Molecular characterization studies of the inversion breakpoints in species of the
Abstract
High rates of chromosomal rearrangements are remarkably abundant in Drosophila Fallén, 1832 (Insecta, Diptera) genus, highlighting the paracentric inversions. Since different species of this genus are paradigms for genetics, evolutionary, and population studies, polymorphism analyses for chromosomal inversions have provided basic knowledge for beautiful biological questions. Chromosomal inversions suppress meiotic recombination and thus, natural selection can act to preserve favorable gene complexes. Analyses of natural and laboratory populations show that these polymorphisms provide adaptive advantages to their carriers in relation to diverse factors, such as niche exploration and climatic factors. In addition, due to their monophyletic origin, they also serve as genetic markers for the construction of unrooted phylogenies. With the increasing domain of molecular techniques and genome sequencing, factors such as the reuse of breakpoints by different inversions and the mechanisms that give rise to these polymorphisms have been exploited with scientific refinement. These analyses show the presence of regions that are hot spots for breakpoints, fitting the fragile breakage chromosomal evolution model, as well as the involvement of transposition elements at the origin of chromosomal inversions.
Keywords
- chromosomal evolution
- chromosomal inversion
- polytene chromosomes
- staggered breaks
- transposable elements
1. Introduction
Structural chromosome rearrangements originate from chromosomal breaks at different sites, followed by reconstitution of these breaks in a distinct combination. They involve large quantities of genetic material at the cytological level and can be visualized under light microscopy.
The analysis of different rearrangements in the karyotype of the species of this genus was favored due to the presence of the polytene chromosomes. These polytene chromosomes are formed in interphase nuclei and are the final product of successive replication cycles without the consequent separation of the daughter chromatids, resulting in a huge structure that presents natural banding, formed by the precise synapses of parallel chromomeres of the sisters’ chromatids. It is estimated that the polytene chromosomes founded in the salivary glands undergo 210 replication events, generating up to 1024 filaments in each chromosomal pair of a diploid cell [1], originating a unique visualization magnitude. Tissues and organs containing cells with polytene chromosomes are, in general, involved in intense short time secretory functions, in a fast-growing context. Another peculiarity of the interphase polytene chromosomes is the non-segregation after replication; the parental chromosomes remain united and paired in the same conformation only seen in meiosis I of most other organisms [2].
The physical structure of the polytene chromosomes enables the accurate analysis of the different chromosomal rearrangements in
Inversions are classified in two types, in diploid organisms: paracentric (do not involve the centromere in its formation, occurring in the same chromosome arm) and pericentric (involve the centromere and more than one chromosome arm). This rearrangement can be visualized as heterozygous during the pairing of the homologous chromosomes in meiosis I when only one of the parental chromosomes carries the inversion, forming an inversion loop for the correct pairing of the homologous chromosomes; or as homozygous when both parental chromosomes carry the inversion. These chromosomal conformations can be visualized on the
Chromosomal inversions, compared to the other structural chromosomal rearrangements, use to be better tolerated by the organisms that carry them, since do not imply, theoretically, an increase or reduction of the genomic material. An inversion that occurs within a gene, however, can result in mutation, often lethal to the organism. The changing position of the genes, related to each other’s and their controlling sequences, which is called the position effect, is another consequence of the inversion, resulting in alterations of gene expression and, consequently, alterations at the phenotypic level.
The behavior of a heterozygous inversion and the consequences it may entail differs during meiosis and mitosis. In meiosis I, the occurrence of crossing over inside of a paracentric inversion loop induces the formation of a dicentric chromosome (with two centromeres) and an acentric fragment (without centromere), resulting in gametes with deletions. In contrast, the occurrence of a meiotic recombination at the pericentric inversion loop results in the normal segregation of the chromosomes during meiosis I, since the centromeres are contained in the inversion, but originates gametes with deletion and duplications at meiosis II ending. During the mitosis, a heterozygous inversion does not imply major difficulties for the course of the cycle, since each chromosome duplicates and the sister chromatids are directed to the resulting daughter cells [4]. Illustrations of this are found in several genetics books, usually in Structural Chromosomal Alterations chapter.
Species of the
There is a mechanism in the meiosis of females of
The mechanism of protection against the production of inviable gametes in males of
Aside from the inferred suppression of recombination in males, reports of its occurrence at the meiotic level are present in the literature, evidencing some peculiarities. Among these, the high occurrence in males showing the phenomenon of the hybrid dysgenesis of different species stands out. This phenomenon is also characterized by the presence of high frequencies of inviable offspring, mutations, structural chromosomal alterations, and distortion of the rate of transmission of alleles by one sex [9].
Another peculiarity is the spontaneous occurrence of recombination in males of species with a high degree of polymorphism for paracentric inversions, such as
Despite the exceptions, the presence of several cases of multiple heterozygosities occurring in many species of
2. Population studies of chromosomal inversions in the genus Drosophila
The high polymorphism of chromosomal inversions has been used as a model for different adaptative processes, involved in the maintenance of the genetic variation. The concerns of Theodosius Dobzhansky and collaborators, more than 80 years ago, originated the early studies encompassing analyses of chromosomal inversions in natural populations of
The work of Dobzhansky “Genetics and the Origin of Species” [14] was a great incentive to the development of experimentation in evolutionary and population genetics.
Several experiments with
The Neotropical species
Although several characteristics are indirectly associated with the inversions, little progress has been made in defining the genetic-evolutionary basis of these associations [23]. Direct shreds of evidence associating chromosomal inversions and selective pressures have been presented with the advancement of molecular techniques and genome sequencing.
Increasing amounts of data tend to confirm the inhibition of the recombination within the inversion area and also in adjacent areas, which is fundamental to the maintenance of the adaptive role. The patterns of linkage disequilibrium (LD) located within these regions reflect the inversion history and the gene flow since its origin [27, 28, 29, 30, 31].
An example of this case comes from the study of genetic variation and the unbalance of cosmopolitan inversion
Despite the confirmed association of chromosomal inversions with the maintenance of combinations of alleles that lie within this region, gene recombination in the inverted region of a chromosome is possible because viable recombinant gametes arise through double meiotic recombination within the inverted region and also in consequence of gene conversion [31].
The prediction of recombination rates analysis in chromosomes carrying a heterozygous inversion, based on two mathematical models (Poison and Couting), made by Navarro and collaborators [32] infer three main points about this: “(i) the lower the inversion, the greater the effect on the reduction of the double meiotic recombination rate; (ii) in short inversions and in regions around the breakpoint, inversion reduces the rate of recombination but does not have the same capacity to prevent gene conversion; (iii) reduction of the recombination rate is not uniform throughout the chromosome, generally reducing the gene flow between different arrangements to near zero close to the breakpoints, and higher recombination rates are found in the central regions of the inversion.” The inversion also influences the events of recombination of regions outside their limits. All these findings have implications for the analyses that use balancer chromosomes [32, 33, 34].
It should be noted that a fraction of these chromosomal polymorphisms occurring in the different species is adaptively neutral, and thus suffer less selective pressure (or none), and its fixation, or loss, depends on population size and migration. These inversions can also reach high frequencies through other mechanisms, such as the inversion
Despite the high acceptance and diffusion of the co-adaptation model of the genes contained in the inversions in
3. Inversions breakpoints in Drosophila : chromosomal distribution
Parallel to the evolutionary-population studies of chromosomal inversions in
Krimbas and Powel [37] wrote the best definition of the traditional point of view for the genesis of inversions: “It is that they are the result of two independent breaks, occurring at the same time, followed by the reconnection of the broken parts of the chromosome in an inverted orientation with respect to neighboring regions. Thus, the multiple overlapping inversions found in many
The monophyletic origin of the inversions implies that different rearrangements in the same chromosome can clarify some aspect of the evolutionary history of the analyzed species (or distinct species, when inter-crossings are possible), establishing the inversions as genetic markers for the reconstruction of unrooted phylogenies [39, 40].
“The first genetic dataset used for phylogenetic construction were the inversions of the chromosome 3 of
The analysis of the phylogenetic relationships of overlapping inversions [39] considers the most parsimonious route (those with the small amount of inversion) for the evolutionary inference. Phylogenies were constructed for various species groups, such as
Considering the traditional point of view of an inversion genesis, the distribution of the inversions along the chromosomes occurs randomly [37]. Sometimes, this characteristic seems to be well suited to the chromosomal distribution of the arrangement of chromosome 3 of
However, increasingly consistent studies evidencing the occurrence of repeated breaks in the same site for different inversions in a considerable amount of species have raised doubts regarding the randomness of the breakpoints distribution. These sites were denominated “hot spots,” and may involve particular structural instabilities of these regions [37].
The availability of the complete human genome and other mammals showed the effects of the limitations of the random breakage model, since it did not consider countless regions of the genomes of these organisms, because they were not available. The analysis of 281 syntenic blocks up to 1 Mb shared between humans and mouse showed the presence of 190 additional blocks with less than 1 Mb in size, which was very difficult to identify by alignment, and were totally unknown until then. The comparison of the chromosomal rearrangements occurred during the divergence between the two species showed a large number of breakpoints close to each other. This characteristic did not fit the random breakage model theory, so the fragile breakage model was proposed [53, 54].
This model was based on the inference that breakpoints of chromosome rearrangements occur mainly within fragile genome sites (hot spots), in other words, regions prone to breakage. These fragile sites may correspond to regions with lots of transposable elements (TEs), to segmental duplications, or to a palindromic sequence. “The reuse feature does not imply the use of the same genomic position (at the nucleotide level) repeatedly, but rather that, the breakpoint presents multiple genomic regions that originate chromosomal rearrangements [53, 54].”
Pioneering results at cytological level, on the reuse of breakpoints by different inversions, provided challenging data about the randomness of these breaks in
Although the reuse intra or interspecific of the inversions breakpoints, at cytological level, is common and well documented in the
4. Characterization of inversion breakpoints in Drosophila and origin mechanisms
Delimitation and characterization of the inversion breakpoints are fundamental to determinate the mechanisms that originate them. In
The first mechanism is the non-allelic homologous recombination (NAHR, also called ectopic recombination) between repetitive sequences, especially, the TEs [65, 66, 67]. The molecular machinery used by this mechanism is the same as allelic recombination, which has direct involvement with the genetic recombination in meiosis I. When ectopic recombination occurs between two copies of a repetitive sequence (very similar or identical), which are located physically at different chromosomal sites and in opposite orientations, the resulting inverted chromosome segment is flanked by two copies of these sequences, which are chimeric due to the exchange between them [66, 67]. The minimum identity between two sequences required for recombination is called minimal effective processing segment (MEPS). This parameter is not yet satisfactorily elucidated,
The second mechanism is via the erroneous repair of the free extremities, resulting from the chromosomal staggered breaks, by the non-homologous end joining (NHEJ). The physically close breaks in the chromosome cause failures in the correct pairing of the nitrogen bases, and the chromosomal regions separate. The inversion is due to the junction of the 5′ end with the 3′ end of the other breakpoint [60, 70]. Duplicated DNA segments and in opposite orientations (delimiting the inverted chromosome segment) are the result of the repair and the main recognition mark of this mechanism [59]. In Figure 3 it is possible to notice that staggered breaks occurred on both sides, duplicating two sequences that were originally single copies. However, based on the same figure, it is possible to extrapolate the occurrence of staggered breaks in only one side, and a simple break in the other side. The result is the duplication of just one originally single copy segment flanking the inversion. These duplicate sequences may involve genes. Gene duplication has been implicated as one of the main sources for the evolution of the genomes. The duplicate copy often does not undergo selective pressure, thus mutating more rapidly than the other essential regions of the genome. This may result in new gene functions, which is considered one of the most important results of these duplication events [71]. Thus, the repair of the free ends of staggered breaks by NHEJ gives rise to two different structural rearrangements: chromosomal inversion and duplication. Although in the case in question, duplications have small chromosomal magnitude compared to inversions, when they involve genes, they can also provide genomic variability in populations, and act on adaptive processes, speciation, and chromosome evolution.
The contribution of these two mechanisms is not completely clarified, and intriguing questions such as “whether these mechanisms are generalized among species of the genus and whether there are functional implications through the chromosomal evolution maintained by these inversions, remain open [59]”.
Table 1
presents a compilation of the different studies that characterized the inversion breakpoints at the molecular level in different species of the
Species | Chromosomal inversion | Breakpoints description and mechanism of chromosomal inversion genesis |
---|---|---|
|
|
Analysis by microdissection and sequencing of the inversion region in the chromosome. Absence of repetitive sequences at the breakpoints [72]. |
|
Fixed inversion in the X chromosome of |
Sequences of approximately 30–50 bp rich in thymines flanking the breakpoints [73]. |
|
|
Analysis of the proximal breakpoint and presence of a TE – LINE [74]. |
|
|
Presence of homologous copies of a TE denominated |
|
|
Presence of homologous copies of a TE denominated |
|
|
Presence of 128 and 315 bp repetitive motifs in opposite orientation at the breakpoints of the inversion. Origin of the inversion by NAHR between the inverted copies of these repetitions [75]. |
|
|
Small duplications in both breakpoints of the inversion [76]. |
|
29 inversions | 17 (59%) of the inversions presented inverted duplications at the breakpoints, including the |
|
|
Repetitive sequences in opposite orientation of a |
|
Inversion in the X chromosome | Absence of repetitive sequences at the breakpoints of the inversion [78]. |
|
Inversion in the X and II chromosomes |
|
|
|
Presence of homologous copies of the TE |
|
|
Absence of significant repetitive sequences at the breakpoints [80]. |
|
|
Absence of significant repetitive sequences at the breakpoints. Probable origin by single breaks [70]. |
|
Inversions |
Presence of copies of the |
|
Inversions |
|
|
Inversions |
Presence of inverted duplications at the breakpoints of the |
|
||
|
Inversions |
Presence of copies of the TE |
|
|
300 bp sequence in both breakpoints; origin of the inversion by staggered breaks [84]. |
|
Inversions |
Probable origin of the |
|
Inversions |
Presence of duplicated region (~8 Kbp) at the breakpoints of the |
|
|
Presence of the |
|
Inversions |
Duplications in both breakpoints of the inversions; origin by staggered breaks [87]. |
4.1. Involvement of the transposable elements at the origin of the inversions: non-allelic homologous recombination
Transposable elements are interesting and dominant components of the prokaryote and eukaryote genomes, meaning that the comprehension of their biology is a fundamental subject in genetics. Since their discovered by McClintock [88], much has been learned regarding the molecular properties of the TEs and their contribution to genome configuration of living beings.
These elements are classified according to their characteristics and transposition mode. Class I elements, also called retrotransposons, replicate through a “copy and paste” method and involve the production of an RNAm intermediary, processed by reverse transcription to DNA and re-inserted in the genome. The retrotransposons subdivide into elements with Long Terminal Repeats (LTRs), for example,
Class II elements, or DNA transposons, replicate, generically by a “cut and paste” mechanism, where the elements are physically excised from the genome and inserted into another site. In this case, there is an increase in the number of copies during the repairing of the excision sites of the DNA transposon by the host during DNA synthesis, or by the insertion of the TE in a genome site which has not been replicated [90, 91]. Still, among Class II elements, there is a non-autonomous element group denominated MITEs (Miniature Inverted-repeat Transposable Elements). These elements are short sequences with several copies in the genome and without coding capacity, as suggested by
The TEs of both classes are also classified in Subclass, Order, Superfamily, Family, and Subfamily based on their sharing of certain structures and sequence similarities [91].
The studies associating TEs with chromosomal rearrangements breakpoints in
The association of TEs insertions at cytological level with inversions breakpoints in natural populations of
The first analysis that directly evidenced the involvement of a TE at the origin of an inversion in a natural
Subsequently, the
Still, with respect to inversion
There are also analyses of fixed inversions
There is an extensive analysis of the mechanisms of origin of fixed inversions in
Another species that clearly presents the involvement of TEs in the genesis of their inversions is the
Subsequently, sequencing with low genome coverage of two strains of
4.2. Inversion origin via staggered breaks and repair by non-homologous end joining.
It has now been characterized that the origin of the inversions via staggered breaks followed by repair by NHEJ, is prevalent in two chromosomal systems: between the fixed chromosomal inversions that differentiate the
The study of Ranz et al. [59] analyzed the breakpoints of 29 interspecific inversions in these species through experimental and computational methods.
The analysis of the breakpoints of the
Due to the presence of inverted duplications associated with the
The same
The polymorphism of the Palearctic species
One of the pioneering analyzes in this species involved the characterization of the breakpoints of the
New probes were established via comparisons with the available genomes of
Still, in the O chromosome of
In the regions corresponding to the breakpoints of the
The
The
The extensive analysis done in the classical rearrangements of the E and O chromosomes, mentioned above, showed that, with the exception of the
Still considering staggered break mechanism followed by erroneous repair by NHEJ, the molecular characterization of the inversion breakpoints in
Staggered single-break occurred in the two breakpoints of the parental chromosome in the
The
5. Concluding remarks
Inversions are structural chromosomal alterations that, most of the time, neither imply genetic unbalance, nor phenotypic modifications in its carriers. However, one of its characteristics is to be a source of genetic variability, in which natural selection acts. Thus, the inversions participate in the chromosomal evolution of numerous species, including
The first works, with descriptive approaches to the frequency of chromosome polymorphism in different natural populations, while indirectly pointing out that the inversions provided advantages to its users, raised questions that until now guide the analysis on this theme: How does natural selection work in inversions? How do inversions offer greater adaptability to living beings? What is the role of the inversions in the speciation processes? What are the functional consequences of inversions in living beings? Are inversions randomly distributed on chromosomes? How do inversions originate?
The
The molecular characterization of the inversion breakpoints tells us about the mechanisms that originate these rearrangements, the genomic composition of the region involved in the inversion—which allows to analyze the nucleotide variation and to show which genes are under selection—the reuse of certain regions for the breakage of different inversions that occurred at different times, the age of the inversion, its monophyletic origin, possible positional effect and its influence on the genes that are inside and outside the inversion, among others. Valuable understandings emerge, but are still incipient.
These analyses go far from being simplistic, but, with the current resources, we have never had so much opportunity to acquire knowledge. Let us live the new time in science, and avail the most of the knowledge already established, with the certainty that many other questions will arise.
As the eminent geneticist Michael Ashburner of the University of Cambridge, United Kingdom, compiles: “What a wonderful time to be a biologist [105].”
Acknowledgments
We are grateful to Mr. Leonardo Lindenmeyer for all the assistance provided with the images of this manuscript. Grants and fellowships of Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, process 455101/2014-0) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) from Brazil.
References
- 1.
Swift H. Nucleic acids and cell morphology in dipteran salivary glands. In: Allen JM, editor. The Molecular Control of Cellular Activity. New York: McGraw Hill; 1962. pp. 73-125 - 2.
Zhimulev IF, Koryakov DE. Polytene chromosomes. Encyclopedia of Life Sciences (ELS). Chichester: John Wiley & Sons, Ltd; 2009. DOI: 10.1002/9780470015902.a0001183.pub2 - 3.
Hartl DL, Jones EW. Human karyotypes and chromosome behavior. In: Genetics: Analysis of Genes and Genomes. 7th ed. London: Jones and Bartlett; 2009. pp. 250-294 - 4.
Griffiths AJF, Wessler SR, Carroll SB, John Doebley J. Large-scale chromosomal changes. In: Introduction to Genetic Analysis. 9th ed. New York: WH Freeman & Company; 2015. pp. 481-520 - 5.
Powell JR. Population genetics—Inversions. In: Progress and Prospects in Evolutionary Biology—The Drosophila Model. New York: Oxford University; 1997. pp. 48-80 - 6.
Orr-Weaver TL. Meiosis in Drosophila : seeing is believing. Proceedings of the National Academy of Sciences of the United States of America. 1995;92 (23):10443-10449. PMCID: PMC40628 - 7.
Hinton CW, Lucchesi JC. A Cytogenetic study of crossing over in inversion heterozygotes of Drosophila melanogaster . Genetics. 1960;45 (1):87-94. PMCID: PMC1210005 - 8.
Morgan TH. Complete linkage in the second chromosome of the male of Drosophila . Science. 1912;36 (934):719-720. DOI: 10.1126/science.36.934.719 - 9.
Kidwell MG, Kidwell JF, Sved JA. Hybrid dysgenesis in Drosophila melanogaster : A syndrome of aberrant traits including mutation, sterility, and male recombination. Genetics. 1977;86 (4):813-833. PMCID: PMC1213713 - 10.
Henderson SA, Woodruff RC, Thompson JN. Spontaneous chromosome breakage at male meiosis associated with male recombination in Drosophila melanogaster . Genetics. 1978;88 (1):93-107. PMCID: PMC1213793 - 11.
Goñi B, Matsuda M, Yamamoto MT, Vilela CR, Tobari YN. Crossing over does occur in males of Drosophila ananassae from natural populations. Genome. 2012;55 (7):505-511. DOI: 10.1139/g2012-037 - 12.
Santos-Colares MC, Degrand TH, Valente VLS. Cytological detection of male recombination in Drosophila willistoni . Cytologia (Tokyo). 2004;69 (4):359-365. DOI: 10.1508/cytologia.69.359 - 13.
Dobzhansky T. Genetics of the Evolutionary Process. New York: Columbia University Press; 1970 - 14.
Dobzhansky T. Genetics and the Origin of Species. 1st, 2nd, 3rd ed. New York: Columbia University Press, 1937, 1941, 1951 - 15.
Dobzhansky T. On some of the problems of population genetics and evolution. Symposium sui Fattori Ecologici e Genetici della Speciazione Degli Animali. La Reserca Scientifica. 1949; 19 (Suppl):11 - 16.
Lambert DM, McLea MC. Drosophila pseudoobscura from New Zealand. Drosophila Information Service. 1983;59 :72-73 - 17.
Anderson WW, Arnold J, Baldwin DG, Beckenbach AT, Brown CJ, Bryant SH, Coyne JA, Harshman LG, Heed WB, Jeffery DE, et al. Four decades of inversion polymorphism in Drosophila pseudoobscura . Proceedings of the National Academy of Sciences of the United States of America. 1991;88 (22):10367-10371. PMCID: PMC52929 - 18.
Brncic D, Prevosti A, Budnik M, Monclús M, Ocaña J. Colonization of Drosophila subobscura in Chile I. First population and cytogenetic studies. Genetica. 1981;56 (1):3-9. DOI: 10.1007/BF00126923 - 19.
Balanyà J, Huey RB, Gilchrist GW, Serra L. The chromosomal polymorphism of Drosophila subobscura : A microevolutionary weapon to monitor global change. Heredity (Edinburgh). 2009;103 (5):364-367. DOI: 10.1038/hdy.2009.86 - 20.
Kenig B, Kurbalija Novičić Z, Patenković A, Stamenković-Radak M, Anđelković M. Adaptive role of inversion polymorphism of Drosophila subobscura in lead stressed environment. PLoS One. 2015;10 (6):e0131270. DOI: 10.1371/journal.pone.0131270 - 21.
Fontdevila A, Ruiz A, Ocaña J, Alonso G. Evolutionary history of Drosophila buzzatii . II. How much has chromosomal polymorphism changed in colonization? Evolution. 1982;36 (4):843-851. DOI: 10.1111/j.1558-5646.1982.tb05450.x - 22.
Hoffmann AA, Sgrò CM, Weeks AR. Chromosomal inversion polymorphisms and adaptation. Trends in Ecology & Evolution. 2004; 19 (9):482-488. DOI: 10.1016/j.tree.2004.06.013 - 23.
Schaeffer SW, Goetting-Minesky MP, Kovacevic M, Peoples JR, Graybill JL, et al. Evolutionary genomics of inversions in Drosophila pseudoobscura : Evidence for epistasis. Proceedings of the National Academy of Sciences of the United States of America. 2003;100 (14):8319-8324. DOI: 10.1073/pnas.1432900100 - 24.
Galina A, Peixoto AA, Bitner-Mathé CB, Souza WN, Silva LB, Valente VLS, Klaczko LB. Chromosomal inversion polymorphism in Drosophila mediopunctata : Seasonal, altitudinal, and latitudinal variation. Genetics and Molecular Biology. 2004;27 (1):61-69. DOI: 10.1590/S1415-47572004000100011 - 25.
Klaczko LB. Evolutionary genetics of Drosophila mediopunctata . Genetica. 2006;126 (1):43-55. DOI: 10.1007/s10709-005-1431-6 - 26.
Batista MR, Ananina G, Klaczko LB. Unexpected long-term changes in chromosome inversion frequencies in a Neotropical Drosophila species. Climate Research. 2012;53 (2):131-140. DOI: 10.3354/cr01088 - 27.
Pegueroles C, Ordóñez V, Mestres F, Pascual M. Recombination and selection in the maintenance of the adaptive value of inversions. Journal of Evolutionary Biology. 2010; 23 (12):2709-2717. DOI: 10.1111/j.1420-9101.2010.02136.x - 28.
McGaugh SE, Noor MA. Genomic impacts of chromosomal inversions in parapatric Drosophila species. Philosophical Transactions of the Royal Society B. 2012;367 (1587):422-429. DOI: 10.1098/rstb.2011.0250 - 29.
Fuller ZL, Haynes GD, Zhu D, Batterton M, Chao H, et al. Evidence for stabilizing selection on codon usage in chromosomal rearrangements of Drosophila pseudoobscura . G3 (Bethesda). 2014;4 (12):2433-2449. DOI: 10.1534/g3.114.014860 - 30.
Rane RV, Rako L, Kapun M, Lee SF, Hoffmann AA. Genomic evidence for role of inversion 3RP ofDrosophila melanogaster in facilitating climate change adaptation. Molecular Ecology. 2015;24 (10):2423-2432. DOI: 10.1111/mec.13161 - 31.
Chovnick A. Gene conversion and transfer of genetic information within the inverted region of inversion heterozygotes. Genetics. 1973; 75 (1):123-131. PMCID: PMC1212990 - 32.
Navarro A, Betran E, Barbadilla A, Ruiz A. Recombination and gene flux caused by gene conversion and crossing over in inversion heterokaryotypes. Genetics. 1997; 146 :695-709. PMCID: PMC1208008 - 33.
Andolfatto P, Depaulis F, Navarro A. Inversion polymorphisms and nucleotide variability in Drosophila . Genetical Research. 2001;77 (1):1-8. DOI: 10.1017/S0016672301004955 - 34.
Miller DE, Cook KR, Yeganeh Kazemi N, Smith CB, Cockrell AJ, Hawley RS, Bergman CM. Rare recombination events generate sequence diversity among balancer chromosomes in Drosophila melanogaster . Proceedings of the National Academy of Sciences of the United States of America. 2016;113 (10):E1352-E1361. DOI: 10.1073/pnas.1601232113 - 35.
Corbett-Detig RB, Hartl DL. Population genomics of inversion polymorphisms in Drosophila melanogaster . PLoS Genetics. 2012;8 (12):e1003056. DOI: 10.1371/journal.pgen.1003056 - 36.
Kirkpatrick M, Barton N. Chromosome inversions, local adaptation and speciation. Genetics. 2006; 173 (1):419-434. DOI: 10.1534/genetics.105.047985 - 37.
Krimbas CB, Powell JR. Chromosomal polymorphism in natural and experimental populations. In: Krimbas CB, Powell JR, editors. Drosophila Inversion Polymorphism. Florida, USA: CRC; 1982. pp. 2-52 - 38.
Sperlich D, Pfriem P. Chromosomal polymorphism in natural and experimental population. In: Ashburner M, Carson HL, Thompson JN Jr, editors. The Genetics and Biology of Drosophila . Vol. 3e. London: Academic Inc.; 1986. pp. 257-309 - 39.
Sturtevant AH, Dobzhansky T. Inversions in the third chromosome of wild races of Drosophila pseudoobscura , and their use in the study of the history of the species. Proceedings of the National Academy of Sciences of the United States of America. 1936;22 (7):448-450. PMCID: PMC1076803 - 40.
Dobzhansky T, Sturtevant AH. Inversions in the chromosomes of Drosophila pseudoobscura . Genetics. 1938;23 :28-64. PMCID: PMC1209001 - 41.
Wallace AG, Detweiler D, Schaeffer SW. Evolutionary history of the third chromosome gene arrangements of Drosophila pseudoobscura inferred from inversion breakpoints. Molecular Biology and Evolution. 2011;28 (8):2219-2229. DOI: 10.1093/molbev/msr039 - 42.
Lemeunier F, Aulard S. Inversion polymorphism in Drosophila melanogaster . In: Krimbas CB, Powell JR, editors. Drosophila Inversion Polymorphism. Florida, USA: CRC; 1982. pp. 339-405 - 43.
Heed WB, Russell JS. Phylogeny and population structure in island and continental species of the cardini group ofDrosophila studied by inversion analysis. University of Texas Publishing. 1971;7103 :91-130 - 44.
Carson HL, Kaneshiro KY. Drosophila of Hawaii: Systematics and ecological genetics. Annual Review of Ecological Systems. 1976;7 :311-345. DOI: 10.1146/annurev.es.07.110176.001523 - 45.
Throckmorton LH. The virilis species group. In: Ashburner M, Carson HL, Thompson JN, editors. The Genetics and Biology ofDrosophila . Vol. 3b. London: Academic Press; 1982. pp. 227-296 - 46.
Diniz NM, Sene FM. Chromosomal phylogeny of the Drosophila fasciola species subgroup revisited (Diptera, Drosophilidae). Genetics and Molecular Biology. 2004;27 (4):561-556. DOI: 10.1590/S1415-47572004000400016 - 47.
Rohde C, Garcia AC, Valiati VH, Valente VL. Chromosomal evolution of sibling species of the Drosophila willistoni group. I. Chromosomal arm IIR (Muller's element B). Genetica. 2006;126 (1-2):77-88. DOI: 10.1007/s10709-005-1433-4 - 48.
Olvera O, Powell JR, de la Rosa ME, Salceda VM, et al. Populations genetics of Mexican Drosophila . VI. Cytogenetics aspects of the inversion polymorphism inDrosophila pseudoobscura . Evolution. 1979;33 :381-395. DOI: 10.2307/2407628 - 49.
Jackson WD, Barber HN. Patterns of chromosome breakage after irradiation and ageing. Heredity. 1958; 12 :1-25. DOI: 10.1038/hdy.1958.1 - 50.
Ohno S. Ancient linkage groups and frozen accidents. Nature. 1973; 244 (5414):259-262. DOI: 10.1038/244259a0 - 51.
Sachs RK, Levy D, Chen AM, Simpson PJ, Cornforth MN, et al. Random breakage and reunion chromosome aberration formation model; an interaction-distance version based on chromatin geometry. International Journal of Radiation Biology. 2000; 76 (12):1579-1588. DOI: 10.1080/09553000050201064 - 52.
Nadeau JH, Taylor BA. Lengths of chromosomal segments conserved since divergence of man and mouse. Proceedings of the National Academy of Sciences of the United States of America. 1984; 81 :814-818. PMCID: PMC344928 - 53.
Pevzner P, Tesler G. Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution. Proceedings of the National Academy of Sciences of the United States of America. 2003; 100 (13):7672-7677. DOI: 10.1073/pnas.1330369100 - 54.
González J, Casals F, Ruiz A. Testing chromosomal phylogenies and inversion breakpoint reuse in Drosophila . Genetics. 2007;175 (1):167-177. DOI: 10.1534/genetics.106.062612 - 55.
Cáceres M, Barbadilla A, Ruiz A. Inversion length and breakpoint distribution in the Drosophila buzzatii species complex: Is inversion length a selected trait? Evolution. 1997;51 (4):1149-1155. DOI: 10.2307/2411044 - 56.
Krimbas CB, Loukas M. The inversion polymorphism of Drosophila subobscura . In: Hecht MK, Steere WC, Wallace B, editors. Evo biol. Vol. 12. New York: Plenum Press; 1980. pp. 163-234 - 57.
Tonzetich J, Lyttle TW, Carson HL. Induced and natural break sites in the chromosomes of Hawaiian Drosophila . Proceedings of the National Academy of Sciences of the United States of America. 1988;85 (5):1717-1721. PMCID: PMC279846 - 58.
Rohde C, Valente VLS. Three decades of studies on chromosomal polymorphism of Drosophila willistoni and description of fifty different rearrangements. Genetics and Molecular Biology. 2012;35 (4):966-979. DOI: 10.1590/S1415-47572012000600012 - 59.
Ranz JM, Maurin D, Chan YS, von Grotthuss M, Hillier LW, Roote J, et al. Principles of genome evolution in the Drosophila melanogaster species group. PLoS Biology. 2007;5 :1366-1381. DOI: 10.1371/journal.pbio.0050152 - 60.
Calvete O, González J, Betrán E, Ruiz A. Segmental duplication, microinversion, and gene loss associated with a complex inversion breakpoint region in Drosophila . Molecular Biology and Evolution. 2012;29 (7):1875-1889. DOI: 10.1093/molbev/mss067 - 61.
Puerma E, Orengo DJ, Salguero D, Papaceit M, Segarra C, Aguadé M. Characterization of the breakpoints of a polymorphic inversion complex detects strict and broad breakpoint reuse at the molecular level. Molecular Biology and Evolution. 2014; 31 (9):2331-2341. DOI: 10.1093/molbev/msu177 - 62.
Drosophila 12 Genomes Consortium. Evolution of genes and genomes on the Drosophila phylogeny. Nature. 2007;480 :203-218. DOI: 10.1038/nature06341 - 63.
Bhutkar A, Schaeffer SW, Russo SM, et al. Chromosomal rearrangement inferred from comparisons of 12 Drosophila genomes. Genetics. 2008;179 (3):1657-1680. DOI: 10.1534/genetics.107.086108 - 64.
von Grotthuss M, Ashburner M, Ranz JM. Fragile regions and not functional constraints predominate in shaping gene organization in the genus Drosophila . Genome Research. 2010;20 (8):1084-1096. DOI: 10.1101/gr.103713.109 - 65.
Cáceres M, Ranz JM, Barbadilla A, Long M, Ruiz A. Generation of a widespread Drosophila inversion by a transposable element. Science. 1999;285 :415-418. DOI: 10.1126/science.285.5426.415 - 66.
Casals F, Caceres M, Ruiz A. The foldback-like transposon Galileo is involved in the generation of two different natural chromosomal inversions ofDrosophila buzzatii . Molecular Biology and Evolution. 2003;20 :674-685. DOI: 10.1093/molbev/msg070 - 67.
Delprat A, Negre B, Puig M, Ruiz A. The transposon Galileo generates natural chromosomal inversions in Drosophila by ectopic recombination. PLoS One. 2009;4 :e7883. DOI: 10.1093/molbev/msg070 - 68.
Jinks-Robertson S, Michelitch M, Ramcharan S. Substrate length requirements for efficient mitotic recombination in Saccharomyces cerevisiae . Molecular and Cellular Biology. 1993;13 :3937-3950. DOI: 10.1128/MCB - 69.
Hoang ML, Tan FJ, Lai DC, Celniker SE, Hoskins RA, et al. Competitive repair by naturally dispersed repetitive DNA during non-allelic homologous recombination. PLoS Genetics. 2010; 6 (12):e1001228. DOI: 10.1371/journal.pgen.1001228 - 70.
Runcie DE, Noor MA. Sequence signatures of a recent chromosomal rearrangement in Drosophila mojavensis . Genetica. 2009;136 (1):5-11. DOI: 10.1007/s10709-008-9296-0 - 71.
Ohno S. Evolution by Gene Duplication. New York Inc.: Springer-Verlag; 1970. 160p - 72.
Wesley CS, Eanes WF. Isolation and analysis of the breakpoint sequences of chromosome inversion In(3L)Payne inDrosophila melanogaster . Proceedings of the National Academy of Sciences of the United States of America. 1994;91 (8):3132-3136. PMCID: PMC43529 - 73.
Cirera S, Martin-Campos JM, Segarra C, Aguade M. Molecular characterization of the breakpoints of an inversion fixed between Drosophila melanogaster andD. subobscura . Genetics. 1995;139 :321-326. PMCID: PM7705632 - 74.
Andolfatto P, Wall JD, Kreitman M. Unusual haplotype structure at the proximal breakpoint of In(2L)t in a natural population ofDrosophila melanogaster . Genetics. 1999;153 :1297-1311. PMCID: PM10545460 - 75.
Richards S, Liu Y, Bettencourt BR, Hradecky P, Letovsky PS, et al. Comparative genome sequencing of Drosophila pseudoobscura : Chromosomal, gene, and cis-element evolution. Genome Research. 2005;15 :1-18. DOI: 10.1101/gr.3059305 - 76.
Matzkin LM, Merritt TJ, Zhu CT, Eanes WF. The structure and population genetics of the breakpoints associated with the cosmopolitan chromosomal inversion In(3R)Payne inDrosophila melanogaster . Genetics. 2005;170 :1143-1152. DOI: 10.1534/genetics.104.038810 - 77.
Evans AL, Mena PA, McAllister BF. Positive selection near an inversion breakpoint on the neo-X chromosome of Drosophila americana . Genetics. 2007;177 (3):1303-1319. DOI: 10.1534/genetics.107.073932 - 78.
Cirulli ET, Noor MA. Localization and characterization of X chromosome inversion breakpoints separating Drosophila mojavensis andDrosophila arizonae . The Journal of Heredity. 2007;98 (2):111-114. DOI: 10.1093/jhered/esl065 - 79.
Machado CA, Haselkorn TS, Noor MA. Evaluation of the genomic extent of effects of fixed inversion differences on intraspecific variation and interspecific gene flow in Drosophila pseudoobscura andD. persimilis . Genetics. 2007;175 (3):1289-1306. DOI: 10.1534/genetics.106.064758 - 80.
Prazeres da Costa O, González J, Ruiz A. Cloning and sequencing of the breakpoint regions of inversion 5g fixed inDrosophila buzzatii . Chromosoma. 2009;118 (3):349-360. DOI: 10.1007/s00412-008-0201-5 - 81.
Fonseca NA, Vieira CP, Schlötterer C, Vieira J. The DAIBAM MITE element is involved in the origin of one fixed and two polymorphicDrosophila virilis phylad inversions. Fly (Austin). 2012;6 (2):71-74. DOI: 10.4161/fly.19423 - 82.
Corbett-Detig RB, Cardeno C, Langley CH. Sequence-based detection and breakpoint assembly of polymorphic inversions. Genetics. 2012; 192 :131-137. DOI: 10.1534/genetics.112.141622 - 83.
Guillén Y, Ruiz A. Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution. BMC Genomics. 2012;13 (1):53. DOI: 10.1186/1471-2164-13-53 - 84.
Papaceit M, Segarra C, Aguadé M. Structure and population genetics of the breakpoints of a polymorphic inversion in Drosophila subobscura . Evolution. 2012;67 :66-79. DOI: 10.1111/j.1558-5646.2012.01731.x - 85.
Orengo DJ, Puerma E, Papaceit M, Segarra C, Aguadé MA. Molecular perspective on a complex polymorphic inversion system with cytological evidence of multiply reused breakpoints. Heredity (Edinburgh). 2015; 114 (6):610-618. DOI: 10.1038/hdy.2015 - 86.
Puerma E, Orengo DJ, Aguadé M. The origin of chromosomal inversions as a source of segmental duplications in the Sophophora subgenus ofDrosophila . Scientific Reports. 2016;6 :30715. DOI: 10.1038/srep30715 - 87.
Puerma E, Orengo DJ, Aguadé M. Multiple and diverse structural changes affect the breakpoint regions of polymorphic inversions across the Drosophila genus. Scientific Reports. 2016;6 :36248. DOI: 10.1038/srep36248 - 88.
McClintock B. Maize genetics. Carnegie Institution of Washington Year Book. 1946; 45 :176-186 - 89.
Capy P. Classification and nomenclature of retrotransposable elements. Cytogenetic and Genome Research. 2005; 110 (1-4):457-461. DOI: 10.1159/000084978 - 90.
Finnegan DJ. Eukaryotic transposable elements and genome evolution. Trends in Genetics. 1989; 5 :103-107. DOI: 10.1016/0168-9525(89)90039-5 - 91.
Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, et al. A unified classification system for eukaryotic transposable elements. Nature Reviews. Genetics. 2007; 8 (12):973-982. DOI: 10.1038/nrg2165 - 92.
Deprá M, Ludwig A, Valente VLS, Loreto ELS. Mar, a MITE family of hAT transposons in Drosophila . Mobile DNA. 2012;3 :13. DOI: 10.1186/1759-8753-3-13 - 93.
Kidwell MG. Transposable elements and the evolution of dipteran genomes. In: Yeates DK, Wiegmann BM, editors. The Evolutionary Biology of Flies. New York: Columbia University; 2005. pp. 145-173 - 94.
Zelentsova H, Shostak N, Kozitsina M, Barskyi V, et al. Penelope , a new family of transposable elements and its possible role in hybrid dysgenesis inDrosophila virilis . Proceedings of the National Academy of Sciences of the United States of America. 1997;94 (1):196-201. PMCID: PMC19282 - 95.
Engels WR, Preston CR. Formation of chromosome rearrangements by P factors inDrosophila . Genetics. 1984;107 :657-678. PMCID: PMC1202383 - 96.
Lyttle TW, Haymer DS. The role of the transposable element hobo in the origin of endemic inversions in wild populations ofDrosophila melanogaster . Genetica. 1992;86 :113-126. DOI: 10.1007/BF00133715 - 97.
Regner LP, Pereira MSO, Alonso CEV, Abdelhay E, Valente VLS. Genomic distribution of P elements inDrosophila willistoni and a search for their relationship with chromosomal inversions. The Journal of Heredity. 1996;87 :191-198. DOI: 10.1093/oxfordjournals.jhered.a022984 - 98.
Zelentsova H, Poluectova H, Mnjoian L, Lyozin G, Veleikodvorskaja V, et al. Distribution and evolution of mobile elements in the virilis species group ofDrosophila . Chromosoma. 1999;108 (7):443-456. DOI: 10.1007/s004120050396 - 99.
Evgen'ev M, Zelentsova H, Mnjoian L, Poluectova H, Kidwell MG. Invasion of Drosophila virilis by the Penelope transposable element. Chromosoma. 2000;109 (5):350-357. DOI: 10.1007/s004120000086 - 100.
Marzo M, Puig M, Ruiz A. The Foldback-like elementGalileo belongs to theP superfamily of DNA transposons and is widespread within theDrosophila genus. Proceedings of the National Academy of Sciences of the United States of America. 2008;105 (8):2957-2962. DOI: 10.1073/pnas.0712110105 - 101.
Puig M, Cáceres M, Ruiz A. Silencing of a gene adjacent to the breakpoint of a widespread Drosophila inversion by a transposon-induced antisense RNA. Proceedings of the National Academy of Sciences of the United States of America. 2004;101 (24):9013-9018. DOI: 10.1073/pnas.0403090101 - 102.
González J, Nefedov M, Bosdet I, Casals F, Calvete O, et al. A BAC-based physical map of the Drosophila buzzatii genome. Genome Research. 2005;15 :885-892. DOI: 10.1101/gr.3263105 - 103.
Ruiz A, Heed WB, Wasserman M. Evolution of the mojavensis cluster of cactophilicDrosophila with descriptions of two new species. The Journal of Heredity. 1990;81 (1):30-42. DOI: 10.1093/oxfordjournals.jhered.a110922 - 104.
Sturtevant AH, Plunkett CR. Sequence of corresponding third chromosome genes in Drosophila melanogaster andDrosophila simulans . The Biological Bulletin. 1926;50 :56-60. DOI: 10.2307/1536631 - 105.
Ashburner M. Drosophila Genomes by the Baker’s Dozen. Genetics. 2007;177 (3):1263-1268. PMCID: PMC2147995