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Sperm Quality Parameters Are Increased and Asymmetric in House Mouse Hybrids

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Sperm Quality Parameters Are Increased and Asymmetric in House Mouse Hybrids bioRxiv preprint doi: https://doi.org/10.1101/666511; this version posted June 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Sperm quality parameters are increased and asymmetric in house mouse hybrids 2 3 Iva Martincová1,2,*, Ľudovít Ďureje1, Stuart J. E. Baird1, Jaroslav Piálek1 4 1 Research Facility Studenec, Institute of Vertebrate Biology, Czech Academy of Sciences, Brno, 5 Czech Republic 6 2 Department of Botany and Zoology, Faculty of Science, Masaryk University, Brno, Czech Republic 7 8 *Corresponding author: 9 Iva Martincová 10 Research Facility Studenec, 11 Institute of Vertebrate Biology, 12 Czech Academy of Sciences, 13 Květná 8, 603 65 Brno, 14 Czech Republic 15 [email protected] 16 17 ORCID iD: 18 Iva Martincová: 0000-0001-5066-0849 19 Stuart J. E. Baird: 0000-0002-7144-9919 20 Jaroslav Piálek: 0000-0002-0829-7481 bioRxiv preprint doi: https://doi.org/10.1101/666511; this version posted June 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 21 Abstract 22 Spermatogenesis is a tuned cascade of processes producing sperm; impairment of any phase of 23 this process can affect fitness of males. The level of impairment can be pronounced in hybrids 24 between genetically divergent populations. To explore the effect of hybridization on sperm quality 25 we produced F1 hybrids from 29 wild derived strains of two house mouse subspecies, M. m. 26 musculus and M. m. domesticus, which diverged 0.5 MY ago. The measured sperm quality traits 27 did not significantly differ between intrasubspecific crosses. Effects of intersubspecific 28 hybridization were dependent on sperm trait and cross direction. The proportion of sperm head 29 abnormalities was increased in F1 intersubspecific hybrids. The frequency of dissociated sperm 30 heads was increased in the M. m. musculus x M. m. domesticus (♀×♂) F1 but decreased in M. m. 31 domesticus x M. m. musculus (♀×♂) F1 hybrids, with the difference in medians being more than 32 180%. We deduce that the dissociated sperm heads trait is associated with the X chromosome and 33 modulated by interaction with the Y chromosome; nevertheless, the high proportion of 34 unexplained variance (55.46 %) suggests the presence of polymorphic autosomal interactions. The 35 reported differences in sperm quality between cross types may be highly relevant to male fitness 36 in zones of secondary contact between the two subspecies. The cross direction asymmetry in 37 frequency of dissociated sperm heads should favour the M. m. musculus Y chromosome. This is 38 consistent with the spread of the M. m. musculus Y chromosome in nature across the hybrid zone 39 between these two subspecies. 40 41 Keywords: Mus musculus musculus, Mus musculus domesticus, phenotype variation, sperm heads, 42 wild-derived strains bioRxiv preprint doi: https://doi.org/10.1101/666511; this version posted June 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 43 Acknowledgements 44 We thank Jakub Kreisinger for statistical advice, and Lidka Rousková, Helena Hejlová, Iva 45 Pospíšilová, and Jana Piálková for the welfare provided to the experimental mice. 46 This study was supported by the Czech Science Foundation (Projects 17-25320S and 19-12774S) 47 and the ROZE program of the Czech Academy of Sciences. The funding agencies played no role in 48 the design of the study, the collection, analysis, and interpretation of data and in writing the 49 manuscript. bioRxiv preprint doi: https://doi.org/10.1101/666511; this version posted June 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 50 Introduction 51 Lower fertility in males due to abnormal spermatozoa has been reported in many animals including 52 humans, but its pathogenic causes, including genetic factors, remain largely unknown (Chen et al. 53 2016). Data from knockout mice suggest that numerous genes can impair spermiogenesis (reviewed 54 in Chen et al. 2016). In nature, the incidence of genetically induced abnormalities can be affected 55 due to hybridization between diverged populations in zones of secondary contact (Alund et al. 56 2013). Decreased sperm quality will tend to reduce, and improved sperm quality increase, the 57 spread of causal genes. The amplitude of abnormal sperm morphology changes will be modulated 58 by geographic standing variation, affecting gene flow at local scales. Nevertheless, in some traits 59 hybridization may reveal species-specific effects, affecting gene flow at wider scales along contact 60 zones. 61 The house mouse hybrid zone (HMHZ) between Mus musculus musculus and M. m. domesticus 62 whose genomes diverged 0.5 MY ago is among the best studied animal hybrid zones (Baird & 63 Macholán 2012). The zone stretches across Europe from Norway to Bulgaria; more than 2500 km 64 long, itis only 10-20 km wide. The enigmatic behaviour of the sex chromosomes has been especially 65 challenging to our understanding of the extent and causality of introgressive hybridization 66 (Albrechtová et al. 2012). While introgression of the X chromosome is limited in comparison with 67 the autosomal loci Y introgression seems widespread along an 850 km of the contact in Central 68 Europe, and highly asymmetric: Ymusculus invades the domesticus background, the converse being 69 extremely rare (Macholán et al. 2007, 2008, Ďureje et al. 2012). 70 To explore the conditions of this Y chromosome spread in a wider context we earlier derived 31 71 recombinant lines from eight wild-derived strains representing four localities within the two mouse 72 subspecies (Martincová et al. 2019). These strains were first crossed within either subspecies and 73 subsequently reciprocally crossed to raise intersubspecific hybrids. The resulting F1 hybrid males bioRxiv preprint doi: https://doi.org/10.1101/666511; this version posted June 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 74 were scored for five phenotypic traits associated with male fitness. Hierarchical analysis of 75 reproductive traits in F1 hybrids with recombined intrasubspecific genomes revealed that body and 76 testis weights and sperm count differed on local scales (i.e. between localities and strains within 77 subspecies) but not at the intersubspecific level (Martincová et al. 2019). On the other hand, two 78 sperm quality traits (frequency of abnormal sperm heads (ASH) and frequency of dissociated sperm 79 heads from tail (DSH)) displayed Y-associated differentiation at the intersubspecific level. In both 80 cases the F1 hybrids with Ymusculus performed better than the F1 hybrids possessing Ydomesticus. 81 However, hierarchical model analysis suggested that the signal detected at the intersubspecific level 82 in ASH might be spurious, rather caused by interactions between one specific Ydomesticus haplotype 83 and the X or autosomes in recombinant lines. 84 In this paper we explore the replicability and generality of the sperm quality observations for 8 Y 85 haplotypes reported by (Martincová et al. 2019). Increasing sample size such that representative 86 genetic variation is captured within each of the subspecies and inter- and intrasubspecific F1 hybrid 87 comparisons we address two questions: (1) Are the proportions of deformed sperm in 88 intersubspecific hybrids different in comparison with intrasubspecific F1 hybrids? (2) Is the sperm 89 quality in intersubspecific F1 hybrids dependent on cross direction and, if so, are frequencies of DSH 90 and ASH decreased in the domesticus × musculus (♀ x ♂) male progeny when compared with the 91 musculus × domesticus (♀ x ♂) male progeny? Such a comparative study of the same set of sperm- 92 related traits across different experimental replicates tests the repeatability of subspecies-specific 93 phenotypic variation observations. 94 bioRxiv preprint doi: https://doi.org/10.1101/666511; this version posted June 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 95 Methods 96 Animals 97 The 29 wild-derived strains used to produce F1 hybrids are maintained in the breeding facility of the 98 Institute of Vertebrate Biology in Studenec (Piálek et al. 2008; licences for keeping animals and 99 experimental work 61974/2017-MZE-17214 and 62065/2017-MZE-17214, respectively). Fourteen 100 of them were derived at University of Montpellier by Annie Orth and François Bonhomme and 101 donated to Studenec in 2017 and 2018. PWD was derived in the Institute of Molecular Genetics 102 (Gregorová & Forejt 2000). Sixteen strains represent sampling of the wild standing variation of 103 domesticus genomes and 13 strains musculus genomes. Their distribution captures a wealth of 104 genetic variation present within a geographic area covering almost 8.5 M km2. Detailed information 105 on the origin of wild-derived strains and numbers of mated sires and dams used are listed in Table 106 1 and can also be retrieved at https://housemice.cz/. Numbers of sires used to generate intra- 107 and/or intersubspecific hybrids ranged between 1-18 (mean ± SD: 6.14 ± 4.69) and the numbers of 108 dams ranged between 1-15 (7.00 ± 4.49). In total, we scored 178 unique F1 males representing 34 109 domesticus × domesticus, 61 domesticus × musculus,42 musculus × domesticus and 42 musculus × 110 musculus crosses. Note, in all notifications of crosses, the female precedes the male (♀ × ♂). Each 111 male was derived from a unique pair of parents and their data are considered independent.
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