Individual differences in reproductive strategy are related to views about recreational drug use in Belgium, the Netherlands and Japan

Individual differences in moral views are often explained as the downstream effect of ideological commitments, such as political orientation and religiosity. Recent studies in the U.S. suggest that moral views about recreational drug use are also influenced by attitudes towards sex and that this relationship cannot be explained by ideological commitments. In this study, we investigate student samples from Belgium, the Netherlands, and Japan. We find that, in all samples, sexual attitudes are strongly related to views about recreational drug use, even after controlling for various ideological variables. We discuss our results in the light of reproductive strategies as determinants of moral views

Diversity arrays technology (DArT) markers in apple for genetic linkage maps

Diversity Arrays Technology (DArT) provides a high-throughput whole-genome genotyping platform for the detection and scoring of hundreds of polymorphic loci without any need for prior sequence information. The work presented here details the development and performance of a DArT genotyping array for apple. This is the first paper on DArT in horticultural trees. Genetic mapping of DArT markers in two mapping populations and their integration with other marker types showed that DArT is a powerful high-throughput method for obtaining accurate and reproducible marker data, despite the low cost per data point. This method appears to be suitable for aligning the genetic maps of different segregating populations. The standard complexity reduction method, based on the methylation-sensitive PstI restriction enzyme, resulted in a high frequency of markers, although there was 52–54% redundancy due to the repeated sampling of highly similar sequences. Sequencing of the marker clones showed that they are significantly enriched for low-copy, genic regions. The genome coverage using the standard method was 55–76%. For improved genome coverage, an alternative complexity reduction method was examined, which resulted in less redundancy and additional segregating markers. The DArT markers proved to be of high quality and were very suitable for genetic mapping at low cost for the apple, providing moderate genome coverage

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Genetic interests, life histories, and *attitudes towards abortion

This paper presents a behavioral ecology view of contemporary American attitudes towards the morality and legality of abortion. It is hypothesized that divergent interests in and views on the availability of abortion services are driven by zero sum competitions both between more-promiscuous and less-promiscuous reproductive strategies and between strategies that are more or less likely to limit family size in order to increase resources for children. Exploratory regression analyses are presented showing that demographic and life-history predictors that are consistent with an interest-based perspective account for a meaningful percentage of the variance in abortion attitudes in two adult samples and a large percentage of the variance in abortion attitudes in an undergraduate sample. While these analyses cannot answer difficult questions of causation, they undermine frequent claims in social science that interest-based predictors tend to work well only in limited economic domains. Additional analyses are reported calling into question views that abortion attitudes are derived from more-basic views on fetal personhood and views that political and moral attitudes generally are derived in part from more-basic positions along a single liberal-conservative ideological dimension

Genetic interests, life histories, and *attitudes towards abortion

This paper presents a behavioral ecology view of contemporary American attitudes towards the morality and legality of abortion. It is hypothesized that divergent interests in and views on the availability of abortion services are driven by zero sum competitions both between more-promiscuous and less-promiscuous reproductive strategies and between strategies that are more or less likely to limit family size in order to increase resources for children. Exploratory regression analyses are presented showing that demographic and life-history predictors that are consistent with an interest-based perspective account for a meaningful percentage of the variance in abortion attitudes in two adult samples and a large percentage of the variance in abortion attitudes in an undergraduate sample. While these analyses cannot answer difficult questions of causation, they undermine frequent claims in social science that interest-based predictors tend to work well only in limited economic domains. Additional analyses are reported calling into question views that abortion attitudes are derived from more-basic views on fetal personhood and views that political and moral attitudes generally are derived in part from more-basic positions along a single liberal-conservative ideological dimension

Sex, drugs and moral goals: reproductive strategies and views about recreational drugs

Humans, unlike most other species, show intense interest in the activities of conspecifics, even when the activities in question pose no obvious fitness threat or opportunity. Here, we investigate one content domain in which people show substantial interest, the use of drugs for non-medical purposes. Drawing from two subject populations—one undergraduate and one Internet-based—we look at the relationships among (i) abstract political commitments; (ii) attitudes about sexuality; and (iii) views surrounding recreational drugs. Whereas some theories suggest that drug views are best understood as the result of abstract political ideology, we suggest that these views can be better understood in the context of reproductive strategy. We show that, as predicted by a strategic construal, drug attitudes are best predicted by sexual items rather than abstract political commitments and, further, that the relationship between factors such as political ideology and drugs, while positive, are reduced to zero or nearly zero when items assessing sexuality are controlled for. We conclude that considering morality from the standpoint of strategic interests is a potentially useful way to understand why humans care about third party behaviour