Phylogenomic discovery of deleterious mutations facilitates hybrid potato breeding.

Hybrid potato breeding will transform the crop from a clonally propagated tetraploid to a seed-reproducing diploid. Historical accumulation of deleterious mutations in potato genomes has hindered the development of elite inbred lines and hybrids. Utilizing a whole-genome phylogeny of 92 Solanaceae and its sister clade species, we employ an evolutionary strategy to identify deleterious mutations. The deep phylogeny reveals the genome-wide landscape of highly constrained sites, comprising ∼2.4% of the genome. Based on a diploid potato diversity panel, we infer 367,499 deleterious variants, of which 50% occur at non-coding and 15% at synonymous sites. Counterintuitively, diploid lines with relatively high homozygous deleterious burden can be better starting material for inbred-line development, despite showing less vigorous growth. Inclusion of inferred deleterious mutations increases genomic-prediction accuracy for yield by 24.7%. Our study generates insights into the genome-wide incidence and properties of deleterious mutations and their far-reaching consequences for breeding.

Genome evolution and diversity of wild and cultivated potatoes.

Potato (Solanum tuberosum L.) is the world's most important non-cereal food crop, and the vast majority of commercially grown cultivars are highly heterozygous tetraploids. Advances in diploid hybrid breeding based on true seeds have the potential to revolutionize future potato breeding and production1-4. So far, relatively few studies have examined the genome evolution and diversity of wild and cultivated landrace potatoes, which limits the application of their diversity in potato breeding. Here we assemble 44 high-quality diploid potato genomes from 24 wild and 20 cultivated accessions that are representative of Solanum section Petota, the tuber-bearing clade, as well as 2 genomes from the neighbouring section, Etuberosum. Extensive discordance of phylogenomic relationships suggests the complexity of potato evolution. We find that the potato genome substantially expanded its repertoire of disease-resistance genes when compared with closely related seed-propagated solanaceous crops, indicative of the effect of tuber-based propagation strategies on the evolution of the potato genome. We discover a transcription factor that determines tuber identity and interacts with the mobile tuberization inductive signal SP6A. We also identify 561,433 high-confidence structural variants and construct a map of large inversions, which provides insights for improving inbred lines and precluding potential linkage drag, as exemplified by a 5.8-Mb inversion that is associated with carotenoid content in tubers. This study will accelerate hybrid potato breeding and enrich our understanding of the evolution and biology of potato as a global staple food crop.

Adaptive and maladaptive introgression in grapevine domestication.

Domesticated grapevines spread to Europe around 3,000 years ago. Previous studies have revealed genomic signals of introgression from wild to cultivated grapes in Europe, but the time, mode, genomic pattern, and biological effects of these introgression events have not been investigated. Here, we studied resequencing data from 345 samples spanning the distributional range of wild (Vitis vinifera ssp. sylvestris) and cultivated (V. vinifera ssp. vinifera) grapes. Based on machine learning-based population genetic analyses, we detected evidence for a single domestication of grapevine, followed by continuous gene flow between European wild grapes (EU) and cultivated grapes over the past ~2,000 y, especially from EU to wine grapes. We also inferred that soft-selective sweeps were the dominant signals of artificial selection. Gene pathways associated with the synthesis of aromatic compounds were enriched in regions that were both selected and introgressed, suggesting EU wild grapes were an important resource for improving the flavor of cultivated grapes. Despite the potential benefits of introgression in grape improvement, the introgressed fragments introduced a higher deleterious burden, with most deleterious SNPs and structural variants hidden in a heterozygous state. Cultivated wine grapes have benefited from adaptive introgression with wild grapes, but introgression has also increased the genetic load. In general, our study of beneficial and harmful effects of introgression is critical for genomic breeding of grapevine to take advantage of wild resources.

Genomic conservation of crop wild relatives: A case study of citrus.

Conservation of crop wild relatives is critical for plant breeding and food security. The lack of clarity on the genetic factors that lead to endangered status or extinction create difficulties when attempting to develop concrete recommendations for conserving a citrus wild relative: the wild relatives of crops. Here, we evaluate the conservation of wild kumquat (Fortunella hindsii) using genomic, geographical, environmental, and phenotypic data, and forward simulations. Genome resequencing data from 73 accessions from the Fortunella genus were combined to investigate population structure, demography, inbreeding, introgression, and genetic load. Population structure was correlated with reproductive type (i.e., sexual and apomictic) and with a significant differentiation within the sexually reproducing population. The effective population size for one of the sexually reproducing subpopulations has recently declined to ~1,000, resulting in high levels of inbreeding. In particular, we found that 58% of the ecological niche overlapped between wild and cultivated populations and that there was extensive introgression into wild samples from cultivated populations. Interestingly, the introgression pattern and accumulation of genetic load may be influenced by the type of reproduction. In wild apomictic samples, the introgressed regions were primarily heterozygous, and genome-wide deleterious variants were hidden in the heterozygous state. In contrast, wild sexually reproducing samples carried a higher recessive deleterious burden. Furthermore, we also found that sexually reproducing samples were self-incompatible, which prevented the reduction of genetic diversity by selfing. Our population genomic analyses provide specific recommendations for distinct reproductive types and monitoring during conservation. This study highlights the genomic landscape of a wild relative of citrus and provides recommendations for the conservation of crop wild relatives.

Population comparative genomics discovers gene gain and loss during grapevine domestication.

Plant domestication are evolutionary experiments conducted by early farmers since thousands years ago, during which the crop wild progenitors are artificially selected for desired agronomic traits along with dramatic genomic variation in the course of moderate to severe bottlenecks. However, previous investigations are mainly focused on small-effect variants, while changes in gene contents are rarely investigated due to the lack of population-level assemblies for both the crop and its wild relatives. Here, we applied comparative genomic analyses to discover gene gain and loss during grapevine domestication using long-read assemblies of representative population samples for both domesticated grapevines (V. vinifera ssp. vinifera) and their wild progenitors (V. vinifera ssp. sylvestris). Only ∼7% of gene families were shared by 16 Vitis genomes while ∼8% of gene families were specific to each accession, suggesting dramatic variations of gene contents in grapevine genomes. Compared to wild progenitors, the domesticated accessions exhibited an increased presence of genes associated with asexual reproduction, while the wild progenitors showcased a higher abundance of genes related to pollination, revealing the transition from sexual reproduction to clonal propagation during domestication processes. Moreover, the domesticated accessions harbored fewer disease-resistance genes than wild progenitors. The SVs occurred frequently in aroma and disease-resistance related genes between domesticated grapevines and wild progenitors, indicating the rapid diversification of these genes during domestication. Our study provides insights and resources for biological studies and breeding programs in grapevine.

Phased telomere-to-telomere reference genome and pangenome reveal an expansion of resistance genes during apple domestication.

The cultivated apple (Malus domestica Borkh.) is a cross-pollinated perennial fruit tree of great economic importance. Earlier versions of apple reference genomes were unphased, fragmented, and lacked comprehensive insights into the apple's highly heterozygous genome, which impeded advances in genetic studies and breeding programs. In this study, we assembled a haplotype-resolved telomere-to-telomere (T2T) reference genome for the diploid apple cultivar Golden Delicious. Subsequently, we constructed a pangenome based on 12 assemblies from wild and cultivated species to investigate the dynamic changes of functional genes. Our results revealed the gene gain and loss events during apple domestication. Compared with cultivated species, more gene families in wild species were significantly enriched in oxidative phosphorylation, pentose metabolic process, responses to salt, and abscisic acid biosynthesis process. Our analyses also demonstrated a higher prevalence of different types of resistance gene analogs (RGAs) in cultivars than their wild relatives, partially attributed to segmental and tandem duplication events in certain RGAs classes. Structural variations, mainly deletions and insertions, have affected the presence and absence of TIR-NB-ARC-LRR, NB-ARC-LRR, and CC-NB-ARC-LRR genes. Additionally, hybridization/introgression from wild species has also contributed to the expansion of resistance genes in domesticated apples. Our haplotype-resolved T2T genome and pangenome provide important resources for genetic studies of apples, emphasizing the need to study the evolutionary mechanisms of resistance genes in apple breeding.

A rice variation map derived from 10 548 rice accessions reveals the importance of rare variants.

Detailed knowledge of the genetic variations in diverse crop populations forms the basis for genetic crop improvement and gene functional studies. In the present study, we analyzed a large rice population with a total of 10 548 accessions to construct a rice super-population variation map (RSPVM), consisting of 54 378 986 single nucleotide polymorphisms, 11 119 947 insertion/deletion mutations and 184 736 presence/absence variations. Assessment of variation detection efficiency for different population sizes revealed a sharp increase of all types of variation as the population size increased and a gradual saturation of that after the population size reached 10 000. Variant frequency analysis indicated that ∼90% of the obtained variants were rare, and would therefore likely be difficult to detect in a relatively small population. Among the rare variants, only 2.7% were predicted to be deleterious. Population structure, genetic diversity and gene functional polymorphism of this large population were evaluated based on different subsets of RSPVM, demonstrating the great potential of RSPVM for use in downstream applications. Our study provides both a rich genetic basis for understanding natural rice variations and a powerful tool for exploiting great potential of rare variants in future rice research, including population genetics and functional genomics.

Pan-mitogenomics reveals the genetic basis of cytonuclear conflicts in citrus hybridization, domestication, and diversification.

Although interactions between the cytoplasmic and nuclear genomes occurred during diversification of many plants, the evolutionary conflicts due to cytonuclear interactions are poorly understood in crop breeding. Here, we constructed a pan-mitogenome and identified chimeric open reading frames (ORFs) generated by extensive structural variations (SVs). Meanwhile, short reads from 184 accessions of citrus species were combined to construct three variation maps for the nuclear, mitochondrial, and chloroplast genomes. The population genomic data showed discordant topologies between the cytoplasmic and nuclear genomes because of differences in mutation rates and levels of heteroplasmy from paternal leakage. An analysis of species-specific SVs indicated that mitochondrial heteroplasmy was common and that chloroplast heteroplasmy was undetectable. Interestingly, we found a prominent divergence in the mitogenomes and the highest genetic load in the, which may provide the basis for cytoplasmic male sterility (CMS) and thus influence the reshuffling of the cytoplasmic and nuclear genomes during hybridization. Using cytoplasmic replacement experiments, we identified a type of species-specific CMS in mandarin related to two chimeric mitochondrial genes. Our analyses indicate that cytoplasmic genomes from mandarin have rarely been maintained in hybrids and that paternal leakage produced very low levels of mitochondrial heteroplasmy in mandarin. A genome-wide association study (GWAS) provided evidence for three nuclear genes that encode pentatricopeptide repeat (PPR) proteins contributing to the cytonuclear interactions in the Citrus genus. Our study demonstrates the occurrence of evolutionary conflicts between cytoplasmic and nuclear genomes in citrus and has important implications for genetics and breeding.

Quasi-One-Dimensional Zigzag Covalent Organic Frameworks for Photocatalytic Hydrogen Evolution from Water.

Covalent organic frameworks (COFs) have potential applications in a wide range of fields. However, it remains a critical challenge to constrain their covalent expansions in the one-dimensional (1D) direction. Here, we developed a general approach to fabricate 15 different highly crystalline COFs with zigzag-packed 1D porous organic chains through the condensation of V-shaped ditopic linkers and X-shaped tetratopic knots. Appropriate geometrical combinations of a wide scope of linkers and knots with distinct aromatic cores, linkages, and functionalities offer a series of quasi-1D COFs with dominant pore sizes of 7-13 Å and surface areas of 116-784 m2 g-1. Among them, nitrogen (N)-doped 1D COFs with site-specific doping of heteroatoms favor a tunable control of band structures and conjugations and thus allow a remarkable hydrogen evolution rate up to 80 mmol g-1 h-1 in photocatalytic water splitting. This general strategy toward programming function in porous crystalline materials has the potential to tune the topologically well-defined electronic properties through precisely periodic doping.

Surface Engineering of Nanoparticles toward Cancer Theranostics.

Development of multifunctional nanoparticles (NPs) with desired properties is a significant topic in the field of nanotechnology and has been anticipated to revolutionize cancer diagnosis and treatment modalities. The surface character is one of the most important parameters of NPs that can directly affect their in vivo fate, bioavailability, and final theranostic outcomes and thus should be carefully tuned to maximize the diagnosis and treatment effects while minimizing unwanted side effects. Surface engineered NPs have utilized various surface functionality types and approaches to meet the requirements of cancer therapy and imaging. Despite the various strategies, these surface modifications generally serve similar purposes, namely, introducing therapeutic/imaging modules, improving stability and circulation, enhancing targeting ability, and achieving controlled functions. These surface engineered NPs hence could be applied in various cancer diagnosis and treatment scenarios and continuously contribute to the clinical translation of the next-generation NP-based platforms toward cancer theranostics.In this Account, we present recent advances and research efforts on the development of NP surface engineering toward cancer theranostics. First, we summarize the general strategies for NP surface engineering. Various types of surface functionalities have been applied including inorganic material-based functionality, organic material-based functionality like small molecules, polymers, nucleic acids, peptides, proteins, carbohydrates, antibodies, etc., and biomembrane-based functionality. These surface modifications can be realized by prefabrication or postfabrication functionalization, driven by covalent conjugations or noncovalent interactions. Second, we highlight the general aims of these different NPs surface functionalities. Different therapeutic and diagnostic modules, such as nanozymes, antibodies, and imaging contrast agents, have been modified on the surface of NPs to achieve theranostic function. Surface modification also can improve stability and circulation of NPs by protecting the NPs from immune recognition and clearance. In addition, to achieve targeted therapy and imaging, various targeting moieties have been attached on the NP surface to enhance active targeting ability to tissues or cells of interest. Furthermore, the NP surfaces can be tailored to achieve controlled functions which only respond to specific internal (e.g., pH, thermal, redox, enzyme, hypoxia) or external (e.g., light, ultrasound) triggers at the precise action sites. Finally, we present our perspective on the remaining challenges and future developments in this significant and rapidly evolving field. We hope this Account can offer an insightful overlook on the recent progress and an illuminating prospect on the advanced strategies, promoting more attention in this area and adoption by more scientists in various research fields, accelerating the development of NP surface engineering with a solid foundation and broad cancer theranostics applications.