Reciprocal F1 Hybrids Research Articles

Genetic background affects the strength of crossover interference in house mice.

Meiotic recombination is required for faithful chromosome segregation in most sexually reproducing organisms and shapes the distribution of genetic variation in populations. Both the overall rate and the spatial distribution of crossovers vary within and between species. Adjacent crossovers on the same chromosome tend to be spaced more evenly than expected at random, a phenomenon known as crossover interference. Although interference has been observed in many taxa, the factors that influence the strength of interference are not well understood. We used house mice (Mus musculus), a well-established model system for understanding recombination, to study the effects of genetics and age on recombination rate and interference in the male germline. We analyzed crossover positions in 503 progeny from reciprocal F1 hybrids between inbred strains representing the three major subspecies of house mice. Consistent with previous studies, autosomal alleles from M. m. musculus tend to increase recombination rate, while inheriting a M. m. musculus X chromosome decreases recombination rate. Old males transmit an average of 0.6 more crossovers per meiosis (5.0%) than young males, though the effect varies across genetic backgrounds. We show that the strength of crossover interference depends on genotype, providing a rare demonstration that interference evolves over short timescales. Differences between reciprocal F1s suggest that X-linked factors modulate the strength of interference. Our findings motivate additional comparisons of interference among recently diverged species and further examination of the role of paternal age in determining the number and positioning of crossovers.

The role of mitochondria in sex- and age-specific gene expression in a species without sex chromosomes

Mitochondria perform an array of functions, many of which involve interactions with gene products encoded by the nucleus. These mitochondrial functions, particularly those involving energy production, can be expected to differ between sexes and across ages. Here, we measured mitochondrial effects on sex- and age-specific gene expression in parental and reciprocal F1 hybrids between allopatric populations of Tigriopus californicus with over 20% mitochondrial DNA divergence. Because the species lacks sex chromosomes, sex-biased mitochondrial effects are not confounded by the effects of sex chromosomes. Results revealed pervasive sex differences in mitochondrial effects, including effects on energetics and aging involving nuclear interactions throughout the genome. Using single-individual RNA sequencing, sex differences were found to explain more than 80% of the variance in gene expression. Males had higher expression of mitochondrial genes and mitochondrially targeted proteins (MTPs) involved in oxidative phosphorylation (OXPHOS), while females had elevated expression of non-OXPHOS MTPs, indicating strongly sex-dimorphic energy metabolism at the whole organism level. Comparison of reciprocal F1 hybrids allowed insights into the nature of mito-nuclear interactions, showing both mitochondrial effects on nuclear expression, and nuclear effects on mitochondrial expression. While based on a small set of crosses, sex-specific increases in mitochondrial expression with age were associated with longer life. Network analyses identified nuclear components of strong mito-nuclear interactions and found them to be sexually dimorphic. These results highlight the profound impact of mitochondria and mito-nuclear interactions on sex- and age-specific gene expression.

Divergence in Reproductive Behaviors Is Associated with the Evolutionary Loss of Parental Care.

AbstractThe mechanisms underlying the divergence of reproductive strategies between closely related species are still poorly understood. Additionally, it is unclear which selective factors drive the evolution of reproductive behavioral variation and how these traits coevolve, particularly during early divergence. To address these questions, we quantified behavioral differences in a recently diverged pair of Nova Scotian three-spined stickleback (Gasterosteus aculeatus) populations, which vary in parental care, with one population displaying paternal care and the other lacking this. We compared both populations, and a full reciprocal F1 hybrid cross, across four major reproductive stages: territoriality, nesting, courtship, and parenting. We identified significant divergence in a suite of heritable behaviors. Importantly, F1 hybrids exhibited a mix of behavioral patterns, some of which suggest sex linkage. This system offers fresh insights into the coevolutionary dynamics of reproductive behaviors during early divergence and offers support for the hypothesis that coevolutionary feedback between sexual selection and parental care can drive rapid evolution of reproductive strategies.

Genetic Analyses of Flower Main Traits from Two Pitayas and Their Progenies: A Cactus Plant.

Elucidation of the genetic foundation governing crucial traits in pitaya flowers is imperative for enhancing both the ornamental and economic values. In this study, the dynamic variation in flower genetics, segregation variation patterns, and a mixed inheritance model of the major and multigene flower traits of 'Dahong' and 'Honghuaqinglong' pitayas and their progenies were explored. The results showed that the main traits of flowers exhibited varying degrees of variation among the reciprocal F1 hybrids, with the data exhibiting the characteristics of quantitative traits. The betalain content, petal number, and stigma number exhibited values below the median values of the parents, suggesting a genetic inclination towards lower values. Perianth width, calyx tube width, petal number, and stigma number had the same genetic effects and significant correlation. Stigma-related traits had a clear maternal inheritance tendency. The heritability of flower length, stigma relative to anther distance, and petal betalain content was governed by two pairs of additive-dominant major genes. Perianth width, calyx tube width, petal number, and stigma number all conformed to the model of two pairs of equal-additive-dominant major genes. This study provides valuable information for parental selection, cross-breeding, and the enhancement of pitaya varieties to meet market preferences and environmental conditions.

Comparison of pure caucasian, carniolan and native anatolian ecotype honey bee (Apis mellifera L.) colonies in the eastern anatolia region with reciprocal F1 hybrids

The aim of this study was to compare specific physiological and behavioral characteristics of A. m. caucasica, A. m. carnica, and native honeybees, as well as reciprocal crosses, within the ecological conditions of East Anatolia (Van province), Turkey. The findings revealed that native honeybees exhibited the highest average sealed brood area and the highest average number of frames with bees. In contrast, the highest average honey yield was observed in the crossbreeding of Carniolan bees with native bees. Significant differences were identified among the groups concerning brood area, the number of bee frames, aggression tendency, and honey yield. The study concluded that Carniolan and Caucasian bees exhibited suboptimal performance outside their native habitats. Nevertheless, Carniolan bees were identified as a viable option for mitigating aggression tendencies and enhancing honey yield in native bee populations.

Kinetic Characterization and Partial Purification of Peroxidase in Eucalyptus F1 Hybrids

A differential pattern of peroxidase (E.C. 1.1.11.7) has been observed in reciprocal F1 hybrids of Eucalyptus (FRI-4 and FRI-5) produced using parental combination of E. tereticornis and E. camaldulensis. The hybrids were characterized for the qualitative, kinetic parameters (total and specific activity, units, Km and Vmax) and partial purification of peroxidase. The qualitative study showed the presence of high molecular weight peroxidase isoforms i.e. 260 KD, 250 KD and 110KD bands. A strong maternal inheritance was observed for 260 KD loci in FRI-5. Kinetic characterization of peroxidase revealed that F1 genotypes had efficient peroxidase system over their parental combination resulting in 8 -10 times more heterotic vigour. The FRI-5 genotypes were found to be having efficient peroxidase system with lowest Km values (0.12mM-0.17mM) and higher Vmax values ranging from 0.07-0.14mM min-1mg prot-1. The study revealed the role of maternal inheritance and was found that better genotypes are produced when superior parents are used as seed parent. The results suggest the efficient use of peroxidase marker for the identification of the better genotypes in forest tree species.

Disproportionate role of nuclear-encoded proteins in organismal and mitochondrial thermal performance in a copepod.

Determining the mechanisms by which organisms evolve thermal tolerance is crucial to predicting how populations may respond to changes in local temperature regimes. Although evidence of relationships between mitochondrial background and thermal adaptation have been found, the presence of both nuclear-encoded and mitochondrial DNA (mtDNA)-encoded proteins warrants experiments aimed at parsing out the relative role of each genome in thermal adaptation. We investigated the relative role of mtDNA-encoded products in thermal tolerance between two divergent populations of Tigriopus californicus using first-generation (F1) hybrids that vary in maternally inherited mtDNA but are heterozygous for population-specific alleles across nuclear loci. We tested two measures of thermal tolerance, (1) survivorship to acute thermal stress and (2) thermal stability of mitochondrial performance in Complex I-fueled ATP synthesis, both across a range of increasing temperatures. We found that the southern population (San Diego, CA, USA) outperformed the northern population (Strawberry Hill, OR, USA) in survivorship, and that both reciprocal F1 hybrid crosses had intermediate survival. Mitochondria from the San Diego population displayed greater stability in ATP synthesis with increasing temperatures compared with those from Strawberry Hill. Interestingly, hybrids from both cross directions had synthesis profiles that were very similar to that of Strawberry Hill. Taken together, these results suggest that the relative role of the mtDNA in these phenotypes is negligible compared with that of elements encoded by nuclear DNA in this system.

Transposable elements and gene expression variation in the intraspecific hybrids of Capsella rubella

AbstractTransposable elements (TEs) are prevalent components of diverse genomes, and play an important role on the genomic stability and expression regulation of their adjacent genes. It is interesting to know the variation of TE expression and the effects of the presence/absence of TEs on gene expression after hybridization. Here we assessed the expression variation of TEs and the impacts of TEs on expression of nearby genes after hybridization based on comparisons of three pairs of reciprocal F1 hybrids and four parents in Capsella rubella. Of the 480 TE families expressed in all the four parents and six F1 hybrids, 7–23 (1.5%–4.2%) TE families were significantly differentially expressed between in silico and real F1 hybrids, indicating the expression levels of these TE families were affected during hybridization. In particular, there was a Copia TE superfamily and a non‐long terminal repeat (non‐LTR) TE differentially expressed between the reciprocal F1 hybrids of 879 and 86IT1, indicating maternal effects may have impacts on expression of TEs in these F1 hybrids. Besides the impacts on the expression of TE families of the hybridization, genes adjacent to polymorphic TEs tended to show a higher proportion (24.83%) of allele‐specific expression (ASE) in F1 hybrids. Overall, our results highlight the impacts of hybridization on the expression level variation of TEs, and the effects of TEs on ASE after hybridization.

Наследование признака высокого содержания олеиновой кислоты в масле семян F2 и поколения BC1 рапса озимого (Brassica napus L.)

The aim of the work was to study the patterns of inheritance of the trait of high oleic content in the F2 and generation BC1 of winter rapeseed in order to obtain new knowledge about the genetic mechanisms of the high oleic acid contents in seed oil and scientifically based approaches to the development of the breeding germplasm with a high content of oleic acid. The studies were carried out in 2021– 2022 in the field. The material was reciprocal F1 hybrids from crossings of the high-oleic line VN-1848 (79.3%) and two lines from the cultivars Sarmat and Selegor of VNIIMK breeding with the traditional content of oleic acid in seed oil – 62.1 and 60.5%, respectively. Hybrids F1 were used to produce BC1 seeds. F2 and BC1 generations were obtained in 2022. In F2 hybrids, splitting into two phenotypic classes was observed in a ratio of 15 : 1. The first one included lines with oleic acid content in seed oil less than 79%, the second one – lines with high rates of this trait at the level or higher than the parental high-oleic component (18 : 1 > 79%). This proposes the control of a trait by two pairs of non-allelic genes with an additive effect. As a result of backcrosses using the high-oleic lines VN-1848 as the maternal component, 55 genotypes with a low content of oleic acid (18 : 1 < 79%) and 11 genotypes with high levels of this trait (18 : 1 > 79%) were obtained. This corresponded to a splitting ratio of 3 : 1. All χ2 values turned out to be less than 3.8, p > 0.05.The results of the studies confirm our assumption that the oleic acid content in seed oil is controlled by two pairs of non-allelic genes; the manifestation of this trait in plants is observed only when all alleles are in a homozygous recessive state.

Genome Shock in a Synthetic Allotetraploid Wheat Invokes Subgenome-Partitioned Gene Regulation, Meiotic Instability and Karyotype Variation.

It becomes increasingly evident that interspecific hybridization at homoploid level or coupled with whole genome duplication (i.e., allopolyploidization) has played a major role in biological evolution. Yet, the direct impact of hybridization and allopolyploidization on genome structure and function, phenotype, and fitness remains to be fully understood. Synthetic hybrids and allopolyploids are trackable experimental systems to address this issue. Here, we resynthesized a pair of reciprocal F1 hybrids and corresponding reciprocal allotetraploids using the two diploid progenitor species, Triticum urartu (AA) and Aegilops tauschii (DD), of bread wheat (Triticum aestivum L., BBAADD). By comparing phenotypes related to growth, development and fitness, andanalyzing genome expression in both hybrids and allotetraploids in relation to parents, we find the types and trends of karyotype variation in the immediately formed allotetraploids, are correlated with both meiosis instability and chromosome- and subgenome-biased expression. We document clear advantages of allotetraploids over diploid F1 hybrids in several morphological traits including fitness, which mirror the tissue- and developmental stage-dependent subgenome-partitioning of the allotetraploids. The allotetraploids are meiotically unstable primarily due to homoeologous pairing that varies dramatically among the chromosomes. Nonetheless, the manifestation of organismal karyotype variation and occurrence of meiotic irregularity are not concordant, suggesting a role of functional constraints probably imposed by subgenome- and chromosome-biased gene expression. Our results provide new insights into the direct impacts and consequences of hybridization and allopolyploidization, which are relevant to evolution and likely informative to crop improvement by synthetic polyploid approaches.

Backcrossing as a species restoration technique.

An investigation was conducted on the phenotypic results of mouse hybridization and seven generations of backcrossing, observing reciprocal F1 hybrids and backcrosses of Mus spretus and a laboratory strain of Mus domesticus C57BL/6J. F1 hybrids, backcrosses, and pure control specimens were measured for 6 body characteristics, 4 pelage coloration characteristics, 14 behaviors, and reproduction as reflected in litter size. Backcrossing was pursued for seven generations to FBC7 (i.e., "Backcross 7" or seven generations from commencement of backcrossing from an F1 hybrid female) where species restoration is mathematically calculated to be at 99.7%. Except for a minority of FBC7 M. spretus specimens failing to conform completely to one pelage characteristic, FBC7 specimens were indistinguishable from controls both subjectively and in all areas of measurement. The M. spretus backcross line was followed generation by generation and was largely conforming to controls by FBC4 at latest. The same effect was observed in the reciprocal M. domesticus backcross line. Fertility was negatively affected in F1 hybrids but restored or improved in backcross generations. Discussion is offered on hybridization and backcrossing as it occurs in nature and how it has been used or could be used as an additional ex situ tool in wildlife conservation efforts. It is concluded that conservation-oriented backcrossing is a practical species/subspecies restoration technique and has the potential to make genetic rescue feasible with minimal gene flow at the binomial level. Backcrossing is most applicable in closely monitored ex situ settings (1) where only one sex remains of a given taxon; and (2) where inbreeding depression seriously threatens a remnant taxon's ability to recover, and the only gene flow option is from another distinct species.

Comparison of the physicochemical properties of starches from maize reciprocal F1 hybrids and their parental lines

Heterosis on maize yield and quality is highly variable and depends on parental selection. This study investigated and compared the starch structure and physicochemical properties among four sweet-waxy maize lines, four waxy maize lines, and their eight reciprocal F1 hybrids. Compared with the sweet-waxy maize, waxy maize and F1 hybrids had lower extent of branching of amylopectin and relative crystallinity, and larger starch granule size. Waxy maize starch had higher breakdown viscosity and retrogradation percentage, and lower setback viscosity and gelatinization enthalpy than the sweet-waxy maize starch. Meanwhile, the peak and setback viscosities, and retrogradation enthalpy of most F1 hybrid starches were higher than those of their female parent, while gelatinization enthalpy was the opposite. The F1 hybrid starches had higher onset temperature and retrogradation percentage and lower gelatinization enthalpy than their male parent in general. In conclusion, this study provides a framework for the production of new hybrids.

Experimental comparison of changes in relative survival and fitness-related traits of wild, farm, and hybrid Atlantic salmon Salmo salar in nature

Farming of Atlantic salmon Salmo salar has resulted in highly domesticated individuals, with notable genetic and phenotypic differences from their wild counterparts. Understanding how interbreeding with aquaculture escapees affects wild, often at-risk populations is increasingly essential to conservation efforts. Here, we used an experimental release of wild, farm, and reciprocal F1 hybrid fry at 3 sites in the Garnish River in Newfoundland, Canada, to evaluate family and cross-specific patterns of recapture/survival, size, sex ratio, and precocial male maturation over a 28 mo period. Trends in cross type recapture changed over the study period, with the highest recapture at 3 mo in parr with wild mothers and between 15 and 28 mo in aquaculture offspring. Size trends among crosses and sites remained consistent over the study duration, with pure farm and wild-mother hybrids being consistently larger than wild individuals and 1 site displaying elevated sizes in all crosses. Rates of parr maturation differed by sex and cross type, and family-based analysis indicated family representation and size also remained consistent through time. These results indicate there is a difference in vital rates such as survival and precocial maturation between farm and wild Atlantic salmon during the freshwater early life history period, and this difference can change significantly over time. As such, an improved understanding of genetic and ecological interactions which takes this ontogenetic variation into account is likely essential to fully understand how hybridization and introgression with farm escapees are affecting wild populations.

Comparative transcriptomic reveals the molecular mechanism of maize hybrid Zhengdan538 in response to water deficit.

Heterosis, known as one of the most successful strategies for increasing grain yield and abiotic/biotic stress tolerance, has been widely exploited in maize breeding. However, the underlying molecular processes are still to be elucidated. The maize hybrid "Zhengdan538" shows high tolerance to drought stress. The transcriptomes of the seedling leaves of its parents, "ZhengA88" and "ZhengT22" and their reciprocal F1 hybrid under well-watered and water deficit conditions, were analyzed by RNA sequencing (RNA-Seq). Transcriptome profiling of the reciprocal hybrid revealed 2994-4692 differentially expressed genes (DEGs) under well-watered and water-deficit conditions, which were identified by comparing with their parents. The reciprocal hybrid was more closely related to the parental line "ZhengT22" than to the parental line "ZhengA88" in terms of gene expression patterns under water-deficit condition. Furthermore, genes showed expression level dominance (ELD), especially the high-parental ELD (Class 3 and 5), accounted for the largest proportion of DEGs between the reciprocal F1 hybrid and their parental lines under water deficit. These ELD genes mainly participated in photosynthesis, energy biosynthesis, and metabolism processes. The results indicated that ELD genes played important roles in hybrid tolerance to water deficit. Moreover, a set of important drought-responsive transcription factors were found to be encoded by the identified ELD genes and are thought to function in improving drought tolerance in maize hybrid plants. Our results provide a better understanding of the molecular mechanism of drought tolerance in hybrid maize.

Study on the inheritance of oleic acid content in reciprocal F1 hybrids of winter rapeseed at V.S. Pustovoit All-Russian Research Institute of Oil Crops

The purpose of the research was to study the inheritance of the trait of oleic acid content in oil of winter rapeseed seeds in reciprocal F1 hybrids. We carried out the research in 2019-2020 under field and greenhouse conditions. We used two high oleic lines for hybridization: BH 1844 (82.2 %) and BH 1848 (83.0 %), and two high-yielding lines from the varieties Sarmat and Selegor with a standard level of oleic acid of 62.1 and 60.5 %, respectively. Analysis of the C18:1 content of F1 hybrids, under field conditions, showed that in the case of crossing high oleic lines BH 1844 and BH 1848 with high-yielding lines from the varieties Sarmat and Selegor, five of eight combinations had an intermediate type of inheritance (h/d from -0.10 to 0.28). In the remaining three cases there was incomplete dominance of the trait (h/d from 0.56 to 0.64). We carried out similar studies in the phytotron greenhouse complex. On average, the content of C18:1 in the greenhouse conditions was 5.5 % lower in the high oleic lines, 0.3 % lower in the variety Sarmat, and 0.9 % lower in the variety Selegor, as oleic acid is synthesized less intensively at low air temperature. All the combinations of the greenhouse conditions showed an intermediate type of inheritance (h/d from -0.43 to 0.48). With this type of inheritance, lines combining high yield with high content of oleic acid can be isolated in the future.

Genetic architecture of protein expression and its regulation in the mouse brain

BackgroundNatural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6 J (B6) and DBA/2 J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology.ResultsBy comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and characterized the genetic basis of protein expression. We further applied a proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE), identifying 33 variant peptides with cis-effects and 17 variant peptides showing trans-effects. Comparison of regulation at transcript and protein levels show a significant divergence.ConclusionsThe results provide a comprehensive analysis of genetic architecture of protein expression and the contribution of cis- and trans-acting regulatory differences to protein expression.

Mitonuclear interactions alter sex-specific longevity in a species without sex chromosomes.

Impaired mitochondrial function can lead to senescence and the ageing phenotype. Theory predicts degenerative ageing phenotypes and mitochondrial pathologies may occur more frequently in males due to the matrilineal inheritance pattern of mitochondrial DNA observed in most eukaryotes. Here, we estimated the sex-specific longevity for parental and reciprocal F1 hybrid crosses for inbred lines derived from two allopatric Tigriopus californicus populations with over 20% mitochondrial DNA divergence. T. californicus lacks sex chromosomes allowing for more direct testing of mitochondrial function in sex-specific ageing. To better understand the ageing mechanism, we estimated two age-related phenotypes (mtDNA content and 8-hydroxy-20-deoxyguanosine (8-OH-dG) DNA damage) at two time points in the lifespan. Sex differences in lifespan depended on the mitochondrial and nuclear backgrounds, including differences between reciprocal F1 crosses which have different mitochondrial haplotypes on a 50 : 50 nuclear background, with nuclear contributions coming from alternative parents. Young females showed the highest mtDNA content which decreased with age, while DNA damage in males increased with age and exceed that of females 56 days after hatching. The adult sex ratio was male-biased and was attributed to complex mitonuclear interactions. Results thus demonstrate that sex differences in ageing depend on mitonuclear interactions in the absence of sex chromosomes.

Наследование признаков продуктивности колоса гибридами F1 яровой тритикале в условиях Владимирской области

The main method of breeding spring hexaploid Triticale is intravariety hybridization. At the same time, the effectiveness of breeding work depends on the correct selection of parental forms for crosses. However, the parental forms show different combining ability according to selective characteristics. In this regard, selection is more effective if it is based on information about their inheritance obtained through genetic analysis. The purpose of the research is to study the nature of inheritance of the main characteristics of productivity of the main ear (number of spikelets per ear, number of grains per ear, weight of grain per ear, weight of 1000 grains) hybrids of spring triticale F1 in agroecological conditions of the Vladimir region. The material of the study was 20 reciprocal hybrid combinations of spring triticale in comparison with the parental forms. To create hybrids of the first generation, four varieties of domestic selection and one Belarusian with high indicators of economically valuable traits were involved in hybridization. A different degree of phenotypic dominance has been established, which determines the type of inheritance of quantitative signs of productivity of the main ear. Reciprocal F1 hybrids differed in the degree of dominance from depression (negative overdominance) to heterosis (positive overdominance). The heterosis effect depended on which parental form was taken for the maternal, and which for the paternal. Hybrid F1 combinations with a high degree of overdominance of the main characteristics of the productivity of the main ear are identified: Lotas × Norman, Norman × Lotas, Norman × Grebeschok, Amigo × Grebeschok, Amigo × Norman.

Transcriptome-Wide Analysis of RNA m6A Methylation and Gene Expression Changes Among Two Arabidopsis Ecotypes and Their Reciprocal Hybrids.

The remodeling of transcriptome, epigenome, proteome, and metabolome in hybrids plays an important role in heterosis. N(6)-methyladenosine (m6A) methylation is the most abundant type of post-transcriptional modification for mRNAs, but the pattern of inheritance from parents to hybrids and potential impact on heterosis are largely unknown. We constructed transcriptome-wide mRNA m6A methylation maps of Arabidopsis thaliana Col-0 and Landsberg erecta (Ler) and their reciprocal F1 hybrids. Generally, the transcriptome-wide pattern of m6A methylation tends to be conserved between accessions. Approximately 74% of m6A methylation peaks are consistent between the parents and hybrids, indicating that a majority of the m6A methylation is maintained after hybridization. We found a significant association between differential expression and differential m6A modification, and between non-additive expression and non-additive methylation on the same gene. The overall RNA m6A level between Col-0 and Ler is clearly different but tended to disappear at the allelic sites in the hybrids. Interestingly, many enriched biological functions of genes with differential m6A modification between parents and hybrids are also conserved, including many heterosis-related genes involved in biosynthetic processes of starch. Collectively, our study revealed the overall pattern of inheritance of mRNA m6A modifications from parents to hybrids and a potential new layer of regulatory mechanisms related to heterosis formation.

Differential accumulation of tau pathology between reciprocal F1 hybrids of rTg4510 mice

Tau, a family of microtubule-associated proteins, forms abnormal intracellular inclusions, so-called tau pathology, in a range of neurodegenerative diseases collectively known as tauopathies. The rTg4510 mouse model is a well-characterized bitransgenic F1 hybrid mouse model of tauopathy, which was obtained by crossing a Camk2α-tTA mouse line (on a C57BL/6 J background) with a tetO-MAPT*P301L mouse line (on a FVB/NJ background). The aim of this study was to investigate the effects of the genetic background and sex on the accumulation of tau pathology in reciprocal F1 hybrids of rTg4510 mice, i.e., rTg4510 on the (C57BL/6 J × FVB/NJ)F1 background (rTg4510_CxF) and on the (FVB/NJ × C57BL/6 J)F1 background (rTg4510_FxC). As compared with rTg4510_CxF mice, the rTg4510_FxC mice showed marked levels of tau pathology in the forebrain. Biochemical analyses indicated that the accumulation of abnormal tau species was accelerated in rTg4510_FxC mice. There were strong effects of the genetic background on the differential accumulation of tau pathology in rTg4510 mice, while sex had no apparent effect. Interestingly, midline-1 (Mid1) was identified as a candidate gene associated with this difference and exhibited significant up/downregulation according to the genetic background. Mid1 silencing with siRNA induced pathological phosphorylation of tau in HEK293T cells that stably expressed human tau with the P301L mutation, suggesting the role of Mid1 in pathological alterations of tau. Elucidation of the underlying mechanisms will provide novel insights into the accumulation of tau pathology and is expected to be especially informative to researchers for the continued development of therapeutic interventions for tauopathies.