cytoplasmic incompatibility

CI was first reported in mosquitoes in the 1930s{{Cite book| publisher = Trustees of the British Museum| last = Marshall| first = John Frederick| title = The British Mosquitoes| date = 1938}} and then studied extensively in the 1950s by Sabbas Ghelelovitch{{Cite journal| volume = 234| issue = 24| pages = 2386–2388| last = Ghelelovitch| first = S.| title = Sur le determinisme génétique de la stérilitée dans le croisement entre differentes souches de Culex autogenicus Roubaud| journal = Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences| date = 1952}} and especially Hannes Laven. Laven apparently was also the first to recognise the potential for CI-induced speciation{{Cite journal| doi = 10.1101/SQB.1959.024.01.017| issn = 0091-7451| volume = 24| pages = 166–173| last = Laven| first = Hannes| title = Speciation by Cytoplasmic Isolation in the Culex Pipiens-Complex| journal = Cold Spring Harbor Symposia on Quantitative Biology| accessdate = 2023-11-01| date = 1959-01-01| url = http://symposium.cshlp.org/content/24/166| pmid = 14414640}} and population control.{{Cite journal| doi = 10.1038/216383a0| issn = 1476-4687| volume = 216| issue = 5113| pages = 383–384| last = Laven| first = H.| title = Eradication of Culex pipiens fatigans through Cytoplasmic Incompatibility| journal = Nature| accessdate = 2023-11-01| date = October 1967| pmid = 4228275| bibcode = 1967Natur.216..383L| s2cid = 36662629| url = https://www.nature.com/articles/216383a0}} The first mathematical model uncovering the population biological principles of CI was presented in 1959.{{cite journal | last=Caspari | first=Ernst | last2=Watson | first2=G. S. | title=On the Evolutionary Importance of Cytoplasmic Sterility in Mosquitoes | journal=Evolution | publisher=Oxford University Press (OUP) | volume=13 | issue=4 | year=1959 | issn=0014-3820 | doi=10.2307/2406138 | page=568}} In 1971, Janice Yen and A. Ralph Barr demonstrated the etiologic relationship between Wolbachia infection and cytoplasmic incompatibility in Culex mosquitos when they found that eggs were killed when the sperm of Wolbachia-infected males fertilized infection-free eggs.{{Cite journal |last1=Yen |first1=J. H. |last2=Barr |first2=A. R. |year=1971 |title=New hypothesis of the cause of cytoplasmic incompatibility in Culex pipiens |journal=Nature |volume=232 |pages=657–658 |doi=10.1038/232657a0 |pmid=4937405 |issue=5313|bibcode=1971Natur.232..657Y |s2cid=4146003 }} The discovery that Wolbachia is very common and widely distributed across arthropods{{Cite journal| doi = 10.1098/rspb.1995.0196| volume = 262| issue = 1364| pages = 197–204| last1 = Werren| first1 = John H.| last2 = Windsor| first2 = Donald| last3 = Guo| first3 = Li Rong| title = Distribution of Wolbachia among neotropical arthropods| journal = Proceedings of the Royal Society of London. Series B: Biological Sciences| accessdate = 2023-11-01| date = January 1997| s2cid = 86540721| url = https://royalsocietypublishing.org/doi/10.1098/rspb.1995.0196}}{{Cite journal| doi = 10.1098/rspb.2000.1139| issn = 0962-8452| volume = 267| issue = 1450| pages = 1277–1285| last1 = Werren| first1 = John H.| last2 = Windsor| first2 = Donald M.| title = Wolbachia infection frequencies in insects: evidence of a global equilibrium?| journal = Proceedings of the Royal Society of London. Series B: Biological Sciences| date = 2000-07-07| pmid = 10972121| pmc = 1690679}} lead to a surge in research on CI in the 1990s and 2000s. Several landmark studies in the 2010s{{Cite journal| doi = 10.1126/science.1162418| volume = 322| issue = 5902| pages = 702| last1 = Hedges| first1 = Lauren M.| last2 = Brownlie| first2 = Jeremy C.| last3 = O'Neill| first3 = Scott L.| last4 = Johnson| first4 = Karyn N.| title = Wolbachia and Virus Protection in Insects| journal = Science| accessdate = 2023-11-01| date = 2008-10-31| pmid = 18974344| bibcode = 2008Sci...322..702H| s2cid = 206514799| url = https://www.science.org/doi/full/10.1126/science.1162418}}{{Cite journal| doi = 10.1016/j.cell.2009.11.042| issn = 0092-8674| volume = 139| issue = 7| pages = 1268–1278| last1 = Moreira| first1 = Luciano A.| last2 = Iturbe-Ormaetxe| first2 = Iñaki| last3 = Jeffery| first3 = Jason A.| last4 = Lu| first4 = Guangjin| last5 = Pyke| first5 = Alyssa T.| last6 = Hedges| first6 = Lauren M.| last7 = Rocha| first7 = Bruno C.| last8 = Hall-Mendelin| first8 = Sonja| last9 = Day| first9 = Andrew| last10 = Riegler| first10 = Markus| last11 = Hugo| first11 = Leon E.| last12 = Johnson| first12 = Karyn N.| last13 = Kay| first13 = Brian H.| last14 = McGraw| first14 = Elizabeth A.| last15 = Hurk| first15 = Andrew F. van den| last16 = Ryan| first16 = Peter A.| last17 = O'Neill| first17 = Scott L.| title = A Wolbachia Symbiont in Aedes aegypti Limits Infection with Dengue, Chikungunya, and Plasmodium| journal = Cell| accessdate = 2023-11-01| date = 2009-12-24| url = https://www.cell.com/cell/abstract/S0092-8674(09)01500-1| pmid = 20064373| s2cid = 2018937| doi-access = free}}{{Cite journal| doi = 10.1371/journal.pbio.1000002| issn = 1545-7885| volume = 6| issue = 12| pages = –1000002| last1 = Teixeira| first1 = Luís| last2 = Ferreira| first2 = Álvaro| last3 = Ashburner| first3 = Michael| title = The Bacterial Symbiont Wolbachia Induces Resistance to RNA Viral Infections in Drosophila melanogaster| journal = PLOS Biology| date = 2008-12-23| pmid = 19222304| pmc = 2605931| doi-access = free}} paved the way to use CI-inducing Wolbachia for controlling suppressing diseases such as dengue fever in mosquitoes.{{Cite journal| volume = 476| issue = 7361| pages = 454–457| last1 = Hoffmann| first1 = Ary A.| display-authors=etal | title = Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission| journal = Nature| accessdate = 2023-11-01| date = 2011| doi = 10.1038/nature10356| pmid = 21866160| bibcode = 2011Natur.476..454H| s2cid = 4316652| url = https://www.nature.com/articles/nature10356}}

[[Image:Uni bidirectional ci.png|thumb|right|500px|Unidirectional CI: Mating of infected males and uninfected females results in CI. All other crosses are compatible.

Bidirectional CI: Mating of males infected with Wolbachia strain I and females infected by Wolbachia strain II (and vice versa) results in CI. ]]

CI occurs when a Wolbachia infected male mates with a female that is infected by another Wolbachia strain (bidirectional CI) or is uninfected (unidirectional CI).

Any other combination of un-/infected male/female crosses are compatible. An infected female is compatible with any uninfected male, or with any male infected with the same Wolbachia strain. On the other hand, an uninfected female is only compatible with an uninfected male. In other words, if the male is infected by a CI-inducing strain of Wolbachia that is non-existent in its mate, it is an incompatible cross. Turelli et al. 2018 finds that CI can be resolved by infection of the females with the same strain that is affecting the males, which imposes a population level incentive in favour of CI-inducing strains of Wolbachia. They also find that this propagates the WO phage.{{cite journal | last1=Kirsch | first1=Joshua M. | last2=Brzozowski | first2=Robert S. | last3=Faith | first3=Dominick | last4=Round | first4=June L. | last5=Secor | first5=Patrick R. | last6=Duerkop | first6=Breck A. | title=Bacteriophage-Bacteria Interactions in the Gut: From Invertebrates to Mammals | journal=Annual Review of Virology | publisher=Annual Reviews | volume=8 | issue=1 | date=2021-09-29 | issn=2327-056X | pmid=34255542| doi=10.1146/annurev-virology-091919-101238| pmc=8484061 | pages=95–113}} Hosts can be cured from Wolbachia infection by antibiotic use.

In diploid organisms CI leads to embryonic mortality. In contrast, CI in haplodiploid hosts can also manifest as embryonic mortality, but may also in some species lead to haploid offspring that then develop into males. The closely related species of the wasp Nasonia show embryonic mortality as well as male development among incompatible crosses. In N. vitripennis, however, the vast majority of the CI embryos are converted into males.Tram, U, Fredrick, K, Werren, J, Sullivan, W (2006). "Paternal chromosome segregation during the first mitotic division determines Wolbachia-induced cytoplasmic incompatibility phenotype", J. Cell Sci. 119, 10.1242/jcs.03095. http://jcs.biologists.org/cgi/content/abstract/119/17/3655

There are two distinguished events that lead to the CI inducing manipulation. The first occurs inside the Wolbachia infected male during spermatogenesis and is called modification. Because Wolbachia are absent from mature sperm and appear to be excluded during the individualization process, the modification must occur before the conclusion of spermatogenesis.{{cite journal | last1 = Snook | first1 = R | last2 = Cleland | first2 = S | last3 = Wolfner | first3 = M |author-link3=Mariana Wolfner | last4 = Karr | first4 = T | year = 2000 | title = Offsetting Effects of Wolbachia Infection and Heat Shock on Sperm Production in Drosophila simulans: Analyses of Fecundity, Fertility and Accessory Gland Proteins | url = http://www.genetics.org/cgi/content/full/155/1/167 | journal = Genetics | volume = 155 | issue = 1| pages = 167–178 | doi = 10.1093/genetics/155.1.167 | pmid = 10790392 | pmc = 1461085 }}

The second event, called rescue, takes place inside the fertilized egg where Wolbachia presence prevents CI from occurring. As long as the Wolbachia strains in egg and sperm cells correspond, harmful effects cannot be observed on a cellular level.

A major consequence of CI is the delayed entry into mitosis of the male pronucleus. As a secondary consequence, stemming from this asynchrony, the paternal chromosomes do not properly condense and align on the metaphase plate during the first mitosis. As a consequence, only the maternal chromosome segregate normally, producing haploid embryos. The rescue of CI by infected eggs leads to the restoration of synchrony between the female and the male pronucleus.{{cite journal | last1 = Tram | first1 = U | last2 = Sullivan | first2 = W | year = 2002 | title = Role of delayed nuclear envelope breakdown and mitosis in Wolbachia-induced cytoplasmic incompability | journal = Science | volume = 296 | issue = 5570| pages = 1124–1126 | doi=10.1126/science.1070536 | pmid=12004132| bibcode = 2002Sci...296.1124T | citeseerx = 10.1.1.625.2871 | s2cid = 23831610 }}{{cite journal | last1 = Lassy | first1 = C | last2 = Karr | first2 = T | year = 1996 | title = Cytological analysis of fertilization and early embryonic development in incompatible crosses of Drosophila simulans | journal = Mechanisms of Development | volume = 57 | issue = 1| pages = 47–58 | doi=10.1016/0925-4773(96)00527-8| pmid = 8817452 | doi-access = free }}

The exact mechanisms of how Wolbachia perform modification and rescue are unknown. In Drosophila, the earliest effects caused by CI can already be observed during the sperm chromatin remodeling of the paternal chromosomes.{{cite journal | last1 = Landmann | first1 = F | last2 = Orsi | first2 = GA | last3 = Loppin | first3 = B | last4 = Sullivan | first4 = W | year = 2009 | title = Wolbachia-Mediated Cytoplasmic Incompatibility Is Associated with Impaired Histone Deposition in the Male Pronucleus | journal = PLOS Pathog | volume = 5 | issue = 3| page = e1000343 | doi = 10.1371/journal.ppat.1000343 | pmid = 19300496 | pmc = 2652114 | doi-access = free }} However, it was also observed that in other host species, the defects caused by CI only occur much later in development.{{cite journal | last1 = Duron | first1 = O | last2 = Weill | first2 = M | year = 2006 | title = Wolbachia infection influences the development of Culex pipiens embryo in incompatible crosses | journal = Heredity | volume = 96 | issue = 6| pages = 493–500 | doi = 10.1038/sj.hdy.6800831 | pmid=16639421| doi-access = free }}

CI is a manipulative phenotype that can lead to the rapid spread of the bacteria inducing it. CI results in the death of uninfected offspring and therefore the infected offspring benefit from reduced competition within the population. When the CI-inducing bacteria are rare in the population, there will be only few incompatible matings and selection (or drive) towards higher frequencies will only be weak. However, the more common the bacteria become, the stronger the selection and hence the faster their spread through the population (positive frequency-dependent selection). Unimpeded, the bacteria can therefore quickly reach infection frequencies of 100%.

However, a number of empirically well-documented factors can slow down or even prevent the spread of CI-inducing agents.{{cite journal | last=Stouthamer | first=R. | last2=Breeuwer | first2=J. A. J. | last3=Hurst | first3=G. D. D. | title=Wolbachia Pipientis: Microbial Manipulator of Arthropod Reproduction | journal=Annual Review of Microbiology | publisher=Annual Reviews | volume=53 | issue=1 | year=1999 | issn=0066-4227 | doi=10.1146/annurev.micro.53.1.71 | pages=71–102}} These include imperfect maternal transmission, reduced fitness of infected individuals, or incomplete CI. When maternal transmission is incomplete and/or infected females have a reduced fitness, an 'infection threshold' arises so that the bacteria spread from an initial frequency above this threshold but become extinct when their initial frequency is below the threshold.{{cite journal | last=Fine | first=Paul E.M. | title=On the dynamics of symbiote-dependent cytoplasmic incompatibility in culicine mosquitoes | journal=Journal of Invertebrate Pathology | publisher=Elsevier BV | volume=31 | issue=1 | year=1978 | issn=0022-2011 | doi=10.1016/0022-2011(78)90102-7 | pages=10–18}} The invasion threshold may be overcome through random genetic drift and therefore facilitated by small (at least locally) population sizes.

More complex scenarios than that of a simple host population have been explored through mathematical models, including models with more than one strain or species of maternally inherited bacteria,{{cite journal | last=Frank | first=Steven A. | title=Dynamics of Cytoplasmic Incompatability with Multiple Wolbachia Infections | journal=Journal of Theoretical Biology | publisher=Elsevier BV | volume=192 | issue=2 | year=1998 | issn=0022-5193 | doi=10.1006/jtbi.1998.0652 | pages=213–218}} structured host populations,{{cite journal | last=Engelstädter | first=J | last2=Telschow | first2=A | title=Cytoplasmic incompatibility and host population structure | journal=Heredity | publisher=Springer Science and Business Media LLC | volume=103 | issue=3 | date=2009-05-13 | issn=0018-067X | doi=10.1038/hdy.2009.53 | pages=196–207| doi-access=free }} random genetic drift{{cite journal | last=Jansen | first=Vincent A.A | last2=Turelli | first2=Michael | last3=Godfray | first3=H. Charles J | title=Stochastic spread of Wolbachia | journal=Proceedings of the Royal Society B: Biological Sciences | publisher=The Royal Society | volume=275 | issue=1652 | date=2008-08-26 | issn=0962-8452 | doi=10.1098/rspb.2008.0914 | pages=2769–2776| pmc=2605827 }} and overlapping generations.{{cite journal | last=Turelli | first=Michael | title=Cytoplasmic incompatibility in populations with overlapping generations | journal=Evolution | publisher=Wiley | volume=64 | issue=1 | year=2010 | issn=0014-3820 | doi=10.1111/j.1558-5646.2009.00822.x | pages=232–241| doi-access=free }}

CI, as described by Werren,{{cite journal | last1 = Werren | first1 = J | year = 1997 | title = Biology of Wolbachia | url = http://www.rochester.edu/college/bio/labs/WerrenLab/My%20Papers/1997_Wolbach_AnRevEnt.pdf | journal = Annual Review of Entomology | volume = 42 | pages = 587–609 | doi=10.1146/annurev.ento.42.1.587 | pmid=15012323}} results in selection pressure on uninfected males, as infected females can mate both with uninfected males and infected males, but uninfected females cannot mate with infected males. As Wolbachia are only transmitted by females, this mechanism promotes the spread of Wolbachia and therefore keeps Wolbachia from dying out because of incomplete transmission. This has led to discoveries in control of disease transmission by using Wolbachia to control the reproduction of a population by introducing Wolbachia-infected males.{{cite journal|last1=Zabalou|first1=Sofia|last2=Riegler|first2=Markus|last3=Theodorakopoulou|first3=Marianna|title=Wolbachia-induced cytoplasmic incompatibility as a means for insect pest population control|journal=Proceedings of the National Academy of Sciences of the United States of America|date=9 September 2004|volume=101|issue=42|pages=15042–15045|doi=10.1073/pnas.0403853101|pmid=15469918|pmc=524042|bibcode=2004PNAS..10115042Z|doi-access=free}} This has been seen in the Aedes, mosquito, family, in the Aedes albopictus and Aedes aegypti species.

It is speculated that CI can lead to "rapid speciation". When two populations of the same species are infected by two Wolbachia strains A and B, they might be bidirectionally incompatible and crosses between the two populations do not lead to viable offspring. Thus gene flow between these two populations is interrupted, leading to constant segregation in development and, finally, to speciation. The populations develop to a point where incompatibility would be maintained even in absence of Wolbachia.

• Wolbachia
• Cardinium
• Endosymbiont
• Intragenomic conflict

{{reflist}}

{{DEFAULTSORT:Cytoplasmic Incompatibility}}

Category:Reproductive system