Biparental Inheritance Research Articles

Utilization of a SNP microarray to detect uniparental disomy: Implications and outcomes

PurposeTo examine the utility of single-nucleotide polymorphisms (SNP) microarray analysis to detect uniparental disomy (UPD) by utilizing trios and duos (for which only 1 parent is available). MethodsWe established Mendelian Inheritance Error (MIE) values associated with either UPD or biparental inheritance in a cohort of 124 patients. In duos, the percentage of proband heterozygous (AB) SNPs contributed from the parent submitted was also used to detect UPD. ResultsExamination of 25 trios revealed UPD with a MIE = 0.02 +/− 0.02 and a range of 0.01 to 0.23 for the contributing parent and a MIE = 8.76 +/− 1.68 with a range of 5.96 to 11.14 for the noncontributing parent. Detailed examination of 13 duos (involving 16 chromosomes) showed an AB% = 52.0% +/− 4.85% consistent with biparental origin of the chromosome of interest. In 6 duos (6 chromosomes), the AB% = 97.2% +/− 2.6% and a range of 92.9% to 99.4% were consistent with UPD. ConclusionOur results demonstrate utility of a SNP microarray to detect UPD. Distinct MIE ranges were observed that defined UPD or biparental inheritance. In duos, the AB% calculation effectively detected UPD. The diagnostic yield for UPD testing is significantly decreased when large regions of homozygosity are not detected by routine microarray analysis, which has implications for UPD test ordering practices.

Inheritance of Mitochondria in Pelargonium Section Ciconium (Sweet) Interspecific Crosses

We have studied the inheritance of mitochondria in Pelargonium section Ciconium using 36 interspecific crosses generated. We designed KASP markers targeting four mitochondrial loci, belonging to the mitomes of four main crossing parents, enabling tracking the transmission of each mitome in the crosses. These markers discriminate between an individual species versus the other section Ciconium species. We found that maternal inheritance of mitochondria is most frequent, with occasional occurrences of paternal inheritance, while biparental inheritance is rare. For a P. multibracteatum crossing series, we found ambiguous results. Our results confirm those of previous studies, namely, that paternal inheritance of mitochondria can occur in P. sect Ciconium but that the instance is rare and much less common than is the case for chloroplasts.

Phylogenomics and topological conflicts in the tribe Anthospermeae (Rubiaceae).

Genome skimming (shallow whole-genome sequencing) offers time- and cost-efficient production of large amounts of DNA data that can be used to address unsolved evolutionary questions. Here we address phylogenetic relationships and topological incongruence in the tribe Anthospermeae (Rubiaceae), using phylogenomic data from the mitochondrion, the nuclear ribosomal cistron, and the plastome. All three genomic compartments resolve relationships in the Anthospermeae; the tribe is monophyletic and consists of three major subclades. Carpacoce Sond. is sister to the remaining clade, which comprises an African subclade and a Pacific subclade. Most results, from all three genomic compartments, are statistically well supported; however, not fully consistent. Intergenomic topological incongruence is most notable in the Pacific subclade but present also in the African subclade. Hybridization and introgression followed by organelle capture may explain these conflicts but other processes, such as incomplete lineage sorting (ILS), can yield similar patterns and cannot be ruled out based on the results. Whereas the null hypothesis of congruence among all sequenced loci in the individual genomes could not be rejected for nuclear and mitochondrial data, it was rejected for plastid data. Phylogenetic analyses of three subsets of plastid loci identified using the hierarchical likelihood ratio test demonstrated statistically supported intragenomic topological incongruence. Given that plastid genes are thought to be fully linked, this result is surprising and may suggest modeling or sampling error. However, biological processes such as biparental inheritance and inter-plastome recombination have been reported and may be responsible for the observed intragenomic incongruence. Mitochondrial insertions into the plastome are rarely documented in angiosperms. Our results indicate that a mitochondrial insertion event in the plastid trnS GGA - rps4 IGS region occurred in the common ancestor of the Pacific clade of Anthospermeae. Exclusion/inclusion of this locus in phylogenetic analyses had a strong impact on topological results in the Pacific clade.

Paternal leakage of plastids rescues inter-lineage hybrids in Silene nutans.

Organelle genomes are usually maternally inherited in angiosperms. However, biparental inheritance has been observed, especially in hybrids resulting from crosses between divergent genetic lineages. When it concerns the plastid genome, this exceptional mode of inheritance might rescue inter-lineage hybrids suffering from plastid-nuclear incompatibilities. Genetically differentiated lineages of Silene nutans exhibit strong postzygotic isolation owing to plastid-nuclear incompatibilities, highlighted by inter-lineage hybrid chlorosis and mortality. Surviving hybrids can exhibit variegated leaves, which might indicate paternal leakage of the plastid genome. We tested whether the surviving hybrids inherited the paternal plastid genome and survived thanks to paternal leakage. We characterized the leaf phenotype (fully green, variegated or white) of 504 surviving inter-lineage hybrids obtained from a reciprocal cross experiment among populations of four genetic lineages (W1, W2, W3 and E1) of S. nutans from Western Europe and genotyped 560 leaf samples (both green and white leaves for variegated hybrids) using six lineage-specific plastid single nucleotide polymorphisms. A high proportion of the surviving hybrids (≤98 %) inherited the paternal plastid genome, indicating paternal leakage. The level of paternal leakage depended on cross type and cross direction. The E1 and W2 lineages as maternal lineages led to the highest hybrid mortality and to the highest paternal leakage from W1 and W3 lineages in the few surviving hybrids. This was consistent with E1 and W2 lineages, which contained the most divergent plastid genomes. When W3 was the mother, more hybrids survived, and no paternal leakage was detected. By providing a plastid genome potentially more compatible with the hybrid nuclear background, paternal leakage has the potential to rescue inter-lineage hybrids from plastid-nuclear incompatibilities. This phenomenon might slow down the speciation process, provided hybrid survival and reproduction can occur in the wild.

Plastid Inheritance Revisited: Emerging Role ofOrganelle DNA Degradation inAngiosperms.

Plastids are essential organelles in angiosperms and show non-Mendelian inheritance due to their evolution as endosymbionts. In approximately 80% of angiosperms, plastids are thought to be inherited from the maternal parent, whereas other species transmit plastids biparentally. Maternal inheritance can be generally explained by the stochastic segregation of maternal plastids after fertilization because the zygote is overwhelmed by the maternal cytoplasm. In contrast, biparental inheritance shows the transmission of organelles from both parents. In some species, maternal inheritance is not absolute and paternal leakage occurs at a very low frequency (∼10-5). A key process controlling the inheritance mode lies in the behavior of plastids during male gametophyte (pollen) development, with accumulating evidence indicating that the plastids themselves or their DNAs are eliminated during pollen maturation or at fertilization. Cytological observations in numerous angiosperm species have revealed several critical steps that mutually influence the degree of plastid transmission quantitatively among different species. This review revisits plastid inheritance from a mechanistic viewpoint. Particularly, we focus on a recent finding demonstrating that both low temperature and plastid DNA degradation mediated by the organelle exonuclease DEFECTIVE IN POLLEN ORGANELLE DNA DEGRADATION1 (DPD1) influence the degree of paternal leakage significantly in tobacco. Given these findings, we also highlight the emerging role of DPD1 in organelle DNA degradation.

Mitochondrial uniparental inheritance achieved after fertilization challenges the nuclear-cytoplasmic conflict hypothesis for anisogamy evolution.

In eukaryotes, a fundamental phenomenon underlying sexual selection is the evolution of gamete size dimorphism between the sexes (anisogamy) from an ancestral gametic system with gametes of the same size in both mating types (isogamy). The nuclear-cytoplasmic conflict hypothesis has been one of the major theoretical hypotheses for the evolution of anisogamy. It proposes that anisogamy evolved as an adaptation for preventing nuclear-cytoplasmic conflict by minimizing male gamete size to inherit organelles uniparentally. In ulvophycean green algae, biparental inheritance of organelles is observed in isogamous species, as the hypothesis assumes. So we tested the hypothesis by examining whether cytoplasmic inheritance is biparental in Monostroma angicava, a slightly anisogamous ulvophycean that produces large male gametes. We tracked the fates of mitochondria in intraspecific crosses with PCR-RFLP markers. We confirmed that mitochondria are maternally inherited. However, paternal mitochondria enter the zygote, where their DNA can be detected for over 14 days. This indicates that uniparental inheritance is enforced by eliminating paternal mitochondrial DNA in the zygote, rather than by decreasing male gamete size to the minimum. Thus, uniparental cytoplasmic inheritance is achieved by an entirely different mechanism, and is unlikely to drive the evolution of anisogamy in ulvophyceans.

O-180 What is the true potential of 1PN embryos? A report on utilisation and live birth rates following PGT-A and biparental testing

Abstract Study question What is the developmental potential of monopronuclear (1PN) embryos, and does allowing their use only after confirming biparental inheritance offer a clinical solution for them? Summary answer 1PN embryos demonstrate clear utilisation, euploidy, and live birth rates, that warrant their routine culture, and use following biparental inheritance testing, in the clinical setting. What is known already Embryos only displaying a single pronuclei (1PN) are widely regarded to be abnormal and not suitable for clinical use. It is therefore common practice to discard these embryos following fertilisation check. However, 1PN embryos have shown the ability for normal blastocyst development, albeit at a decreased rate, and the ability to produce live births. To bridge the gap between discarding an “abnormal” 1PN embryo, and the knowledge that it can result in a live birth, our clinic utilises PGT-A with biparental inheritance testing to assess the fitness of a 1PN embryo for transfer. Study design, size, duration A retrospective analysis was performed of 5010 1PN embryos derived from IVF (2612) or ICSI (2398) insemination at Genea clinics across Australia between January 2017 and November 2022. Blastocyst development, euploidy, parental inheritance, pregnancy, and live birth rates were analysed. Participants/materials, setting, methods Embryos were defined as being 1PN by the appearance of one pronuclei at fertilisation check 16-18 hours post insemination. Time lapse footage was reviewed on day 3 of culture to eliminate the late appearance of a second pronucleus. Suitable embryos underwent trophectoderm biopsy for PGT-A and biparental inheritance testing. Only euploid embryos with confirmed biparental inheritance were available to patients for frozen embryo transfer. Main results and the role of chance 1PN embryos derived from ICSI insemination were found to have a significantly lower blastocyst development potential of 17.4% compared to 33.7% for IVF embryos (p < 0.0001). The utilisation rate was also significantly lower at 8.1% for ICSI vs 21.2% for IVF (p < 0.0001). The IVF embryos showed a higher rate of euploidy following PGA-T testing, 50.9% for IVF vs 37.9% for ICSI (p < 0.0001). Uniparental inheritance, an indication the 1PN appearance was caused by parthenogenesis, was only observed in 6.7% of the total embryos tested, with IVF embryos having a considerably lower rate of 1.8% vs 20.5% for ICSI (p < 0.0001). There was no significant difference between the 2 groups for pregnancy rate or live births, following single embryo transfer, with 58.6% for IVF vs 62.9% for ICSI (p = 0.6) and 39.6% for IVF vs 45.7% for ICSI (p = 0.5) respectively. These levels were comparable to normally fertilised (2PN) euploid embryos across Genea clinics in the same time period. During the study period there have been 175 1PN embryos transferred that has resulted in 69 live births from embryos that otherwise would have been discarded. Limitations, reasons for caution The use of timelapse imaging from the time of insemination for ICSI embryos, as opposed to 16-18 hours post insemination for IVF embryos may play a role in the type of 1PN embryos that are being identified in each group. Wider implications of the findings This study demonstrates that not all 1PN embryos are abnormal and their routine use in the clinical IVF lab in conjunction with appropriate testing should be re-evaluated. Trial registration number not-applicable

O-078 Mosaic embryos – are they accurately detected by PGT-A?

Abstract Study question Following quantitative NGS for PGT-A, do current thresholds for mosaicism calling give a true reflection of the presumed mitotic origin of mosaic errors? Summary answer A large proportion of embryo mosaicism diagnosed following quantitative NGS-based PGT-A does not correlate with a true and expected mitotic origin, showing instead meiotic signatures. What is known already Mosaicism is a true biological phenomenon that can affect ongoing embryo development. However, the reproductive potential of mosaic embryos in assisted reproduction varies greatly across publications and is not fully understood. While the transfer of mosaic embryos could result in healthy live births, embryos containing meiotic errors almost never result in healthy live births. Since the clinical implications of meiotic and mitotic errors are very different, it is critical to accurately differentiate between the two. However, diagnosing mosaicism using current NGS-based PGT-A is not always accurate due to technical and biological limitations which may misclassify mosaic embryos. Study design, size, duration Follow-up analysis was carried out on 159 embryos previously categorised as mosaic by NGS-based PGT-A. To identify the origin of mosaic calls, SNP genotyping and karyomapping were performed on the same amplified DNA used for the clinical NGS analysis. Trophectoderm biopsy samples were obtained from embryos on days 5,6 or 7 of development from a single IVF centre between 2018-2022. For all PGT-A tested embryos, the reported mosaicism rate at the IVF centre was 12%. Participants/materials, setting, methods Samples were analysed using PGTai from CooperSurgical with a 30-80% CNV mosaicism range. Patients with mosaic embryos consented to karyomapping follow-up using sibling embryo reference DNA. The origin of mosaic events was defined by SNP inheritance patterns for the affected chromosome. Meiotic errors were defined by the presence of both haplotypes from one parent for trisomy, and the absence of a parental haplotype for monosomy. Mitotic errors were inferred following a result of biparental inheritance. Main results and the role of chance A total of 154 diploid embryos identified as mosaic by NGS-based PGT-A were re-analysed by SNP-genotyping. Of these, 30.5% (n = 47) displayed at least one error of meiotic origin following SNP genotyping. Among the 154 embryos, 189 mosaic chromosomal abnormalities were identified. After SNP-genotyping, 30.7% of chromosomal abnormalities (n = 58) showed evidence of meiotic signatures: 52 whole-chromosome (24 gains, 28 losses), and 6 segmental errors (5 gains and 1 loss). Of 73 segmental errors detected in total, only 8.2% of them (n = 6) were identified to be of meiotic origin. Following PGT-A, 7.8% of embryos (n = 12/154) displayed ≥3 chromosomal abnormalities in the mosaic range. Of these embryos, 58.3% (n = 7/12) displayed one or more meiotic aneuploidies. Overall, embryos showing multiple mosaic events were significantly more likely to have a least one error of meiotic origin than embryos containing one abnormality (McNemar’s test p-value= 1.171e-14). Among mosaic calls above 50% CNV, 56.7% (n = 55/97) showed evidence of meiotic origin. In contrast, but importantly, in the low-moderate mosaicism range <50% CNV, 3.3% of errors (3/92) also displayed meiotic signatures, including two whole chromosome errors (chr21 gain at 32% CNV and chr13 loss at 46% CNV), and one segmental error (dup(6)(pter-p12.1) at 33% CNV). Limitations, reasons for caution Since karyomapping relies on recombination events to identify meiotic trisomy, the true origin of intermediate copy-number changes cannot always be identified. Therefore, errors without recombination may be missed, potentially underestimating meiotic gains, especially segmentals. The absence of a parental haplotype cannot entirely rule-out a mitotic error from a biopsy sample. Wider implications of the findings Quantitative NGS methodologies are unable to accurately distinguish the origin of mosaic errors in PGT-A samples. Since the clinical impact of meiotic and mitotic errors differs greatly, this limitation could explain mosaic embryos’ reduced viability. Reliable identification of meiotic aneuploidies in presumed mosaic embryos is likely to improve clinical outcomes. Trial registration number not applicable

Evidence of Biparental Mitochondrial Inheritance from Self-Fertile Crosses between Closely Related Species of Ceratocystis.

Hybridization is recognized as a notable driver of evolution and adaptation, which closely related species may exploit in the form of incomplete reproductive barriers. Three closely related species of Ceratocystis (i.e., C. fimbriata, C. manginecans and C. eucalypticola) have previously been shown to hybridize. In such studies, naturally occurring self-sterile strains were mated with an unusual laboratory-generated sterile isolate type, which could have impacted conclusions regarding the prevalence of hybridization and inheritance of mitochondria. In the current study, we investigated whether interspecific crosses between fertile isolates of these three species are possible and, if so, how mitochondria are inherited by the progeny. For this purpose, a PCR-RFLP method and a mitochondrial DNA-specific PCR technique were custom-made. These were applied in a novel approach of typing complete ascospore drops collected from the fruiting bodies in each cross to distinguish between self-fertilizations and potential hybridization. These markers showed hybridization between C. fimbriata and C. eucalypticola and between C. fimbriata and C. manginecans, while no hybridization was detected in the crosses involving C. manginecans and C. eucalypticola. In both sets of hybrid progeny, we detected biparental inheritance of mitochondria. This study was the first to successfully produce hybrids from a cross involving self-fertile isolates of Ceratocystis and also provided the first direct evidence of biparental mitochondrial inheritance in the Ceratocystidaceae. This work lays the foundation for further research focused on investigating the role of hybridization in the speciation of Ceratocystis species and if mitochondrial conflict could have influenced the process.

Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons.

Baboons (genus Papio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high-coverage whole-genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and interspecies gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes.

Micro Germline-Restricted Chromosome in Blue Tits: Evidence for Meiotic Functions.

The germline-restricted chromosome (GRC) is likely present in all songbird species but differs widely in size and gene content. This extra chromosome has been described as either a microchromosome with only limited basic gene content or a macrochromosome with enriched gene functions related to female gonad and embryo development. Here, we assembled, annotated, and characterized the first micro-GRC in the blue tit (Cyanistes caeruleus) using high-fidelity long-read sequencing data. Although some genes on the blue tit GRC show signals of pseudogenization, others potentially have important functions, either currently or in the past. We highlight the GRC gene paralog BMP15, which is among the highest expressed GRC genes both in blue tits and in zebra finches (Taeniopygia guttata) and is known to play a role in oocyte and follicular maturation in other vertebrates. The GRC genes of the blue tit are further enriched for functions related to the synaptonemal complex. We found a similar functional enrichment when analyzing published data on GRC genes from two nightingale species (Luscinia spp.). We hypothesize that these genes play a role in maintaining standard maternal inheritance or in recombining maternal and paternal GRCs during potential episodes of biparental inheritance.

Chilling stress and loss of an exonuclease lead to biparental inheritance of plastids.

Chilling stress and loss of an exonuclease lead to biparental inheritance of plastids.

Hybridization drives mitochondrial DNA degeneration and metabolic shift in a species with biparental mitochondrial inheritance.

Mitochondrial DNA (mtDNA) is a cytoplasmic genome that is essential for respiratory metabolism. Although uniparental mtDNA inheritance is most common in animals and plants, distinct mtDNA haplotypes can coexist in a state of heteroplasmy, either because of paternal leakage or de novo mutations. mtDNA integrity and the resolution of heteroplasmy have important implications, notably for mitochondrial genetic disorders, speciation, and genome evolution in hybrids. However, the impact of genetic variation on the transition to homoplasmy from initially heteroplasmic backgrounds remains largely unknown. Here, we use Saccharomyces yeasts, fungi with constitutive biparental mtDNA inheritance, to investigate the resolution of mtDNA heteroplasmy in a variety of hybrid genotypes. We previously designed 11 crosses along a gradient of parental evolutionary divergence using undomesticated isolates of Saccharomyces paradoxus and Saccharomyces cerevisiae Each cross was independently replicated 48 to 96 times, and the resulting 864 hybrids were evolved under relaxed selection for mitochondrial function. Genome sequencing of 446 MA lines revealed extensive mtDNA recombination, but the recombination rate was not predicted by parental divergence level. We found a strong positive relationship between parental divergence and the rate of large-scale mtDNA deletions, which led to the loss of respiratory metabolism. We also uncovered associations between mtDNA recombination, mtDNA deletion, and genome instability that were genotype specific. Our results show that hybridization in yeast induces mtDNA degeneration through large-scale deletion and loss of function, with deep consequences for mtDNA evolution, metabolism, and the emergence of reproductive isolation.

Ongoing clinical pregnancy after the transfer of a one pronuclei (1PN) euploid embryo tested for bi-parental DNA inheritance with the Parent of Origin Test (PoOt)

Background and Aim: Embryos with only 1PN visible at the time of fertilisation check are usually discarded due to the lack of understanding about their true genetic content. In special circumstances, when there are no other 2PN embryos to utilise, these 1PN embryos can be used for embryo transfer (ET). However, the uncertainty around the outcomes of such procedures causes, distress and anxiety to patients.

Endangered Schizothoracin Fish in the Tarim River Basin Are Threatened by Introgressive Hybridization.

Simple SummaryInterspecific hybridization and introgression may threaten the survival of endangered species. Big-head Schizothoracin (Aspiorhynchus laticeps) and Tarim Schizothoracin (Schizothorax biddulphi) are two recognized types of fish of Schizothoracinae which belong to the family Cyprinidae. Big-head Schizothoracin and Tarim Schizothoracin are sympatrically distributed in the Tarim River basin in Xinjiang, China, and have been listed as first-class and second-class national key protected animals, respectively. Based on morphological characteristics, Schizothorax esocinus (another Schizothoracin that occurs in the Tarim River basin) is speculated to be hybrid offspring of Big-head Schizothoracin and Tarim Schizothoracin, but there is no direct genetic evidence for this point. In this study, the hybridization status of Schizothorax esocinus was confirmed by comparing genetic constitutions of mitochondrial DNA (mtDNA) and inter transcribed spacer (ITS2) encoded by the nuclear genome. Extensive hybridization and introgression between Big-head Schizothoracin and Tarim Schizothoracin was detected. Since both Big-head Schizothoracin and Tarim Schizothoracin are critically endangered fishes, risk management due to hybridization is recommended to be considered as a part of current conservation programs.Big-head Schizothoracin (Aspiorhynchus laticeps) and Tarim Schizothoracin (Schizothorax biddulphi) are locally sympatric in the Tarim River Basin. Although another Schizothoracin (Schizothorax esocinus) in Tarim River basin has been speculated to be hybrid offspring of Big-head Schizothoracin and Tarim Schizothoracin, there was no genetic evidence. Previous studies on the genetics and evolution of Schizothoracins in Xinjiang Province were mostly based on mitochondrial DNA (mtDNA), whose characteristics of maternal inheritance made it hard to answer the question of whether there was hybridization and introgression between Big-head Schizothoracin and Tarim Schizothoracin. In this study, cytochrome b (cytb) gene of mtDNA and internal transcribed spacer 2 (ITS2) that is encoded by the nuclear genome were genotyped within the entire samples at the same time. Our results confirmed that Schizothorax esocinus was the hybrid offspring of Big-head Schizothoracin and Tarim Schizothoracin. The heterozygous ITS2 genotypes and/or Aspiorhynchus laticeps-like mtDNA were also detected in a subset of samples that should have been identified as pure Schizothorax biddulphi based on morphology. The ITS2 is characterized by multi-copy, concert evolution, and biparental inheritance. Thus, by comparing with mtDNA data, broad-scale bidirectional hybridization and introgression between Big-head Schizothoracin and Tarim Schizothoracin were revealed. Although interspecific hybridization may play a positive role in ecology and evolution, interspecific hybrids could threaten their parental species by the swamping of genetics and demography. As both parents of hybridization are critically endangered fishes, in this case, it is urgently necessary to strengthen the scientific assessment of the risks of the hybrids and the control of the hybridization and introgression between Aspiorhynchus laticeps and Schizothorax biddulphi in the Tarim River Basin.

Genetic architecture facilitates then constrains adaptation in a host–parasite coevolutionary arms race

In coevolutionary arms races, interacting species impose selection on each other, generating reciprocal adaptations and counter adaptations. This process is typically enhanced by genetic recombination and heterozygosity, but these sources of evolutionary novelty may be secondarily lost when uniparental inheritance evolves to ensure the integrity of sex-linked adaptations. We demonstrate that host-specific egg mimicry in the African cuckoo finch Anomalospiza imberbis is maternally inherited, confirming the validity of an almost century-old hypothesis. We further show that maternal inheritance not only underpins the mimicry of different host species but also additional mimetic diversification that approximates the range of polymorphic egg “signatures” that have evolved within host species as an escalated defense against parasitism. Thus, maternal inheritance has enabled the evolution and maintenance of nested levels of mimetic specialization in a single parasitic species. However, maternal inheritance and the lack of sexual recombination likely disadvantage cuckoo finches by stifling further adaptation in the ongoing arms races with their individual hosts, which we show have retained biparental inheritance of egg phenotypes. The inability to generate novel genetic combinations likely prevents cuckoo finches from mimicking certain host phenotypes that are currently favored by selection (e.g., the olive-green colored eggs laid by some tawny-flanked prinia, Prinia subflava, females). This illustrates an important cost of coding coevolved adaptations on the nonrecombining sex chromosome, which may impede further coevolutionary change by effectively reversing the advantages of sexual reproduction in antagonistic coevolution proposed by the Red Queen hypothesis.

Genotype-Phenotype Correlations for Putative Haploinsufficient Genes in Deletions of 6q26-q27: Report of Eight Patients and Review of Literature.

Background Cytogenomic analyses have been used to detect pathogenic copy number variants. Patients with deletions at 6q26-q27 present variable clinical features. We reported clinical and cytogenomic findings of eight unrelated patients with a deletion of 6q26-q27. A systematic review of the literature found 28 patients with a deletion of 6q26-q27 from 2010 to 2020. Results For these 36 patients, the sex ratio showed equal occurrence between males and females; 29 patients (81%) had a terminal deletion and seven patients (19%) had a proximal or distal interstitial deletion. Of the 22 patients with parental studies, deletions of de novo, maternal, paternal, and bi-parental inheritance accounted for 64, 18, 14, and 4% of patients, respectively. The most common clinical findings were brain abnormalities (100%) in fetuses observed by ultrasonography followed by developmental delay and intellectual disability (81%), brain abnormalities (72%), facial dysmorphism (66%), hypotonia (63%), learning difficulty or language delay (50%), and seizures (47%) in pediatric and adult patients. Anti-epilepsy treatment showed the effect on controlling seizures in these patients. Cytogenomic mapping defined one proximal critical region at 6q26 containing the putative haploinsufficient gene PRKN and one distal critical region at 6q27 containing two haploinsufficient genes DLL1 and TBP . Deletions involving the PRKN gene could associate with early-onset Parkinson disease and autism spectrum disorder; deletions involving the DLL1 gene correlate with the 6q terminal deletion syndrome. Conclusion The genotype–phenotype correlations for putative haploinsufficient genes in deletions of 6q26-q27 provided evidence for precise diagnostic interpretation, genetic counseling, and clinical management of patients with a deletion of 6q26-q27.

Crataegus bretschneideri (Rosaceae), a separate species endemic to northeast China

Crataegus bretschneideri has been considered a variety of Crataegus pinnatifida, but has also been proposed as a separate species. We used ITS and three cpDNA sequence fragments (psbA‐trnH, trnG‐trnS, trnH‐trnK) to perform maximum parsimony, maximum likelihood, Bayesian inference and neighbor‐joining molecular phylogenetic analysis on 108 individuals of 19 hawthorn (Crataegus) species and 4 outgroups (Malus). The ITS, cpDNA and cpDNA‐ITS molecular phylogenetic trees constructed using 4 methods had similar consistency.In the cpDNA‐ITS tree, C. bretschneideri was resolved as an independent clade separated from Crataegus maximowiczii and C. pinnatifida. In the ITS (biparental inheritance) tree, C. bretschneideri and C. pinnatifida were resolved as closely related and only distantly related to C. maximowiczii. In contrast, the cpDNA (maternal inheritance) tree indicated that C. bretschneideri is closely related to C. maximowiczii but distantly related to C. pinnatifida. In total, 15 chloroplast haplotypes were revealed in the 108 Crataegus individuals, as determined by DNASP analysis. Of these, C. bretschneideri and C. maximowiczii share the same chloroplast haplotype, H1, while C. pinnatifida contains three haplotypes, H13–H15. Taken together with previous results, we confirm that C. bretschneideri is not a variety of C. pinnatifida, but a separate species that gradually developed from natural hybrid offspring in mixed forest areas with C. maximowiczii as the female parent and C. pinnatifida as the male parent.

Selection for biparental inheritance of mitochondria under hybridization and mitonuclear fitness interactions.

Uniparental inheritance (UPI) of mitochondria predominates over biparental inheritance (BPI) in most eukaryotes. However, examples of BPI of mitochondria, or paternal leakage, are becoming increasingly prevalent. Most reported cases of BPI occur in hybrids of distantly related sub-populations. It is thought that BPI in these cases is maladaptive; caused by a failure of female or zygotic autophagy machinery to recognize divergent male-mitochondrial DNA ‘tags’. Yet recent theory has put forward examples in which BPI can evolve under adaptive selection, and empirical studies across numerous metazoan taxa have demonstrated outbreeding depression in hybrids attributable to disruption of population-specific mitochondrial and nuclear genotypes (mitonuclear mismatch). Based on these developments, we hypothesize that BPI may be favoured by selection in hybridizing populations when fitness is shaped by mitonuclear interactions. We test this idea using a deterministic, simulation-based population genetic model and demonstrate that BPI is favoured over strict UPI under moderate levels of gene flow typical of hybridizing populations. Our model suggests that BPI may be stable, rather than a transient phenomenon, in hybridizing populations.

CLINICAL BENEFITS OF CULTURING INTRACYTOPLASMIC SPERM INJECTION-DERIVED NONPRONUCLEATED (0PN) AND MONOPRONUCLEATED (1PN) ZYGOTES, AND THE IMPORTANCE OF VERIFYING BIPARENTAL CHROMOSOME INHERITANCE IN 1PN-DERIVED BLASTOCYSTS

Evaluate the developmental competence and aneuploidy status of blastocysts derived from 0PN and 1PN zygotes following intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A). Elucidate biparental chromosome inheritance in female 1PN-derived blastocysts.