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Title:   Author  item
                                            KHAN, ASIS - Washington University School Of Medicineitem
                                            SHAIK, JAHANGHEER - Washington University School Of Medicineitem
                                            BEHNKE, MICHAEL - Washington University School Of Medicineitem
                                            WANG, QIULING - Washington University School Of Medicineitem
                                            Dubey, Jitenderitem
                                            LORENZI, HERNAN - J Craig Venter Instituteitem
                                            AJIOKA, JAMES - University Of Cambridgeitem
                                            Rosenthal, Benjaminitem
                                            SIBLEY, L - Washington University School Of Medicine
  Submitted to: BMC Genomics
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 9/9/2014
                                    Publication  Date: 12/16/2014
                                    Publication URL: http://doi:10.1186/1471-2164-15-1168Citation: Khan, A., Shaik, J.S., Behnke, M., Wang, Q., Dubey, J.P., Lorenzi, H.A., Ajioka, J.W., Rosenthal, B.M., Sibley, L.D. 2014. NextGen sequencing reveals short double crossovers contribute disproportionately to genetic diversity in Toxoplasma gondii. Biomed Central (BMC) Genomics. 15:1168.Interpretive Summary: Toxoplasma gondii is a widespread protozoan parasite of animals that causes zoonotic disease in humans.  Three clonal variants predominate in North America and Europe, while South American strains are genetically diverse, and undergo more frequent recombination.  All three northern clonal variants share a particular version of one chromosome. To understand its inheritance, we performed a genetic cross between dissimilar parasite types.  At first glance, the chromosome appeared to recombine, because the progeny appeared exactly like one or the other parent without genetic admixture.  Upon more fine-scale inspection, however, we detected a surprisingly great number of short regions reflecting the other parent’s genotype.  Another surprise entailed the inability of one of the parents to fertilze itself, instead requiring certain defined regions of the other strain to produce progeny in domesticated cats.  These findings suggested that the global spread of a particular form of this parasite likely stems from a fitness advantage, perhaps owing to specific genetic regions that enable the parasite to disseminate in domesticated cats.
                                Technical Abstract: Toxoplasma gondii is a widespread protozoan parasite of animals that causes zoonotic disease in humans.  Three clonal variants predominate in North America and Europe, while South American strains are genetically diverse, and undergo more frequent recombination.  All three northern clonal variants share a monomorphic version of chromosome Ia (ChrIa), which is also found in unrelated, but successful southern lineages.  To understand the inheritance of ChrIa, we performed a genetic cross between the northern clonal type 2 ME49 strain and a divergent southern type 10 strain called VAND, which harbors a divergent ChrIa.NextGen sequencing of haploid F1 progeny was used to generate a genetic map revealing a low level of conventional recombination, with an unexpectedly high frequency of short, double crossovers.  Notably, both the monomorphic and divergent versions of ChrIa were isolated with equal frequency.  As well, ChrIa showed no evidence of being a sex chromosome, of harboring an inversion, or affecting segregation.  Although VAND was unable to self fertilize in the cat, it underwent successful out-crossing with ME49 and hybrid survival was strongly associated with inheritance of ChrIII and ChrVIIa from ME49. Our findings predict that the successful spread of ChrIa in the wild is not due to meiotic drive or related processes but rather likely due to a fitness advantage.  As well, the high frequency of short double crossovers is expected to greatly increase genetic diversity among progeny from genetic crosses, thereby providing an unexpected and likely important source of diversity.


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