequence for meiosis. Chromosomal inversions cause homologous chromosomes to become locally heterozygous, which can create problems during the chromosomal alignment process that happens in meiotic prophase. This heterozygosity is normally overcome by the formation of an inversion loop, so that chromosomal alignment is maintained where possible. Inversions also create problems for the appropriate segregation of chromosomal material if crossovers occur within the inversion loop.

 In humans, fertility is reduced because paracentric inversion prevents appropriate chromosomal segregation when a crossover occurs within an inversion loop. The products of a paracentric inversion are an acentric fragment and a dicentric chromosome, which breaks during anaphase. Only the two chromatids that are not involved in the crossover remain normal. The embryos generated from gametes without the full complement of chromosomes are generally inviable. With pericentric inversions, the risk of producing an abnormal embryo is increased, depending on the origin of the gamete. The products of a pericentric inversion have gene duplications and deficiencies.

These duplications potentially lead to defective gametes. With male gametes, there is a 4% risk of abnormality, and with female gametes there is an 8% risk. This presumably reflects the greater contribution of the female gamete and the maternal chromosomes to early embryonic development. Comparable decreases in fertility are found in flowering plants. This leads to a strong evolutionary selection against chromosomal inversion (4).

References

1. D. S. Moorehead (1976) Am. J. Human. Genet. 28, 294–301. 

2. H. Carson (1983) Genetics 103, 465–489. 

3. J. J. Yunis and O. Drakash (1982) Science 215, 1525–1529. 

4. S. Wright (1977) Evolution and Genetics of Populations, Vol. 4: Variability within and among natural populations, University of Chicago Press, Chicago.