Variation in human complex traits is connected to variation in gene expression, and selection on complex traits can be reflected in selection on gene expression. Here, Glassberg and Gao et al. analyze polymorphic....

Women are under-represented in science, technology, engineering, and mathematics (STEM). Despite the recent emphasis on diversity in STEM, our understanding of what drives differences between women and men scientists remains limited. This, in turn, limits our ability to intervene to level the playing field. To quantify the representation and participation of women and men at academic meetings in human genetics, we developed high-throughput and crowd-sourced approaches focused on question-asking behavior. Question asking is one voluntary and self-initiated scientific activity we can measure. Here we report that women ask fewer questions than expected regardless of their representation in talk audiences. We present evidence that external barriers affect the representation of women in STEM. However, differences in question-asking behavior suggest that internal factors also impact women's participation. We then examine the effects of specific interventions and show that wide public discussion of the relative under-participation of women in question-and-answer sessions alters question-asking behavior. We suggest that engaging the community in such projects promotes visibility of diversity issues at academic meetings and allows for efficient data collection that can be used to further explore and understand differences in conference participation.

Within-host adaptation of pathogens such as human immunodeficiency virus (HIV) often occurs at more than two loci. Multiple beneficial mutations may arise simultaneously on different genetic backgrounds and interfere, affecting each other's fixation trajectories. Here, we explore how these evolutionary dynamics are mirrored in multilocus linkage disequilibrium (MLD), a measure of multi-way associations between alleles. In the parameter regime corresponding to HIV, we show that deterministic early infection models induce MLD to oscillate over time in a wavelet-like fashion. We find that the frequency of these oscillations is proportional to the rate of adaptation. This signature is robust to drift, but can be eroded by high variation in fitness effects of beneficial mutations. Our findings suggest that MLD oscillations could be used as a signature of interference among multiple equally advantageous mutations and may aid the interpretation of MLD in data.

Gene expression variation is a major contributor to phenotypic variation in human complex traits. Selection on complex traits may therefore be reflected in constraint on gene expression levels. Here, we explore the effects of stabilizing selection on cisregulatory genetic variation in humans. We analyze patterns of expression variation at copy number variants and find evidence for selection against large increases in gene expression. Using allele-specific expression (ASE) data, we further show evidence of selection against smaller-effect variants. We estimate that, across all genes, singletons in a sample of 122 individuals have approximately 2.5× greater effects on expression variance than common variants. Despite their increased effect sizes relative to common variants, we estimate that singletons in the sample studied explain, on average, only 5% of the heritability of gene expression from cis-regulatory variants. Finally, we show that genes depleted for loss-of-function variants are also depleted for cis-eQTLs and have low levels of allelic imbalance, confirming tighter constraint on the expression levels of these genes. We conclude that constraint on gene expression is present, but has relatively weak effects on most cis-regulatory variants, thus permitting high levels of gene-regulatory genetic variation. Gene expression|Allele-specific expression|Stabilizing selection|Heritability IntroductionVariation in human complex traits is connected to variation in gene expression levels (1-7). Selection on complex traits (i.e. complex disease) may therefore be reflected in selection on gene expression. Across species, gene expression levels have been shown to evolve more slowly than would be expected under a neutral model (8)(9)(10)(11)). An analysis of mammalian gene duplications also showed that the total expression of gene pairs in species that experienced a duplication event is similar to the expression of the corresponding single gene copy in species without duplication (12). As a duplication event would be expected to dramatically increase gene expression, this observation suggests that stabilizing selection on gene expression may act to return the total expression of duplicate gene pairs to an optimal expression level. Constraint on gene expression levels has also been shown to influence patterns of genetic variation within humans. First, 1 Correspondence: pritch@stanford.edu 2 ECG and ZG contributed equally to this work. some genes are unusually depleted for loss-of-function and copy number variants (13,14). These genes are thought to be particularly constrained with respect to their expression. Further, individuals with extreme expression levels for a particular gene are more likely to have rare variants in cis than individuals with average expression levels (15-18), suggesting that large gene expression changes are associated with rare genetic variation. As detailed below, this observation is consistent with stabilizing selection on expression levels selecting against large-effect regulatory variants. Des...

With increasing awareness that women in science have often been underrecognized for their research, a variety of efforts have sought to recover and highlight past contributions of female scientists, including in TPB-related fields (e.g. Wellenreuther & Otto 2016;Bronstein & Bolnick 2018). A recent commentary turns the focus of one such effort specifically to Theoretical Population Biology, providing important recognition to the role of female programmers in TPB papers from 1970 to 1990(Dung et al. 2019.Writing in Genetics, Dung et al. observed that authors of early papers in TPB frequently acknowledged computer programmers for assistance. Among the programmers for whom they were able to assign a gender, they found that 43.2% were female, a substantially larger fraction than the 7.4% of gender-identifiable TPB authors in the same period who were female.Based on the text acknowledging the programmers, Dung et al. commented that many of the tasks performed by programmers involved significant contributions, including development of statistical algorithms, programming of simulations, and sophisticated numerical analyses -roles that would likely result in authorship under current practice. Several of the programmers appear in acknowledgments of multiple papers, having contributed to a body of work in TPB reported over a period of several years.

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