Meiotic recombination plays a crucial role in the generation of new varieties. The effectiveness of recombination is limited by the distribution of crossover events, which in wheat and many other crops is skewed toward the distal regions of the chromosomes. Whole-genome sequencing of wheat has revealed that there are numerous important genes in the pericentromeric regions, which are inaccessible to manipulation due to the lack of crossover events. Studies in barley have shown that the distribution of recombination events can be shifted toward the centromeres by increasing temperature during meiosis. Here we present an analysis of the effects of temperature on the distribution and frequency of recombination events in wheat. Our data show that although increased temperature during meiosis does cause an inward shift in recombination distribution for some chromosomes, its overall utility is limited, with many genes remaining highly linked.

Understanding the evolutionary pathways to metastasis and resistance to immune checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here we present the most comprehensive intra-patient metastatic melanoma dataset assembled to date as part of the PEACE research autopsy programme, including 222 exome, 493 panel-sequenced, 161 RNA-seq, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI non-responders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one of the patients. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.

Segregation distortion is the phenomenon in which genotypes deviate from expected Mendelian ratios in the progeny of a cross between two varieties or species. There is not currently a widely used consensus for the appropriate statistical test, or more specifically the multiple testing correction procedure, used to detect segregation distortion for high-density single-nucleotide polymorphism (SNP) data. Here we examine the efficacy of various multiple testing procedures, including chi-square test with no correction for multiple testing, falsediscovery rate correction and Bonferroni correction using an in-silico simulation of a biparental mapping population. We find that the false discovery rate correction best approximates the traditional p-value threshold of 0.05 for high-density marker data. We also utilize this simulation to test the effect of segregation distortion on the genetic mapping process, specifically on the formation of linkage groups during marker clustering. Only extreme segregation distortion was found to effect genetic mapping. In addition, we utilize replicate empirical mapping populations of wheat varieties Avalon and Cadenza to assess how often segregation distortion conforms to the same pattern between closely related wheat varieties.

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<p><b>A,</b> Phylogenies inferred for the 14 patients. Only WES samples are included. Letters in brackets indicate melanoma subtype: A = acral, C = cutaneous, M = mucosal, U = melanoma of unknown primary. Branch length is proportional to the number of mutations. Branch colors represent the mutational signatures of the mutations. For clarity, only the most common mutational signatures are shown; the remainder are categorized as “unknown.” Scale bars indicate the number of mutations. The legend includes etiologies for each signature (<a href="#bib24" target="_blank">24</a>). MMR, mismatch repair. <b>B,</b> Boxplots indicate the ratio of subclonal mutations (length of branches) to clonal mutations (length of the trunk) by subtype and chemotherapy status. Values smaller than zero indicate the dominance of truncal mutations. Mann–Whitney <i>U</i> test was used for statistical comparisons (**, <i>P</i> < 0.01; ***, <i>P</i> < 0.001). Cut., cutaneous; mut., mutation.</p>