Age and Genetic Background Modify Hybrid Male Sterility in House Mice

Hybrid male sterility (HMS) contributes to reproductive isolation commonly observed among house mouse (Mus musculus) subspecies, both in the wild and in laboratory crosses. Incompatibilities involving specific Prdm9 alleles and certain Chromosome (Chr) X genotypes are known determinants of fertility and HMS, and previous work in the field has demonstrated that genetic background modifies these two major loci. We constructed hybrids that have identical genotypes at Prdm9 and identical X chromosomes, but differ widely across the rest of the genome. In each case, we crossed female PWK/PhJ mice representative of the M. m. musculus subspecies to males from a classical inbred strain representative of M. m. domesticus: 129S1/SvImJ, A/J, C57BL/6J, or DBA/2J. We detected three distinct trajectories of fertility among the hybrids using breeding experiments. The PWK129S1 males were always infertile. PWKDBA2 males were fertile, despite their genotypes at the major HMS loci. We also observed age-dependent changes in fertility parameters across multiple genetic backgrounds. The PWKB6 and PWKAJ males were always infertile before 12 weeks and after 35 weeks. However, some PWKB6 and PWKAJ males were transiently fertile between 12 and 35 weeks. This observation could resolve previous contradictory reports about the fertility of PWKB6. Taken together, these results point to multiple segregating HMS modifier alleles, some of which have age-related modes of action. The ultimate identification of these alleles and their age-related mechanisms will advance understanding both of the genetic architecture of HMS and of how reproductive barriers are maintained between house mouse subspecies.

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Age and genetic background modify hybrid male sterility in house mice

10.1101/2020.06.26.173047 ◽

2020 ◽

Author(s):

Samuel J. Widmayer ◽

Mary Ann Handel ◽

David L. Aylor

Keyword(s):

Male Sterility ◽

House Mouse ◽

Genetic Background ◽

Genetic Architecture ◽

Hybrid Male ◽

Hybrid Male Sterility ◽

X Chromosomes ◽

Age Related ◽

Age Dependent ◽

In The Wild

AbstractHybrid male sterility (HMS) contributes to reproductive isolation commonly observed among house mouse (Mus musculus) subspecies, both in the wild and in laboratory crosses. Incompatibilities involving specific Prdm9 alleles and certain Chromosome (Chr) X genotypes are known determinants of fertility and HMS, and previous work in the field has demonstrated that genetic background modifies these two major loci. We constructed hybrids that have identical genotypes at Prdm9 and identical X chromosomes, but differ widely across the rest of the genome. In each case, we crossed female PWK/PhJ mice representative of the M. m. musculus subspecies to males from a classical inbred strain representative of M. m. domesticus: 129S1/SvImJ, A/J, C57BL/6J, or DBA/2J. We detected three distinct trajectories of fertility among the hybrids using breeding experiments. The PWK129S1 males were always infertile. PWKDBA2 males were fertile, despite their genotypes at the major HMS loci. We also observed age-dependent changes in fertility parameters across multiple genetic backgrounds. The PWKB6 and PWKAJ males were always infertile before 15 weeks and after 35 weeks, yet some PWKB6 and PWKAJ males were fertile between fifteen and 35 weeks. This observation could resolve previous contradictory reports about the fertility of PWKB6. Taken together, these results point to multiple segregating HMS modifier alleles, some of which have age-related modes of action. The ultimate identification of these alleles and their age-related mechanisms will advance understanding both of the genetic architecture of HMS and of how reproductive barriers are maintained between house mouse subspecies.

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Genetic Architecture of Hybrid Male Sterility in Drosophila: Analysis of Intraspecies Variation for Interspecies Isolation

PLoS ONE ◽

10.1371/journal.pone.0003076 ◽

2008 ◽

Vol 3 (8) ◽

pp. e3076 ◽

Cited By ~ 18

Author(s):

Laura K. Reed ◽

Brooke A. LaFlamme ◽

Therese A. Markow

Keyword(s):

Male Sterility ◽

Genetic Architecture ◽

Hybrid Male ◽

Hybrid Male Sterility ◽

Intraspecies Variation

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Age and genetic background determine hybrid male sterility in house mice

10.1101/382382 ◽

2018 ◽

Author(s):

Samuel J. Widmayer ◽

David L. Aylor

Keyword(s):

Reproductive Isolation ◽

Male Sterility ◽

Genetic Factors ◽

Inbred Strains ◽

House Mice ◽

Reproductive Barriers ◽

Hybrid Male ◽

Hybrid Male Sterility ◽

Unique Type ◽

Age Dependent

AbstractHybrid male sterility (HMS) is a unique type of reproductive isolation commonly observed between house mouse (Mus musculus) subspecies in the wild and in laboratory crosses. We identified hybrids that display three distinct trajectories of fertility despite having identical genotypes at the major HMS gene Prdm9 and the X Chromosome. In each case, we crossed female PWK/PhJ mice representative of the M.m.musculus subspecies to males from classical inbred strains representative of M.m.domesticus: 129S1/SvImJ, A/J, C57BL/6J, and DBA/2J. PWK129S1 males are always sterile, while PWKDBA2 males escape HMS. In addition, we observe age-dependent sterility in PWKB6 and PWKAJ males. These males are fertile between 15 and 35 weeks with moderate penetrance. These results point to multiple segregating HMS modifier alleles, some of which have an age-dependent mode of action. Age-dependent mechanisms could have broad implications for the maintenance of reproductive barriers in nature.Author SummaryTwo subspecies of house mice show partial reproductive barriers in nature, and may be in the process of speciation. We used mice derived from each subspecies to replicate hybrid male sterility (HMS) in laboratory mice. Two major genetic factors are well established as playing a role in mouse HMS, but the number of additional factors and their mechanisms are unknown. We characterized reproductive trait variation in a set of hybrid male mice that were specifically designed to eliminate the effects of known genetic factors. We discovered that age played an important role in fertility of some hybrids. These hybrid males showed a delayed onset of fertility, then became fertile for only a few weeks. Across all hybrids males in our study, we observed three distinct trajectories of fertility: complete fertility, complete sterility, and age-dependent fertility. These results point to two or more critical HMS variants with large enough effects to completely restore fertility. This study advances our understanding of the genetic architecture and biological mechanisms of reproductive isolation in mice.

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Genetic Architecture of Autosome-Mediated Hybrid Male Sterility in Drosophila

Genetics ◽

10.1093/genetics/142.4.1169 ◽

1996 ◽

Vol 142 (4) ◽

pp. 1169-1180

Author(s):

Ignacio Marín

Keyword(s):

Male Sterility ◽

Genetic Architecture ◽

Relative Size ◽

Drosophila Species ◽

Hybrid Male ◽

Hybrid Male Sterility ◽

Reciprocal Crosses ◽

Drosophila Buzzatii ◽

Number Of Factors ◽

Two Factors

Abstract Several estimators have been developed for assesing the number of sterility factors in a chromosome based on the sizes of fertile and sterile introgressed fragments. Assuming that two factors are required for producing sterility, simulations show that one of these, twice the inverse of the relative size of the largest fertile fragment, provides good average approximations when as few as five fertile fragments are analyzed. The estimators have been used for deducing the number of factors from previous data on several pairs of species. A particular result contrasts with the authors' interpretations: instead of the high number of sterility factors suggested, only a few per autosome are estimated in both reciprocal crosses involving Drosophila buzzatii and D. koepferae. It has been possible to map these factors, between three and six per chromosome, in the autosomes 3 and 4 of these species. Out of 203 introgressions of different fragments or combinations of fragments, the outcome of at least 192 is explained by the mapped zones. These results suggest that autosome-mediated sterility in the male hybrids of these species is mediated by a few epistatic factors, similarly to X-mediated sterility in the hybrids of other Drosophila species.

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Faculty Opinions recommendation of Hybrid male sterility in rice controlled by interaction between divergent alleles of two adjacent genes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717963248.793465268 ◽

2012 ◽

Author(s):

John Willis

Keyword(s):

Male Sterility ◽

Hybrid Male ◽

Hybrid Male Sterility

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Hidden Effects of X Chromosome Introgressions on Spermatogenesis in Drosophila simulans × D. mauritiana Hybrids Unveiled by Interactions Among Minor Genetic Factors

Genetics ◽

10.1093/genetics/150.2.745 ◽

1998 ◽

Vol 150 (2) ◽

pp. 745-754 ◽

Cited By ~ 3

Author(s):

Xulio R Maside ◽

José P Barral ◽

Horacio F Naveira

Keyword(s):

Male Sterility ◽

X Chromosome ◽

Seminal Vesicles ◽

Genetic Dissection ◽

Research Strategies ◽

Hybrid Male ◽

Hybrid Male Sterility ◽

Epistatic Interactions ◽

Drosophila Mauritiana ◽

Chromosome Segments

Abstract One of the most frequent outcomes of interspecific hybridizations in Drosophila is hybrid male sterility. Genetic dissection of this reproductive barrier has revealed that the number of responsible factors is very high and that these factors are frequently engaged in complex epistatic interactions. Traditionally, research strategies have been based on contrasting introgressions of chromosome segments that produce male sterility with those that allow fertility. Few studies have investigated the phenotypes associated with the boundary between fertility and sterility. In this study, we cointrogressed three different X chromosome segments from Drosophila mauritiana into D. simulans. Hybrid males with these three segments are usually fertile, by conventional fertility assays. However, their spermatogenesis shows a significant slowdown, most manifest at lower temperatures. Each of the three introgressed segments retards the arrival of sperm to the seminal vesicles. Other small disturbances in spermatogenesis are evident, which altogether lead to an overall reduction in the amount of motile sperm in their seminal vesicles. These results suggest that a delay in the timing of spermatogenesis, which might be brought about by the cumulative action of many different factors of minor segment, may be the primary cause of hybrid male sterility.

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Genetic Complexity Underlying Hybrid Male Sterility in Drosophila

Genetics ◽

10.1093/genetics/166.2.789 ◽

2004 ◽

Vol 166 (2) ◽

pp. 789-796 ◽

Cited By ~ 1

Author(s):

Kyoichi Sawamura ◽

John Roote ◽

Chung-I Wu ◽

Masa-Toshi Yamamoto

Keyword(s):

Male Sterility ◽

Related Species ◽

Synergistic Effects ◽

Female Sterility ◽

Hybrid Male ◽

Hybrid Female ◽

Hybrid Male Sterility ◽

Closely Related Species ◽

Genetic Complexity ◽

Recessive Genes

Abstract Recent genetic analyses of closely related species of Drosophila have indicated that hybrid male sterility is the consequence of highly complex synergistic effects among multiple genes, both conspecific and heterospecific. On the contrary, much evidence suggests the presence of major genes causing hybrid female sterility and inviability in the less-related species, D. melanogaster and D. simulans. Does this contrast reflect the genetic distance between species? Or, generally, is the genetic basis of hybrid male sterility more complex than that of hybrid female sterility and inviability? To clarify this point, the D. simulans introgression of the cytological region 34D-36A to the D. melanogaster genome, which causes recessive male sterility, was dissected by recombination, deficiency, and complementation mapping. The 450-kb region between two genes, Suppressor of Hairless and snail, exhibited a strong effect on the sterility. Males are (semi-)sterile if this region of the introgression is made homozygous or hemizygous. But no genes in the region singly cause the sterility; this region has at least two genes, which in combination result in male sterility. Further, the males are less fertile when heterozygous with a larger introgression, which suggests that dominant modifiers enhance the effects of recessive genes of male sterility. Such an epistatic view, even in the less-related species, suggests that the genetic complexity is special to hybrid male sterility.

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Specific Interactions Between Autosome and X Chromosomes Cause Hybrid Male Sterility in Caenorhabditis Species

Genetics ◽

10.1534/genetics.119.302202 ◽

2019 ◽

Vol 212 (3) ◽

pp. 801-813 ◽

Cited By ~ 4

Author(s):

Yu Bi ◽

Xiaoliang Ren ◽

Runsheng Li ◽

Qiutao Ding ◽

Dongying Xie ◽

...

Keyword(s):

Male Sterility ◽

Male Fertility ◽

Genetic Mechanism ◽

Hybrid Male ◽

Female Progeny ◽

Hybrid Male Sterility ◽

Male And Female ◽

F1 Progeny ◽

Asymmetric Hybrid ◽

Parent Of Origin

Hybrid male progeny from interspecies crosses are more prone to sterility or inviability than hybrid female progeny, and the male sterility and inviability often demonstrate parent-of-origin asymmetry. However, the underlying genetic mechanism of asymmetric sterility or inviability remains elusive. We previously established a genome-wide hybrid incompatibility (HI) landscape between Caenorhabditis briggsae and C. nigoni by phenotyping a large collection of C. nigoni strains each carrying a C. briggsae introgression. In this study, we systematically dissect the genetic mechanism of asymmetric sterility and inviability in both hybrid male and female progeny between the two species. Specifically, we performed reciprocal crosses between C. briggsae and different C. nigoni strains that each carry a GFP-labeled C. briggsae genomic fragment referred to as introgression, and scored the HI phenotypes in the F1 progeny. The aggregated introgressions cover 94.6% of the C. briggsae genome, including 100% of the X chromosome. Surprisingly, we observed that two C. briggsaeX fragments that produce C. nigoni male sterility as an introgression rescued hybrid F1 sterility in males fathered by C. briggsae. Subsequent backcrossing analyses indicated that a specific interaction between the X-linked interaction and one autosome introgression is required to rescue the hybrid male sterility. In addition, we identified another two C. briggsae genomic intervals on chromosomes II and IV that can rescue the inviability, but not the sterility, of hybrid F1 males fathered by C. nigoni, suggesting the involvement of differential epistatic interactions in the asymmetric hybrid male fertility and inviability. Importantly, backcrossing of the rescued sterile males with C. nigoni led to the isolation of a 1.1-Mb genomic interval that specifically interacts with an X-linked introgression, which is essential for hybrid male fertility. We further identified three C. briggsae genomic intervals on chromosome I, II, and III that produced inviability in all F1 progeny, dependent on or independent of the parent-of-origin. Taken together, we identified multiple independent interacting loci that are responsible for asymmetric hybrid male and female sterility, and inviability, which lays a foundation for their molecular characterization.

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