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Mechanistic basis of infertility of mouse intersubspecific hybrids.

Bhattacharyya, T; Gregorova, S; Mihola, O; Anger, M; Sebestova, J; Denny, P; Simecek, P; (2013) Mechanistic basis of infertility of mouse intersubspecific hybrids. Proc Natl Acad Sci U S A , 110 (6) E468-E477. 10.1073/pnas.1219126110.

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Abstract

According to the Dobzhansky-Muller model, hybrid sterility is a consequence of the independent evolution of related taxa resulting in incompatible genomic interactions of their hybrids. The model implies that the incompatibilities evolve randomly, unless a particular gene or nongenic sequence diverges much faster than the rest of the genome. Here we propose that asynapsis of heterospecific chromosomes in meiotic prophase provides a recurrently evolving trigger for the meiotic arrest of interspecific F1 hybrids. We observed extensive asynapsis of chromosomes and disturbance of the sex body in >95% of pachynemas of Mus m. musculus × Mus m. domesticus sterile F1 males. Asynapsis was not preceded by a failure of double-strand break induction, and the rate of meiotic crossing over was not affected in synapsed chromosomes. DNA double-strand break repair was delayed or failed in unsynapsed autosomes, and misexpression of chromosome X and chromosome Y genes was detected in single pachynemas and by genome-wide expression profiling. Oocytes of F1 hybrid females showed the same kind of synaptic problems but with the incidence reduced to half. Most of the oocytes with pachytene asynapsis were eliminated before birth. We propose the heterospecific pairing of homologous chromosomes as a preexisting condition of asynapsis in interspecific hybrids. The asynapsis may represent a universal mechanistic basis of F1 hybrid sterility manifested by pachytene arrest. It is tempting to speculate that a fast-evolving subset of the noncoding genomic sequence important for chromosome pairing and synapsis may be the culprit.

Type: Article
Title: Mechanistic basis of infertility of mouse intersubspecific hybrids.
Location: United States
DOI: 10.1073/pnas.1219126110
Keywords: Animals, Apoptosis, Biological Evolution, Chromosome Pairing, Crosses, Genetic, DNA Breaks, Double-Stranded, Female, Genetic Speciation, Infertility, Male, Meiosis, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred Strains, Models, Biological, Oocytes, Pregnancy, Recombination, Genetic, Species Specificity, Spermatocytes, Spermatogenesis, Transcriptome
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Centre for Cardiovascular Genetics
URI: http://discovery.ucl.ac.uk/id/eprint/1459642
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