A third type of chromosome rearrangement is a chromosome inversion, in which a chromosome segment is inverted—turned 180 degrees (see Figure 6.4c). If a chromosome originally had segments AB•CDEFG, then chromosome AB•CFEDG represents an inversion that includes segments DEF. For an inversion to take place, the chromosome must break in two places. Inversions that do not include the centromere, such as AB•CFEDG, are termed paracentric inversions (para meaning “next to”), whereas inversions that include the centromere, such as ADC•BEFG, are termed pericentric inversions (peri meaning “around”).

Inversion heterozygotes are common in many organisms, including a number of plants, some species of Drosophila, mosquitoes, and grasshoppers. Inversions may have played an important role in human evolution: G-banding patterns reveal that several human chromosomes differ from those of chimpanzees by only a pericentric inversion (Figure 6.11).

EFFECTS OF INVERSIONS Individual organisms with inversions have neither lost nor gained any genetic material; only the order of the chromosome segment has been altered. Nevertheless, these mutations often have pronounced phenotypic effects. An inversion may break a gene into two parts, and one part may move to a new location and destroy the function of the gene in that location. Even when the chromosome breaks lie between genes, phenotypic effects may arise from the inverted gene order. Many genes are regulated in a position-dependent manner; if their positions are altered by an inversion, their expression may be altered, an outcome referred to as a position effect. For example, when an inversion moves a wild-type allele (that normally encodes red eyes) at the white locus in Drosophila to a chromosome region that contains highly condensed and inactive chromatin, the wild-type allele is not expressed in some cells, resulting in an eye consisting of red and white spots.

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INVERSIONS IN MEIOSIS When an individual is homozygous for a particular inversion, no special problems arise in meiosis, and the two homologous chromosomes can pair and separate normally. However, when an individual is heterozygous for an inversion, the gene order of the two homologs differs, and the homologous sequences can align and pair only if the two chromosomes form an inversion loop (Figure 6.12).

Individuals heterozygous for inversions also exhibit reduced recombination among genes located in the inverted region. The frequency of crossing over within the inversion is not actually diminished, but when crossing over does take place, the result is abnormal gametes that do not give rise to viable offspring, and thus no recombinant progeny are observed. Let’s see why this happens.

Figure 6.13 illustrates the results of crossing over within a paracentric inversion. The individual is heterozygous for an inversion (see Figure 6.13a), with one wild-type, nonmutated chromosome (AB•CDEFG) and one inverted chromosome (AB•EDCFG). In prophase I of meiosis, an inversion loop forms, allowing the homologous sequences to pair up (see Figure 6.13b). If a single crossover takes place in the inverted region (between segments C and D in Figure 6.13), an unusual structure results (see Figure 6.13c). The two outer chromatids, which did not participate in crossing over, contain original, nonrecombinant gene sequences. The two inner chromatids, which did participate in crossing over, are highly abnormal: each has two copies of some genes and no copies of others. Furthermore, one of the four chromatids now has two centromeres and is said to be a dicentric chromatid; the other lacks a centromere and is an acentric chromatid.

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In anaphase I of meiosis, the centromeres are pulled toward opposite poles and the two homologous chromosomes separate. This action stretches the dicentric chromatid across the center of the nucleus, forming a structure called a dicentric bridge (see Figure 6.13d). Eventually, the dicentric bridge breaks as the two centromeres are pulled farther apart. Spindle microtubules do not attach to the acentric fragment, so this fragment does not segregate to a spindle pole and is usually lost when the nucleus re-forms.

In the second division of meiosis, the chromatids separate and four gametes are produced (see Figure 6.13e). Two of the gametes contain the original, nonrecombinant chromosomes (AB•CDEFG and AB•EDCFG). The other two gametes contain recombinant chromosomes that are missing some genes; these gametes will not produce viable offspring. Thus, no recombinant progeny result when crossing over takes place within a paracentric inversion. The key is to recognize that crossing over still takes place, but when it does so, the resulting recombinant gametes are not viable, so no recombinant progeny are observed.

Recombination is also reduced within a pericentric inversion (Figure 6.14). No dicentric bridges or acentric fragments are produced, but the recombinant chromosomes have too many copies of some genes and no copies of others, so gametes that receive the recombinant chromosomes cannot produce viable progeny.

Figure 6.14 illustrates the results of single crossovers within inversions. Double crossovers in which both crossovers are on the same two strands (two-strand double crossovers) result in functional recombinant chromosomes (to see why functional gametes are produced by double crossovers, try drawing the results of a two-strand double crossover). Thus, even though the overall rate of recombination is reduced within an inversion, some viable recombinant progeny may still be produced through two-strand double crossovers. TRY PROBLEM 19

IMPORTANCE OF INVERSIONS IN EVOLUTION Inversions can also play important evolutionary roles by suppressing recombination among a set of genes. As we have seen, crossing over within an inversion in an individual heterozygous for a pericentric or paracentric inversion leads to unbalanced gametes and no recombinant progeny. This suppression of recombination allows particular combinations of alleles that function well together to remain intact, unshuffled by recombination.