Chromosomal inversion

Aninversionis achromosome rearrangementin which a segment of a chromosome becomes inverted within its original position. An inversion occurs when achromosomeundergoes a two breaks within the chromosomal arm, and the segment between the two breaks inserts itself in the opposite direction in the same chromosome arm. The breakpoints of inversions often happen in regions of repetitive nucleotides, and the regions may be reused in other inversions.Chromosomal segments in inversions can be as small as 1 kilobases or as large as 100 megabases.The number of genes captured by an inversion can range from a handful of genes to hundreds of genes.Inversions can happen either throughectopic recombinationbetweenrepetitive sequences,or through chromosomal breakage followed bynon-homologous end joining.

Inversions are of two types:paracentricandpericentric.Paracentric inversions do not include thecentromere,and both breakpoints occur in one arm of the chromosome. Pericentric inversions span the centromere, and there is a breakpoint in each arm.

A clay model showing why heterozygous inversion loops are visible inpolytene chromosomepreparations

An inversion loop in the A arm of a chromosome from anAxarusspecies midge

Inversions usually do not cause any abnormalities in carriers, as long as the rearrangement is balanced, with no extra or missing DNA. However, in individuals which areheterozygousfor an inversion, there is an increased production of abnormalchromatids(this occurs when crossing-over occurs within the span of the inversion). This leads to lowered fertility, due to production of unbalanced gametes. Inversions do not involve either loss or gain of genetic information; they simply rearrange the linear DNA sequence.

Detection

Cytogenetictechniques may be able to detect inversions, or inversions may be inferred fromgenetic analysis.Nevertheless, in most species, small inversions go undetected. More recently, comparative genomics has been used to detect chromosomal inversions, by mapping the genome.Population genomics may also be used to detect inversions, using areas of highlinkage disequilibriumas indicators for possible inversion sites. Human families that may be carriers of inversions may be offeredgenetic counselingandgenetic testing.

History

The first evidence of a chromosomal inversion was found in 1921 byAlfred SturtevantinDrosophila melanogaster.Since then, inversions have been found in a alleukaryotes.When discovered by Sturtevant, inversions were regarded as areas of recombination suppression.

Originally, these inversions were noted inpolytene chromosomeswithin the salivary glands of heterozygousDrosophila melanogasterlarvae.In 1970,Theodosius Dobzhanskynoted that genes within an inversion had higher fitness than those that are found outside of the inversions, although this is an area that needs further study.

One of the more recent models of inversions is the Kirkpatrick and Barton Model (2006), which states that inversions are selectively advantageous by linking together adaptive alleles. By physically linking co-adapted variants at multiple genes into distinct versions (haplotypes) of an inversion, selection should be more efficient in driving these variants to high frequency in a population. This is in contrast to non-inverted regions, which may allow adaptive and maladaptive alleles to be carried.

Effects on recombination

When an inversion carrying chromosome is paired with a non-inverted homologous chromosome (Inversion heterozygotes) duringmeiosis,they fail to synapse properly and inversion loops are formed. Acrossing-overwithin the loop can produce unbalancedgametes.In a paracentric inversion,recombinationresults in one dicentricchromatidand one acentric chromatid. DuringAnaphase,both recombinants are faced with problems. The acentric chromatid is pulled to one pole or the other, and the dicentric recombinant generates dicentric bridges as it is pulled in two directions.

In a pericentric inversion, similar imbalanced chromosomes are produced. The recombinant chromosomes resulting from these crosses includedeletionsandduplications.The offspring produced by such gametes are mostly inviable, and therefore, recombination is indirectly suppressed within inverted regions.

Evolutionary consequences

The suppressed recombination between inversion heterozygotes provides an opportunity for the independent evolution of the ancestral and inverted arrangements. At the beginning, the inverted arrangement lacks variation, while the ancestral one does not. If the invertedhaplotypeis not lost (e.g. due todrift), the variation in the inverted arrangement can increase over time, and recombination rate in the inverted region is somewhat restored as more homozygotes are introduced.

Chromosomal inversions have gained a lot of attention in evolutionary research due to their potential role in local adaptation and speciation. Because non-recombining inversion haplotypes may harbor multiple co-adapted gene variants, inversions are thought to facilitate local adaptation to different environments because natural selection is more efficient in driving such linked adaptive variants to high frequency within a population.However, empirically demonstrating the presence of linked, co-adapted gene variants within inversions is difficult because inversion haplotypes do not recombine. Moreover, this possible positive effect of chromosomal inversions for adaptation to different environments rests on the assumption that adaptive gene variants linked into distinct inversion haplotypes are indeed co-adapted. This idea is, however, likely violated in situations where populations experience spatially or temporally varying selection. Because of fluctuating selection on inversion-linked variants, the absence of recombination between inversion haplotypes harboring distinct gene variants may then constrain rather than help adaptation to distinct environments.The importance of chromosomal inversions in adaptation to different environments therefore remains an open empirical problem in evolutionary genetics.

Inversion polymorphism can be established in two ways. Genetic drift or selection can result infixationof an inversion in a local population. Inversion polymorphism can result fromgene flowbetween this population and a population without the inversion.Balancing selectioncan also result in inversion polymorphism by frequency dependence oroverdominance.Thefitnessdifferences between the inverted and the ancestral chromosome can either produce a stable polymorphism or can result in the fixation of one or the other chromosome.

Inversions have been essential tosex chromosomeevolution. In mammals, the Y chromosome is unable to recombine with the X chromosome, almost along its entire length. This non-recombining portion results from a series of inversions that overlap. Decreased recombination rate between sex determininglociand sex-anatagonistic genes is favored by selection. This causes linkage disequilibrium between the male determining locus and analleleat another locus that is beneficial to males. This can happen through inversions resulting in a non-recombining block including both loci, as is the case in the mammalian Y chromosome.

Inversions can also be essential in the origination of new sex chromosomes. They can cause linkage disequilibrium between a sex-determining mutation and sex-antagonistic loci and create a new sex chromosome from an autosome.

Inversions can be involved inspeciationin multiple ways. Since heterozygote inversions can beunderdominant,they can cause hybrid fitness loss, resulting inpost-zygotic isolation.They can also accumulate selected differences between species, causing both pre- and post-zygotic isolation.

Inversions often form geographical clines in frequency which can hint to their role in local adaptation. A prominent instance of such a cline is inversion 3RP inDrosophila melanogasterthat can be observed in three different continents.When an inversion contains two or more locally adaptive alleles, it can be selected and spread. For example; in the butterflyHeliconius numata,18 genes controlling colors are linked together by inversions as together they confer higher fitness.

Nomenclature

Three chromosomal abnormalities with ISCN nomenclature, with increasing complexity:(A)A tumour karyotype in a male with loss of the Y chromosome,(B)Prader–Willi Syndrome i.e. deletion in the 15q11-q12 region and(C)an arbitrary karyotype that involves a variety of autosomal and allosomal abnormalities including inversions (abbreviated asinv).

Humankaryotypewith annotated bands and sub-bands as used for the nomenclature of chromosome abnormalities. It shows dark and white regions as seen onG banding.Each row is vertically aligned atcentromerelevel. It shows 22homologousautosomalchromosome pairs as well as both the female (XX) and male (XY) versions of the twosex chromosomes.

Further information:Karyotype

TheInternational System for Human Cytogenomic Nomenclature(ISCN) is an international standard forhuman chromosomenomenclature,which includes band names, symbols, and abbreviated terms used in the description of human chromosome and chromosome abnormalities. Abbreviations includeinvfor inversions.

Notable cases

• Brenden Adams: former holder of theGuinness World Recordfor tallest teenager. His height is caused by an inversion ofchromosome 12.
• An example of chromosomal Inversion in organisms is demonstrated in the insect,Coelopa frigida.This particular species ofCoelopahave a variation of chromosomal inversions that allow the species to create a series of physical differences. IndividualC. frigidathat are larger do not undergo a chromosomal inversion, whereas individuals that are smaller do undergo a chromosomal inversion.

Further reading

• Lehtonen S, Myllys L, Huttunen S (2009)."Phylogenetic analysis of non-coding plastid DNAthtjtdjj in the presence of short inversions"(PDF-preview).Phytotaxa.1:3–20.doi:10.11646/phytotaxa.1.1.2.