Genomic analysis of a major seed protein/oil QTL region on soybean linkage group I

The economic and nutritional value of soybeans is determined by its seed protein and oil contents. The genetic control of seed protein/oil is quantitative and many genomic regions associated with the regulation of these traits have been identified in soybean. The protein/oil quantitative trait locus (QTL) mapped to LG I (chromosome 20) is ubiquitous among high protein soybean lines. Identification of the candidate gene(s) underlying this major QTL would help us understand the genetic and molecular mechanisms regulating seed protein/oil accumulation in soybean. Map based cloning to identify the candidate genes for the LG I QTL was undertaken. A BAC based physical map of the region was developed by chromosome walking. Utilizing the genome sequence of soybean and the fine genetic mapping, the QTL region was delineated to an approximately 8.4 Mbp pericentromeric region on chromosome 20. Thirteen genes exhibiting differential expression in developing seeds of near isogenic-lines (NILs) contrasting in protein/oil contents, were identified as potential candidates for the QTL. The homoeologous region corresponding to the QTL region was identified on chromosome 10, spanning a 7.3 Mbp pericentromeric region. Evidence suggests these regions were products of the recent soybean genome duplication 10-14 million years ago (MYA). Comparative analysis of the two regions indicated that both regions are hot spots for retrotransposon accumulation. However, the chromosome 20 region showed preferential accumulation of retrotransposons. The extent of synteny was poor in the retrotransposon rich (gene poor) regions while the adjacent retrotransposon poor (gene rich) regions showed high levels of synteny and colinearity. The genes conserved across the regions showed evidence of sub-funtionalization. The conserved genes were evolving under purifying selection and were enriched for genes involved in stress responses and transcription regulation. The abundance of retrotransposons in these regions points to the likely role of retrotransposons in the evolution of these regions. A detailed study of the retrotransposon insertions in BAC-sized regions around the QTL indicated intergenic and intragenic insertions. The majority of retrotransposon accumulations in the regions studied, happened in the past two million years. Retrotransposon insertions and selection against the insertions could be the predominant forces driving the evolution of this major protein/oil QTL region in soybean

Genomics of Evolutionary Novelty in Hybrids and Polyploids

It has long been recognized that hybridization and polyploidy are prominent processes in plant evolution. Although classically recognized as significant in speciation and adaptation, recognition of the importance of interspecific gene flow has dramatically increased during the genomics era, concomitant with an unending flood of empirical examples, with or without genome doubling. Interspecific gene flow is thus increasingly thought to lead to evolutionary innovation and diversification, via adaptive introgression, homoploid hybrid speciation and allopolyploid speciation. Less well understood, however, are the suite of genetic and genomic mechanisms set in motion by the merger of differentiated genomes, and the temporal scale over which recombinational complexity mediated by gene flow might be expressed and exposed to natural selection. We focus on these issues here, considering the types of molecular genetic and genomic processes that might be set in motion by the saltational event of genome merger between two diverged species, either with or without genome doubling, and how these various processes can contribute to novel phenotypes. Genetic mechanisms include the infusion of new alleles and the genesis of novel structural variation including translocations and inversions, homoeologous exchanges, transposable element mobilization and novel insertional effects, presence-absence variation and copy number variation. Polyploidy generates massive transcriptomic and regulatory alteration, presumably set in motion by disrupted stoichiometries of regulatory factors, small RNAs and other genome interactions that cascade from single-gene expression change up through entire networks of transformed regulatory modules. We highlight both these novel combinatorial possibilities and the range of temporal scales over which such complexity might be generated, and thus exposed to natural selection and drift

Cytonuclear interactions remain stable during allopolyploid evolution despite repeated whole-genome duplications in Brassica

Several plastid macromolecular protein complexes are encoded by both nuclear and plastid genes. Therefore, cytonuclear interactions are held in place to prevent genomic conflicts that may lead to incompatibilities. Allopolyploidy resulting from hybridization and genome doubling of two divergent species can disrupt these fine-tuned interactions, as newly formed allopolyploid species confront biparental nuclear chromosomes with a uniparentally inherited plastid genome. To avoid any deleterious effects of unequal genome inheritance, preferential transcription of the plastid donor over the other donor has been hypothesized to occur in allopolyploids. We used Brassica as a model to study the effects of paleopolyploidy in diploid parental species, as well as the effects of recent and ancient allopolyploidy in Brassica napus, on genes implicated in plastid protein complexes. We first identified redundant nuclear copies involved in those complexes. Compared with cytosolic protein complexes and with genome-wide retention rates, genes involved in plastid protein complexes show a higher retention of genes in duplicated and triplicated copies. Those redundant copies are functional and are undergoing strong purifying selection. We then compared transcription patterns and sequences of those redundant gene copies between resynthesized allopolyploids and their diploid parents. The neopolyploids showed no biased subgenome expression or maternal homogenization via gene conversion, despite the presence of some non-synonymous substitutions between plastid genomes of parental progenitors. Instead, subgenome dominance was observed regardless of the maternal progenitor. Our results provide new insights on the evolution of plastid protein complexes that could be tested and generalized in other allopolyploid species

Occurrence and implicatons of biological network evolution following polyploidy

The mapping and comparison of biological networks allows for analysis to understand forces of evolution. Here, we synthesize information about polyploidy, or whole genome duplication, and its effects on network rewiring. Network changes may have lead to the diversity and survival of some lineages of life, and by understanding network evolution, we may discover patterns that explain how organisms evolve. Specifically, we focus on the consequences of polyploidy on flowering time. Our work aids those studying different aspects of polyploidy to see a bigger picture of how it contributes to evolutionary change and important features that may be involved in cancer. Future studies of biological networks will help improve models of disease and biological processes to make better crops for food, fuel, fiber, and pharmaceuticals

Evolution of Stress-Regulated Gene Expression in Duplicate Genes of Arabidopsis thaliana

Due to the selection pressure imposed by highly variable environmental conditions, stress sensing and regulatory response mechanisms in plants are expected to evolve rapidly. One potential source of innovation in plant stress response mechanisms is gene duplication. In this study, we examined the evolution of stress-regulated gene expression among duplicated genes in the model plant Arabidopsis thaliana. Key to this analysis was reconstructing the putative ancestral stress regulation pattern. By comparing the expression patterns of duplicated genes with the patterns of their ancestors, duplicated genes likely lost and gained stress responses at a rapid rate initially, but the rate is close to zero when the synonymous substitution rate (a proxy for time) is >∼0.8. When considering duplicated gene pairs, we found that partitioning of putative ancestral stress responses occurred more frequently compared to cases of parallel retention and loss. Furthermore, the pattern of stress response partitioning was extremely asymmetric. An analysis of putative cis-acting DNA regulatory elements in the promoters of the duplicated stress-regulated genes indicated that the asymmetric partitioning of ancestral stress responses are likely due, at least in part, to differential loss of DNA regulatory elements; the duplicated genes losing most of their stress responses were those that had lost more of the putative cis-acting elements. Finally, duplicate genes that lost most or all of the ancestral responses are more likely to have gained responses to other stresses. Therefore, the retention of duplicates that inherit few or no functions seems to be coupled to neofunctionalization. Taken together, our findings provide new insight into the patterns of evolutionary changes in gene stress responses after duplication and lay the foundation for testing the adaptive significance of stress regulatory changes under highly variable biotic and abiotic environments

Patient derived xenograft models of small-cell lung cancer provide molecular insights into mechanisms of chemotherapy cross-resistance

Small Cell Lung Cancer (SCLC) is a highly aggressive neuroendocrine tumor with a 5% survival rate over 5 years. Though SCLC comprises 13% of all cases of lung cancer the median survival time of 14.5 months has seen little improvement over the last four decades. Standard treatment relies on DNA damaging agents such as Cisplatin/Etoposide (EP) which induce a high response rate of 60-70%. Despite this initial response, nearly all patients will relapse rendering first-line therapies ineffective. Furthermore, SCLC has been shown to develop chemotherapy cross-resistance in which resistance to first-line chemotherapies will confer resistance to additional DNA damaging agents thereby reducing treatment efficacy and duration of response. Cross-Resistance constitutes a major clinical issue whose underlying mechanisms remain a mystery. The modest improvements in SCLC patient outcomes over the decades may be partially explained by the existing systems of study. Current methodologies of SCLC study rely on cell lines, patient samples, and Genetically Engineered Mouse Models which have little functional correlation to clinical outcomes. While few sources have proposed Patient Derived Xenograft (PDX) systems as an improved alternative, significant data remains sparse. Without a robust model system which accurately recapitulates patient outcomes, molecular pathways driving resistance cannot be uncovered. Here we present the generation of 34 SCLC PDX models which maintain both genomic and functional fidelity. Furthermore, treatment of a 30-model subset with first-line chemotherapy EP and a novel chemotherapy Olaparib/Temozolomide (OT) allowed for functional and molecular comparison between groups. Our findings demonstrate incomplete independent resistance mechanisms between EP and OT treatment with a small overlap of 31 genes involved in glycolysis and xenobiotic metabolism

Phenotypic diploidization in plant functional traits uncovered by synthetic neopolyploids in Dianthus broteri

Whole-genome duplication and post-polyploidization genome downsizing play key roles in the evolution of land plants; however, the impact of genomic diploidization on functional traits still remains poorly understood. Using Dianthus broteri as a model, we compared the ecophysiological behaviour of colchicine-induced neotetraploids (4xNeo) to diploids (2x) and naturally occurring tetraploids (4xNat). Leaf gas-exchange and chlorophyll fluorescence analyses were performed in order to asses to what extent post-polyploidization evolutionary processes have affected 4xNat. Genomic diploidization and phenotypic novelty were evident. Distinct patterns of variation revealed that post-polyploidization processes altered the phenotypic shifts directly mediated by genome doubling. The photosynthetic phenotype was affected in several ways but the main effect was phenotypic diploidization (i.e. 2x and 4xNat were closer to each other than to 4xNeo). Overall, our results show the potential benefits of considering experimentally synthetized versus naturally established polyploids when exploring the role of polyploidization in promoting functional divergence.España Ministerio de Ciencia e Innovación project POLYTRANSECO (PGC2018-098358-B-I00)Spanish Ministerio de Universidades (FPU19/02936

The evolutionary significance of polyploidy

Polyploidy, or the duplication of entire genomes, has been observed in prokaryotic and eukaryotic organisms, and in somatic and germ cells. The consequences of polyploidization are complex and variable, and they differ greatly between systems (clonal or non-clonal) and species, but the process has often been considered to be an evolutionary 'dead end'. Here, we review the accumulating evidence that correlates polyploidization with environmental change or stress, and that has led to an increased recognition of its short-term adaptive potential. In addition, we discuss how, once polyploidy has been established, the unique retention profile of duplicated genes following whole-genome duplication might explain key longer-term evolutionary transitions and a general increase in biological complexity