When to Cheat: Modeling Dynamics of Paternity and Promiscuity in Socially Monogamous Prairie Voles (Microtus ochrogaster)

In many socially monogamous species, individuals form long-term pair bonds and males mate guard females. Such behavior is thought to help secure intra-pair fertilizations, the result of intra-pair copulations (IPCs), and ensure paternity. However, socially monogamous males are also often opportunistic and seek additional mating opportunities with other females, leaving their partner unguarded. The success associated with a male's decision to seek more mates over guarding his partner might be impacted by the activity of other males, specifically the proportion of other males leaving their territories to seek extra-pair copulations (EPCs). The amount of EPC-seeking males can impact the likelihood of a given male encountering an unguarded paired female, but also of being cuckolded (losing IPCs). It remains unclear under which conditions it is optimal to stay and guard or seek EPCs. Using field data from socially monogamous prairie voles (Microtus ochrogaster) to generate parameters, we used optimal performance modeling (Monte Carlo simulations) to ask when is it most reproductively advantageous for a bonded male to seek EPCs, despite the risk of losing IPCs. We defined three types of males: exclusive mating bonded males (true residents), non-exclusive mating bonded residents (roving residents), and unpaired males (wanderers). We first modeled the success of an individual male living in a context that incorporated only true and roving residents. We next added wandering males to this model. Finally, we considered the effects of including wandering males and unpaired females in our model. For all contexts, we found that as EPC-seeking in the population increases, the potential reproductive benefit for seeking EPCs increasingly outpaces the rate of cuckolding. In other words, we observe a shift in optimal strategy from true residents to rovers among paired males. Our models also demonstrate that reproductive fitness is likely to remain constant, despite the shift toward obtaining success via EPCs over IPCs. Our results show the dynamic nature of reproductive decision-making, and demonstrate that alternative reproductive decisions yield subtle but important differences despite appearing as balanced strategies

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Exercise engagement drives changes in cognition and cardiorespiratory fitness after 8 weeks of aerobic training in sedentary aging adults at risk of cognitive decline

BackgroundWith our aging population, many individuals are at risk of developing age-related cognitive decline. Physical exercise has been demonstrated to enhance cognitive performance in aging adults. This study examined the effects of 8 weeks of aerobic exercise on cognitive performance and cardiorespiratory fitness in sedentary aging adults at risk for cognitive decline.MethodsFifty-two participants (age 62.9 ± 6.8, 76.9% female) engaged in eight weeks of moderate-to high-intensity exercise (19 in-person, 33 remotely). Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status, the Delis-Kaplan Executive Function System, and the Digit Span subtest of the Wechsler Adult Intelligence Scale (WAIS) Fourth Edition. Cardiorespiratory fitness was measured via heart rate recovery at minute 1 (HRR1) and 2 (HRR2), and exercise engagement (defined as percent of total exercise time spent in the prescribed heart rate zone). We measured pre and post changes using paired t-tests and mixed effects models, and investigated the association between cardiorespiratory and cognitive performance using multiple regression models. Cohen's d were calculated to estimate effect sizes.ResultsOverall, 63.4 % of participants demonstrated high engagement (≥ 70% total exercise time spent in the prescribed heart rate zone). There were significant pre-post improvements in verbal fluency and verbal memory, and a significant decrement in working memory, but these were associated with small effect sizes (Cohen's d <0.5). Concerning cardiorespiratory fitness, there was a pre-to-post significant improvement in HRR1 (p = 0.01, d = 0.30) and HRR2 (p < 0.001, d = 0.50). Multiple regressions revealed significant associations between cardiorespiratory and cognitive performance, but all were associated with small effect sizes (Cohen's d < 0.5). Interestingly, there were significant between-group differences in exercise engagement (all p < 0.001), with remote participants demonstrating greater exercise engagement than in-person participants.ConclusionImprovements in cognition and cardiorespiratory fitness were observed after 8 weeks of moderate to high-intensity exercise in aging adults. These results suggest that committing to a regular exercise regimen, even for a brief two-month period, can promote improvements in both cardiorespiratory fitness and cognitive performance, and that improvements are driven by exercise engagement

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10$^{−35}$ and <10$^{−8}$ respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10$^{−6}$). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10$^{−20}$) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Peer reviewe

The Neuroecology of Space Use: Investigating the Ecological Impacts and Neural Mechanisms of Spatial and Social Context

247 pagesA fundamental part of behavior is understanding how and why individual decisions are made. These decisions influence mating behavior, and can ultimately impact survival and reproductive success. An element oft overlooked is how the spatial environment provides an immutable backdrop and context for all such interactions. In this body of work, I explored how spatial and social contexts affect individual mating tactics, social dynamics, and underlying neural mechanisms in prairie voles (Microtus ochrogaster). First, I describe how sex-specific cognitive demands influence neural and behavioral phenotypes. I showed that males have better spatial performance and also decreased nonapeptide receptor expression in a crucial memory region of the brain. Next, I used an ecological model to demonstrate the dynamic nature of reproductive decision-making. I modeled the most advantageous times for males to seek extra pair copulations (EPC). I found that as EPC-seeking in the population increases, the optimal strategy shifts from monogamous to more promiscuous tactics. Then I provide evidence that intensity of intraspecific competition is an important factor shaping spatial memory. By manipulating intensity between contexts in semi-natural outdoor enclosures, I found that males demonstrate better spatial memory within male-biased contexts, indicating that spatial memory is particularly relevant for male-male interactions. Next, I asked how differential access to mates influences mixed paternity and overall reproductive success in female prairie voles living in semi-natural outdoor enclosures. When males outnumber females, females have fewer mating partners yet when females outnumber males they have multiple partners and high rates of mixed paternity. Lastly, I describe how socio-spatial learning ability impacts male mating tactics in outdoor enclosures. I tested whether cognitive ability is predictive of results from a chosen mating tactic. My data emphasize that individual mating tactics are uniquely influenced by context and cognitive abilities. Taken Together this research highlights the importance of understanding space use from multiple levels of investigation including brain, behavior, and semi-natural field studies. Through this integrative approach I developed a nuanced understanding of how space use impacts neural mechanisms, cognitive ability, and reproductive decisions.2022-06-0

Supplemental Material - A Pivotal Time and Place: University Place Attachment, Childhood Neighborhood Affordances, and Internalizing Symptoms in Emerging Adulthood

Supplemental Material for A Pivotal Time and Place: University Place Attachment, Childhood Neighborhood Affordances, and Internalizing Symptoms in Emerging Adulthood by Amber Tan, Marissa A. Rice, and Marlen Z. Gonzalez in Emerging Adulthood</p