Mitochondrial polymorphism shapes intrapopulation behavioural variation in wild
            Drosophila

Intrapopulation variation in behaviour, including activity, boldness and aggressiveness, is becoming more widely recognized and is hypothesized to substantially affect ecological and evolutionary dynamics. Although previous studies used candidate-gene approaches and genome-wide association analyses to identify genes correlated with variations in activity and aggressiveness, behavioural variation may not be fully captured in the nuclear genome, as it does not account for mitochondrial genomes. Mitochondrial genes encode products that are key regulators of the cellular energy-producing pathways in metabolic processes and are thought to play a significant role in life-history and reproductive traits. In this study, we considered many isofemale lines of Drosophila immigrans established from two wild populations to investigate whether intrapopulation variation in the mitochondrial genome affected activity level within this species. We identified two major haplogroups in these populations, and activity levels in both larvae and adults differed significantly between the two haplogroups. This result indicated that intrapopulation variation in activity level may be partially controlled by mitochondrial genes, along with the interaction between nuclear and mitochondrial genes and the age of individual organisms.

Download Full-text

The Contextual Essentiality of Mitochondrial Genes in Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.695351 ◽

2021 ◽

Vol 9 ◽

Author(s):

Luke W. Thomas ◽

Margaret Ashcroft

Keyword(s):

Cancer Cell ◽

Mitochondrial Gene ◽

Nuclear Genome ◽

Mitochondrial Genes ◽

Cancer Cell Proliferation ◽

Oxygen Species ◽

Eukaryotic Evolution ◽

Genome Wide ◽

Gene Level ◽

Microenvironmental Factors

Mitochondria are key organelles in eukaryotic evolution that perform crucial roles as metabolic and cellular signaling hubs. Mitochondrial function and dysfunction are associated with a range of diseases, including cancer. Mitochondria support cancer cell proliferation through biosynthetic reactions and their role in signaling, and can also promote tumorigenesis via processes such as the production of reactive oxygen species (ROS). The advent of (nuclear) genome-wide CRISPR-Cas9 deletion screens has provided gene-level resolution of the requirement of nuclear-encoded mitochondrial genes (NEMGs) for cancer cell viability (essentiality). More recently, it has become apparent that the essentiality of NEMGs is highly dependent on the cancer cell context. In particular, key tumor microenvironmental factors such as hypoxia, and changes in nutrient (e.g., glucose) availability, significantly influence the essentiality of NEMGs. In this mini-review we will discuss recent advances in our understanding of the contribution of NEMGs to cancer from CRISPR-Cas9 deletion screens, and discuss emerging concepts surrounding the context-dependent nature of mitochondrial gene essentiality.

Download Full-text

Massive bursts of transposable element activity in Drosophila

10.1101/010231 ◽

2014 ◽

Cited By ~ 1

Author(s):

Robert Kofler ◽

Viola Nolte ◽

Christian Schlötterer

Keyword(s):

Transposable Element ◽

Genome Evolution ◽

South African ◽

Evolutionary Dynamics ◽

Demographic History ◽

Rapid Evolution ◽

Activity Levels ◽

Genome Wide ◽

History Of ◽

Element Activity

The evolutionary dynamics of transposable element (TE) insertions have been of continued interest since TE activity has important implications for genome evolution and adaptation. Here, we infer the transposition dynamics of TEs by comparing their abundance in natural D. melanogaster and D. simulans populations. Sequencing pools of more than 550 South African flies to at least 320-fold coverage, we determined the genome wide TE insertion frequencies in both species. We show that 46 (49%) TE families in D. melanogaster and 44 (47%) in D. simulans experienced a recent burst of activity. The bursts of activity affected different TE families in the two species. While in D. melanogaster retrotransposons predominated, DNA transposons showed higher activity levels in D. simulans. We propose that the observed TE dynamics are the outcome of the demographic history of the two species, with habitat expansion triggering a period of rapid evolution.

Download Full-text

Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1513525113 ◽

2015 ◽

Vol 113 (6) ◽

pp. E754-E761 ◽

Cited By ~ 48

Author(s):

Lucia Pagani ◽

Patricia A. St. Clair ◽

Terri M. Teshiba ◽

Susan K. Service ◽

Scott C. Fears ◽

...

Keyword(s):

Bipolar Disorder ◽

Activity Rhythm ◽

Activity Level ◽

Activity Levels ◽

Genetic Linkage Analysis ◽

Systematic Analysis ◽

Genome Wide ◽

Significant Heritability ◽

Rhythm Activity ◽

Genetic Contributions

Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non–BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I–associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non–BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes.

Download Full-text

Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers

Genes ◽

10.3390/genes12050686 ◽

2021 ◽

Vol 12 (5) ◽

pp. 686

Author(s):

Alireza Nazarian ◽

Alexander M. Kulminski

Keyword(s):

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Significance Level ◽

Association Analyses ◽

Complex Disorders ◽

Specific Effects ◽

Genome Wide ◽

Genetic Mechanisms ◽

Sex Disparities ◽

Almost All

Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized and effective. We investigated sex-specific genetic associations with colorectal (CRCa) and lung (LCa) cancers using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent datasets. The genome-wide association analyses revealed that 33 SNPs were associated with CRCa/LCa at P < 5.0 × 10−6 neither males or females. Of these, 26 SNPs had sex-specific effects as their effect sizes were statistically different between the two sexes at a Bonferroni-adjusted significance level of 0.0015. None had proxy SNPs within their ±1 Mb regions and the closest genes to 32 SNPs were not previously associated with the corresponding cancers. The pathway enrichment analyses demonstrated the associations of 35 pathways with CRCa or LCa which were mostly implicated in immune system responses, cell cycle, and chromosome stability. The significant pathways were mostly enriched in either males or females. Our findings provided novel insights into the potential sex-specific genetic heterogeneity of CRCa and LCa at SNP and pathway levels.

Download Full-text

Later sleep timing predicts accelerated summer weight gain among elementary school children: a prospective observational study

International Journal of Behavioral Nutrition and Physical Activity ◽

10.1186/s12966-021-01165-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Jennette P. Moreno ◽

Javad Razjouyan ◽

Houston Lester ◽

Hafza Dadabhoy ◽

Mona Amirmazaheri ◽

...

Keyword(s):

Physical Activity ◽

Observational Study ◽

Sleep Duration ◽

Obesity Prevention ◽

Prospective Observational Study ◽

Light Exposure ◽

Activity Level ◽

Activity Levels ◽

School Year ◽

Children’S Sleep

Abstract Objectives and background Social demands of the school-year and summer environment may affect children’s sleep patterns and circadian rhythms during these periods. The current study examined differences in children’s sleep and circadian-related behaviors during the school-year and summer and explored the association between sleep and circadian parameters and change in body mass index (BMI) during these time periods. Methods This was a prospective observational study with 119 children ages 5 to 8 years with three sequential BMI assessments: early school-year (fall), late school-year (spring), and beginning of the following school-year in Houston, Texas, USA. Sleep midpoint, sleep duration, variability of sleep midpoint, physical activity, and light exposure were estimated using wrist-worn accelerometry during the school-year (fall) and summer. To examine the effect of sleep parameters, physical activity level, and light exposure on change in BMI, growth curve modeling was conducted controlling for age, race, sex, and chronotype. Results Children’s sleep midpoint shifted later by an average of 1.5 h during summer compared to the school-year. After controlling for covariates, later sleep midpoints predicted larger increases in BMI during summer, (γ = .0004, p = .03), but not during the school-year. Sleep duration, sleep midpoint variability, physical activity levels, and sedentary behavior were not associated with change in BMI during the school-year or summer. Females tended to increase their BMI at a faster rate during summer compared to males, γ = .06, p = .049. Greater amounts of outdoor light exposure (γ = −.01, p = .02) predicted smaller increases in school-year BMI. Conclusions Obesity prevention interventions may need to target different behaviors depending on whether children are in or out of school. Promotion of outdoor time during the school-year and earlier sleep times during the summer may be effective obesity prevention strategies during these respective times.

Download Full-text

Choroidal Thickness and Volume Modifications Induced by Aerobic Exercise in Healthy Young Adults

Ophthalmic Research ◽

10.1159/000511201 ◽

2020 ◽

Author(s):

Gema Insa-Sánchez ◽

Lorena Fuentes-Broto ◽

Alberto Cobos ◽

Elvira Orduna Hospital ◽

Francisco Segura ◽

...

Keyword(s):

Physical Activity ◽

Young Adults ◽

Physical Exercise ◽

Choroidal Thickness ◽

Activity Level ◽

Enhanced Depth Imaging ◽

Activity Levels ◽

Imaging Protocol ◽

Post Exercise ◽

Physical Activity Levels

Introduction: Our aim was to evaluate the changes in choroidal thickness (CT) and volume (CV) following aerobic physical exercise in healthy young adults. Methods: This study included 72 eyes from healthy volunteers between 22 and 37 years old. Using the International Physical Activity Questionnaire, total physical activity was computed. Measurements using an autorefractometer, ocular biometry, and spectral-domain optical coherence tomography using the Enhanced Depth Imaging protocol were taken. OCT was performed as a baseline measurement and after performing 10 min of dynamic physical exercise (3 and 10 min post-exercise). The choroidal layer was manually segmented, and the CT and CV in different areas from the Early Treatment Diabetic Retinopathy Study grid were obtained. Results: In healthy adults, at 3 min post-exercise, CT was higher in the subfoveal, the 3-mm nasal, and the 6-mm superior areas. Between 3 and 10 min post-exercise, the CT was reduced in all areas, and in some areas, the values were even smaller than the baseline measurements. The CV values showed changes after exercise similar to those of thickness. The total CV recovery after exercise was related to sex and physical activity level. Conclusion: Individuals with higher physical activity habits had greater CV at rest than those with lower physical activity levels. During exercise, healthy young people adjust CT and CV. At 3 min post-exercise, CT and CV increase. Women and individuals with greater physical activity levels reduce their total CV more than others during recovery.

Download Full-text

Nuclear genome-wide associations with mitochondrial heteroplasmy

Science Advances ◽

10.1126/sciadv.abe7520 ◽

2021 ◽

Vol 7 (12) ◽

pp. eabe7520

Author(s):

Priyanka Nandakumar ◽

Chao Tian ◽

Jared O’Connell ◽

David Hinds ◽

Andrew D. Paterson ◽

...

Keyword(s):

Nuclear Genome ◽

Multiple Roles ◽

European Ancestry ◽

Mitochondrial Transcription Factor ◽

Genome Wide ◽

Mtdna Sequence ◽

Nuclear Component ◽

Mitochondrial Transcription Factor A ◽

Mitochondrial Heteroplasmy ◽

The Stability

The role of the nuclear genome in maintaining the stability of the mitochondrial genome (mtDNA) is incompletely known. mtDNA sequence variants can exist in a state of heteroplasmy, which denotes the coexistence of organellar genomes with different sequences. Heteroplasmic variants that impair mitochondrial capacity cause disease, and the state of heteroplasmy itself is deleterious. However, mitochondrial heteroplasmy may provide an intermediate state in the emergence of novel mitochondrial haplogroups. We used genome-wide genotyping data from 982,072 European ancestry individuals to evaluate variation in mitochondrial heteroplasmy and to identify the regions of the nuclear genome that affect it. Age, sex, and mitochondrial haplogroup were associated with the extent of heteroplasmy. GWAS identified 20 loci for heteroplasmy that exceeded genome-wide significance. This included a region overlapping mitochondrial transcription factor A (TFAM), which has multiple roles in mtDNA packaging, replication, and transcription. These results show that mitochondrial heteroplasmy has a heritable nuclear component.

Download Full-text

82 The impact of feeding treats containing cannabidiol (CBD) on the daily activity level of dogs

Journal of Animal Science ◽

10.1093/jas/skaa278.109 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 60-61

Author(s):

Elizabeth M Morris ◽

Susanna E Kitts-Morgan ◽

Dawn M Spangler ◽

Kyle R McLeod ◽

David L Harmon

Keyword(s):

Daily Activity ◽

Block Design ◽

Companion Animals ◽

Total Activity ◽

Time Of Day ◽

Activity Level ◽

Activity Levels ◽

Quiet Time ◽

Activity Duration ◽

The Impact

Abstract Growing public interest in and use of Cannabidiol (CBD) in companion animals has amplified the need to elucidate potential impacts. The purpose of this investigation was to determine the impact of CBD on daily activity of adult dogs. Twenty-four dogs (18.0 ± 3.4 kg) were utilized in a randomized complete block design with treatments consisting of control, 2 mg CBD/kg BW/d, and 4 mg CBD/kg BW/d split between two treats administered after twice-daily exercise (7:00-9:00 and 17:00-19:00). Four hours each day (10:00-12:00, AM and 13:30-15:30, PM), were designated as time when no persons entered the kennels, with 2 h designated as Quiet Time and the other 2 h as Music Time, where calming music played over speakers. Quiet and Music sessions were randomly allotted to daily AM or PM times. Activity monitors were fitted to dogs’ collars for continuous collection of activity parameters. Data were collected over a 2-wk baseline period to block dogs by activity level (high or low) before randomly assigning dogs within each block to treatments. After 1 wk of treatment adaptation, activity parameters were collected for 2 wk. Data were tested for normality using the UNIVARIATE procedure in SAS before examining differences using the MIXED procedure in SAS, including effects of treatment, day, session (Quiet or Music), time of day (AM or PM), and accompanying interactions. CBD did not alter total activity points (P = 0.9971) or activity duration (P = 0.8776). CBD tended (P = 0.0692) to reduce scratching compared to control. Irrespective of treatment, dogs were more active in PM than AM (P < 0.0001). Regardless of session, dogs receiving 4 mg/kg/d tended (P = 0.0914) to be less active in the PM than control. CBD did not affect activity duration during exercise periods (P = 0.1425), but dogs receiving CBD ran more than control (P = 0.0339). These results indicate that when supplemented up to 4 mg/kg/d, CBD does not negatively impact daily activity levels of dogs.

Download Full-text

Reduced level of physical activity during COVID-19 pandemic is associated with depression and anxiety levels: an internet-based survey

BMC Public Health ◽

10.1186/s12889-021-10470-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Paulo José Puccinelli ◽

Taline Santos da Costa ◽

Aldo Seffrin ◽

Claudio Andre Barbosa de Lira ◽

Rodrigo Luiz Vancini ◽

...

Keyword(s):

Physical Activity ◽

Mood Disorders ◽

Physical Activity Level ◽

Negative Impact ◽

Mood State ◽

Activity Level ◽

Activity Levels ◽

Depression And Anxiety ◽

Social Distancing ◽

Physical Activity Levels

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in a strong negative impact on economic and social life worldwide. It has also negatively influenced people’s general health and quality of life. The aim of the present study was to study the impact of social distancing on physical activity level, and the association between mood state (depression and anxiety level) or sex with actual physical activity levels, the change in physical activity caused by social distancing period, the adhesion level to social distancing, the adoption time of social distancing, family income and age. Methods A self-administered questionnaire with personal, quarantine, physical activity, and mood state disorders information’s was answered by 2140 Brazilians of both sex who were recruited through online advertising. Results The physical activity level adopted during the period of social distancing (3.5 ± 0.8) was lower than that the adopted prior to the pandemic period (2.9 ± 1.1, p < 0.001). Thirty percent of the participants presented symptoms of moderate/severe depression and 23.3% displayed moderate/severe anxiety symptoms. A greater presence of symptoms related to anxiety and depression were associated with low physical activity levels, low family monthly income, and younger age. A higher percentage of men who had no mood disorders was observed among those who were very active than among those less active. Conclusion The COVID-19 pandemic has a negative impact on physical activity. Those who reduced their level of physical activity had the highest levels of mood disorders. Therefore, physical activity programs should be encouraged, while respecting the necessary social distancing to prevent the spread of Severe Acute Respiratory Syndrome Coronavirus 2.

Download Full-text

Quantitative Trait Loci for the Monoamine-Related Traits Heart Rate and Headless Behavior inDrosophila melanogaster

Genetics ◽

10.1093/genetics/157.1.283 ◽

2001 ◽

Vol 157 (1) ◽

pp. 283-294 ◽

Cited By ~ 2

Author(s):

Kristie Ashton ◽

Ana Patricia Wagoner ◽

Roland Carrillo ◽

Greg Gibson

Keyword(s):

Heart Rate ◽

Genetic Variation ◽

Recombinant Inbred Lines ◽

Model Organism ◽

Interval Mapping ◽

Activity Levels ◽

Environmental Variance ◽

Genome Wide ◽

A Genome ◽

Monoamine Receptors

AbstractDrosophila melanogaster appears to be well suited as a model organism for quantitative pharmacogenetic analysis. A genome-wide deficiency screen for haploinsufficient effects on prepupal heart rate identified nine regions of the genome that significantly reduce (five deficiencies) or increase (four deficiencies) heart rate across a range of genetic backgrounds. Candidate genes include several neurotransmitter receptor loci, particularly monoamine receptors, consistent with results of prior pharmacological manipulations of heart rate, as well as genes associated with paralytic phenotypes. Significant genetic variation is also shown to exist for a suite of four autonomic behaviors that are exhibited spontaneously upon decapitation, namely, grooming, grasping, righting, and quivering. Overall activity levels are increased by application of particular concentrations of the drugs octopamine and nicotine, but due to high environmental variance both within and among replicate vials, the significance of genetic variation among wild-type lines for response to the drugs is difficult to establish. An interval mapping design was also used to map two or three QTL for each behavioral trait in a set of recombinant inbred lines derived from the laboratory stocks Oregon-R and 2b.

Download Full-text