Genetic ancestry, differential gene expression, and survival in pediatric B-cell acute lymphoblastic leukemia.

BACKGROUND: Black children have lower incidence yet worse survival than White and Latinx children with B-cell acute lymphoblastic leukemia (B-ALL). It is unclear how reported race/ethnicity (RRE) is associated with death in B-ALL after accounting for differentially expressed genes associated with genetic ancestry. METHODS: Using Phase 1 and 2 NCI TARGET B-ALL cases (N = 273; RRE-Black = 21, RRE-White = 162, RRE-Latinx = 69, RRE-Other = 9, RRE-Unknown = 12), we estimated proportions of African (AFR), European (EUR), and Amerindian (AMR) genetic ancestry. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) between ancestry and death while adjusting for RRE and clinical measures. We identified genes associated with genetic ancestry and adjusted for them in RRE and death associations. RESULTS: Genetic ancestry varied within RRE (RRE-Black, AFR proportion: Mean: 78.5%, Range: 38.2%-93.6%; RRE-White, EUR proportion: Mean: 94%, Range: 1.6%-99.9%; RRE-Latinx, AMR proportion: Mean: 52.0%, Range: 1.2%-98.7%). We identified 10, 1, and 6 differentially expressed genes (padjusted  <0.05) associated with AFR, AMR, and EUR ancestry proportion, respectively. We found AMR and AFR ancestry were statistically significantly associated with death (AMR each 10% HR: 1.05, 95% CI: 1.03-1.17, AFR each 10% increase HR: 1.03, 95% CI:1.01-1.19). RRE differences in the risk of death were larger in magnitude upon adjustment for genes associated with genetic ancestry for RRE-Black, but not RRE-Latinx children (RRE-Black HR: 3.35, 95% CI: 1.31, 8.53; RRE-Latinx HR: 1.47, 0.88-2.45). CONCLUSIONS: Our work highlights B-ALL survival differences by RRE after adjusting for ancestry differentially expressed genes suggesting other factors impacting survival are important.

Development of first linkage map for Silphium integrifolium (Asteraceae) enables identification of sporophytic self-incompatibility locus.

Silphium integrifolium (Asteraceae) has been identified as a candidate for domestication as a perennial oilseed crop and is assumed to have sporophytic self-incompatibility system-the genetic basis of which is not well understood in the Asteraceae. To address this gap, we sought to map the genomic location of the self-recognition locus (S-locus) in this species. We used a biparental population and genotyping-by-sequencing to create the first genetic linkage map for this species, which contained 198 SNP markers and resolved into the correct number of linkage groups. Then we developed a novel crossing scheme and set of analysis methods in order to infer S-locus genotypes for a subset of these individuals, allowing us to map the trait. Finally, we evaluated potential genes of interest using synteny analysis with the annual sunflower (Helianthus annuus) and lettuce (Lactuca sativa) genomes. Our results confirm that S. integrifolium does indeed have a sporophytic self-incompatibility system. Our method is effective and efficient, allowed us to map the S. integrifolium S-locus using fewer resources than existing methods, and could be readily applied to other species.

Biosystematic studies on the status of Solanum chilense.

PREMISE: Common taxonomic practices, which condition species' descriptions on diagnostic morphological traits, may systematically lump outcrossing species and unduly split selfing species. Specifically, higher effective population sizes and genetic diversity of obligate outcrossers are expected to result less reliable phenotypic diagnoses. Wild tomatoes, members of Solanum sect. Lycopersicum, are commonly used as a source of exotic germplasm for improvement of the cultivated tomato, and are increasingly employed in basic research. Although the section experienced significant early work, which continues presently, the taxonomic status of many wild species has undergone a number of significant revisions and remains uncertain. Species in this section vary in their breeding systems, notably the expression of self-incompatibility, which determines individual propensity for outcrossing METHODS: Here, we examine the taxonomic status of obligately outcrossing Chilean wild tomato (Solanum chilense) using reduced-representation sequencing (RAD-seq), a range of phylogenetic and population genetic analyses, as well as analyses of crossing and morphological data. RESULTS: Overall, each of our analyses provides a considerable weight of evidence that the Pacific coastal populations and Andean inland populations of the currently described Solanum chilense represent separately evolving populations, and conceal at least one undescribed cryptic species. CONCLUSIONS: Despite its vast economic importance, Solanum sect. Lycopersicon still exhibits considerable taxonomic instability. A pattern of under-recognition of outcrossing species may be common, not only in tomatoes, but across flowering plants. We discuss the possible causes and implications of this observation, with a focus on macroevolutionary inference.

Patterns of genetic variation in a prairie wildflower, Silphium integrifolium, suggest a non-prairie origin and locally adaptive variation.

PREMISE: Understanding the relationship between genetic structure and geography provides information about a species' history and can be used for breeding and conservation goals. The North American prairie is interesting because of its recent origin and subsequent fragmentation. Silphium integrifolium, an iconic perennial American prairie wildflower, is targeted for domestication, having undergone a few generations of improvement. We present the first application of population genetic data in this species to address the following goals: (1) improve breeding by characterizing genetic structure and (2) identify the species geographic origin and potential targets and drivers of selection during range expansion. METHODS: We developed a reference transcriptome as a genotyping reference for samples from throughout the species range. Population genetic analyses were used to describe patterns of genetic variation, and demographic modeling was used to characterize potential processes that shaped variation. Outlier scans for selection and associations with environmental variables were used to identify loci linked to putative targets and drivers of selection. RESULTS: Genetic variation partitioned samples into three geographic clusters. Patterns of variation and demographic modeling suggest that the species origin is in the American Southeast. Breeding program accessions are from the region with lowest observed genetic variation. CONCLUSIONS: This prairie species did not originate within the prairie. Breeding may be improved by including accessions from outside of the germplasm founding region. The geographic structuring and the identified targets and drivers of adaptation can guide collecting efforts toward populations with beneficial agronomic traits.

The expression of self-incompatibility in angiosperms is bimodal.

Self-incompatibility is expressed by nearly one-half of all angiosperms. A large proportion of the remaining species are self-compatible, and they either outcross using various contrivances or self-fertilize to some extent. Because of the common occurrence of populations and individuals with intermediate levels of self-incompatibility, categorization of the expression of self-incompatibility as an approximately binary trait has become controversial. We collect a widely reported index (index of self-incompatibility [ISI]) used to asses the strength and variation of self-incompatibility from over 1200 angiosperm taxa. Its distribution is bimodal and positively associated with outcrossing rate, albeit with a weak relationship within self-compatible taxa. A substantial fraction of species has intermediate mean values of ISI. Their occurrence can be caused by segregating ephemeral self-compatible mutations, averaging artifacts, and experimental biases, in addition to the often invoked stabilizing selection acting on the expression of self-incompatibility. Selection may also generally favor taxa with high ISI values through increased lineage birth and death rates, and it may counter lower level selection advantages within taxa expressing intermediate and low values of ISI. Such a null hypothesis is nearly universally overlooked, despite the fact that it could adequately explain the observed distribution of mating and breeding systems.

Effective population size is positively correlated with levels of adaptive divergence among annual sunflowers.

The role of adaptation in the divergence of lineages has long been a central question in evolutionary biology, and as multilocus sequence data sets have become available for a wide range of taxa, empirical estimates of levels of adaptive molecular evolution are increasingly common. Estimates vary widely among taxa, with high levels of adaptive evolution in Drosophila, bacteria, and viruses but very little evidence of widespread adaptive evolution in hominids. Although estimates in plants are more limited, some recent work has suggested that rates of adaptive evolution in a range of plant taxa are surprisingly low and that there is little association between adaptive evolution and effective population size in contrast to patterns seen in other taxa. Here, we analyze data from 35 loci for six sunflower species that vary dramatically in effective population size. We find that rates of adaptive evolution are positively correlated with effective population size in these species, with a significant fraction of amino acid substitutions driven by positive selection in the species with the largest effective population sizes but little or no evidence of adaptive evolution in species with smaller effective population sizes. Although other factors likely contribute as well, in sunflowers effective population size appears to be an important determinant of rates of adaptive evolution.

Contributions of flowering time genes to sunflower domestication and improvement.

Determining the identity and distribution of molecular changes leading to the evolution of modern crop species provides major insights into the timing and nature of historical forces involved in rapid phenotypic evolution. In this study, we employed an integrated candidate gene strategy to identify loci involved in the evolution of flowering time during early domestication and modern improvement of the sunflower (Helianthus annuus). Sunflower homologs of many genes with known functions in flowering time were isolated and cataloged. Then, colocalization with previously mapped quantitative trait loci (QTLs), expression, or protein sequence differences between wild and domesticated sunflower, and molecular evolutionary signatures of selective sweeps were applied as step-wise criteria for narrowing down an original pool of 30 candidates. This process led to the discovery that five paralogs in the flowering locus T/terminal flower 1 gene family experienced selective sweeps during the evolution of cultivated sunflower and may be the causal loci underlying flowering time QTLs. Our findings suggest that gene duplication fosters evolutionary innovation and that natural variation in both coding and regulatory sequences of these paralogs responded to a complex history of artificial selection on flowering time during the evolution of cultivated sunflower.

Effective population size, gene flow, and species status in a narrow endemic sunflower, Helianthus neglectus, compared to its widespread sister species, H. petiolaris.

Species delimitation has long been a difficult and controversial process, and different operational criteria often lead to different results. In particular, investigators using phenotypic vs. molecular data to delineate species may recognize different boundaries, especially if morphologically or ecologically differentiated populations have only recently diverged. Here we examine the genetic relationship between the widespread sunflower species Helianthus petiolaris and its narrowly distributed sand dune endemic sister species H. neglectus using sequence data from nine nuclear loci. The two species were initially described as distinct based on a number of minor morphological differences, somewhat different ecological tolerances, and at least one chromosomal rearrangement distinguishing them; but detailed molecular data has not been available until now. We find that, consistent with previous work, H. petiolaris is exceptionally genetically diverse. Surprisingly, H. neglectus harbors very similar levels of genetic diversity (average diversity across loci is actually slightly higher in H. neglectus). It is extremely unlikely that such a geographically restricted species could maintain these levels of genetic variation in isolation. In addition, the two species show very little evidence of any genetic divergence, and estimates of interspecific gene flow are comparable to gene flow estimates among regions within H. petiolaris. These results indicate that H. petiolaris and H. neglectus likely do not represent two distinct, isolated gene pools; H. neglectus is probably more accurately thought of as a geographically restricted, morphologically and ecologically distinct subspecies of H. petiolaris rather than a separate species.

The role of recently derived FT paralogs in sunflower domestication.

Gene duplication provides an important source of genetic raw material for phenotypic diversification, but few studies have detailed the mechanisms through which duplications produce evolutionary novelty within species. Here, we investigate how a set of recently duplicated homologs of the floral inducer FLOWERING LOCUS T (FT) has contributed to sunflower domestication. We find that changes in expression of these duplicates are associated with differences in flowering behavior between wild and domesticated sunflower. In addition, we present genetic and functional evidence demonstrating that a frameshift mutation in one paralog, Helianthus annuus FT 1 (HaFT1), underlies a major QTL for flowering time and experienced a selective sweep during early domestication. Notably, this dominant-negative allele delays flowering through interference with action of another paralog, HaFT4. Together, these data reveal that changes affecting the expression, sequence, and gene interactions of HaFT paralogs have played key roles during sunflower domestication. Our findings also illustrate the important role that evolving interactions between new gene family members may play in fostering phenotypic change.