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PubMed2026

Obesity Polygenic Risk and Healthy Lifestyle Interactions on Weight Trajectories in Women and Men.

BACKGROUND: Genetics and environmental factors contribute to obesity risk, but the extent to which healthy behaviors can offset genetic susceptibility remains unclear. We examined the interaction between obesity polygenic risk and a composite healthy lifestyle score on body mass index (BMI) trajectories in women and men. METHODS: We analyzed 13 780 women from the Nurses' Health Study and 8242 men from the Health Professionals Follow-Up Study, all of European ancestry and free of major chronic disease at baseline. The lifestyle score comprised American Heart Association Essential 8 components (nonsmoking, physical activity, healthy eating, adequate sleep) plus moderate alcohol intake, modeled as a time-varying variable. A genome-wide polygenic score for BMI was derived from genome-wide association study. Adjusted linear mixed-effects models estimated associations and interactions on biennial BMI measures over up to 26 years. RESULTS: Each SD increase in the polygenic score was associated with 1.80 kg/m2 (95% CI, 1.72-1.87) and 1.12 kg/m2 (95% CI, 1.06-1.19) higher BMI in women and men, respectively. Significant interactions between the polygenic score and healthy lifestyle score (both P<0.05) showed a dose-response attenuation of the genetic effects with healthier lifestyles. Comparing the healthiest with the least healthy lifestyle groups, genetic effects on BMI were 35% lower in women and 28% lower in men. In sensitivity analyses, higher diet quality and physical activity consistently attenuated genetic associations in both cohorts, whereas current smoking showed similar effects in women only. CONCLUSIONS: Adherence to a healthier lifestyle attenuated the association between obesity polygenic risk and BMI in a dose-response manner.

Humans↗

PubMed2025

Genome sequencing and population genomics provide insights into the demographic history, genetic load, and local adaptation of an endangered Tertiary relict.

Endangered Tertiary relict trees represent an exceptional evolutionary heritage with small and isolated populations, yet little is known about how demographic history, local adaptation, and genetic load have affected their long-term survival and extinction risk. We performed whole-genome sequencing and population genomic analyses on Ulmus elongata L. K. Fu & C. S. Ding, an endangered Tertiary relict tree endemic to East Asia. By integrating genomes from U. elongata and seven other endangered trees from public databases, we identified rate-decelerated genes across endangered trees and genes under positive selection of U. elongata associated with tissue development, detoxification, and immune response, and signal transduction and regulation mechanisms potentially leading to endangered status. Demographic analyses revealed continuous population decline from the late Miocene to present, especially during the last glacial maximum (LGM) and last 10 000 years. Spearman correlation indicated a strong negative relationship between effective population size and human population density (rpopulation density = -0.90, P < 0.001) as well as cropland use (rcropland use = -0.89, P < 0.001). Genotype-environment association (GEA) analyses identified a set of candidate genes associated with temperature and precipitation, supporting a polygenic adaptation model in U. elongata. Overall, our findings underscore the severe population bottlenecks that have led to the fixation of strongly deleterious mutations and inbreeding, further compromising the adaptive potential and long-term viability of U. elongata. Furthermore, assessments of genomic vulnerability under future climate scenarios revealed higher genetic offsets in northern region of Fujian and Jiangxi populations, suggesting these regions require prioritized conservation efforts due to reduced adaptive capacity.

Endangered Species↗

PubMed1988

Angular homeostasis II: Pursuit of a moving target in a plane and some implications for cardiac teratology.

A model of cardiac ontogenesis is analyzed. It is cast in terms of the geometry of the pursuit of a linearly moving target by the growth of a chain of cells in the same plane, the pursuer, which at each step adjusts its direction of growth towards the current position of the target. The endpoint is the fusion between them, which can occur in 2 modes: either by the leading cell of the pursuer catching up with the target (pursuer-mediated fusion, or PMF) or by the target running into the preformed side of the pursuer (target-mediated fusion, or TMF). The causal specifications are the step size, the speed of the pursuer, the speed of the target, the restoration constant, and the initial direction of the pursuer; the outcome variables are the number of steps to fusion and the mode of fusion. The pattern of behavior is complicated, being more-or-less regular over large tracts of values, interspersed with abrupt, threshold-like changes that may generate a dichotomous pattern of inheritance despite a continuous gradation of genetic or other causes. The temporary abolition of the correction process (a change introduced to simulate the pattern of the effect of a teratogen) may delay fusion and suggest how a septum may fail to fuse, the ductus arteriosus to close, or an endocardial cushion to form. But the model also predicts that under certain plausible conditions, the "teratogen" would speed up fusion and hence perhaps offset a genetic predisposition to a congenital defect.

Heart Defects, Congenital↗

PubMed2025

Common gardens reveal genomic susceptibility and vulnerability to climate change in Eucalyptus.

Accelerated global climate change and increased species introduction across international scales have raised concerns about the potential for trees to experience maladaptation or lagging adaptation in response to these environmental shifts. However, our knowledge regarding the relationship between the genomic metrics used to predict maladaptation and actual fitness proxies in trees remains limited. Here, we present a population genomic analysis of 295 families from 28 provenances of Eucalyptus pellita, a widely cultivated fast-growing tree species, and conducted two common garden experiments. Genomic susceptibility encompassing individual heterozygosity (H), genomic inbreeding (FROH), and genomic load (inferred from deleterious mutations) exhibited distinct geographic patterns, shedding light on the origin and evolutionary history of E. pellita. The genetic basis of local adaptation was elucidated through genotype-environment associations and genome-wide association studies, including 198 loci associated with climate and 2388 loci regulating different traits. Furthermore, Australian provenances have higher genomic vulnerability under prospective climate alterations than Papua New Guinea and Indonesia provenances. By integrating phenotypic data across two common gardens, the relationship between leaf functional traits and predicted metrics of maladaptation was closer than growth attributes. Notably, pronounced natural selection signals linked to leaf morphogenesis have been identified by comparing two lineages spanning the oceans. This study underscores the immense potential of leveraging genomic susceptibility and genomic vulnerability to decipher the local (mal)adaptation of forest trees.

Eucalyptus↗

PubMed2026

Landscape Genomics Reveals Divergent Adaptation Modes and Predicts Climate Vulnerability in Xinjiang Indigenous Sheep.

Climate change increasingly endangers precious indigenous sheep germplasm resources distributed across diverse Chinese landscapes, and systematically decoding their polygenic climate-adaptive genetic mechanisms is essential for targeted breed conservation and long-term sustainable pastoral production. Whole-genome resequencing data from 93 individuals covering six representative local sheep breeds were analyzed in this work. After filtering highly collinear climate variables, three mature landscape genomic approaches were jointly applied to identify environment-linked gene variants, while two predictive metrics across ten CMIP6 future climate scenarios quantified each breed's long-term adaptive risks. Six temperature- and water-related environmental factors jointly drove sheep population genetic differentiation, with temperature fluctuation indices showing markedly stronger explanatory power. Detected adaptive genes were significantly enriched in ion transport, energy metabolism and cellular stress response pathways. Future projections indicated western breeds (Bayinbuluke, Cele Black, Xiahe) face severe maladaptation risks under high-emission SSP370 scenarios by 2100, whereas central and eastern breeds possess much broader climate tolerance. This study systematically reveals the core genomic basis of ovine climate adaptation and quantifies distinct breed-specific climate vulnerability, providing solid reliable theoretical support for precision germplasm conservation and selective breeding of climate-resilient sheep varieties.

adaptive loci↗

PubMed1975

Effects of various medical and social pracitices on the frequency of genetic disorders.

The effects of a number of new medical and social practices on the incidence of genetic diseases and gene frequency have been studied. The results deal with short-term effects, since these are of most practical importance, and with the combined effects of several factors acting together. The size of any effects depends on the feasibility of the different practices and on the extent to which they are adopted by the population. Most of the practices reduce the incidence of the diseases in the next generation, but some may be dysgenic. For example, improved treatment of affected individuals in dominant and X-linked diseases could lead to improved reproductive fitness, higher gene frequencies, and to an increased incidence in future generations. However, such deleterious effects may be avoided by genetic counseling or offset by other preventive practices. In recessive disorders, a small reduction in the average fitness of carfiers detected by population screening would outweigh any deleterious effects of other practices. In general there seems to be little cause for alarm about the deleteious effects of the new medical and social practices being adopted.

Abortion, Spontaneous↗

PubMed1991

Strain differences in the pattern and intensity of wheel running activity in laboratory rats.

Wheel running activity rhythms of three inbred rat strains, ACI/Ztm, BH/Ztm, and LEW/Ztm, were compared in order to evaluate the effect of genetic differences on circadian rhythm parameters. Significant strain differences were found in the general pattern of the activity rhythms and their characteristic periodicities as well as in the amount and duration of wheel running activity and the timing of activity onsets and offsets. The results suggest that genetic differences exist in the coupling of the multiple circadian oscillators that generate the overall pattern of wheel running activity.

Activity Cycles↗

PubMed1985

Neural plasticity in schizophrenia.

No current biological hypothesis can assimilate the genetic, environmental, and clinical features of schizophrenia. If, as some authors contend, environmental factors have important effects on the course of schizophrenia, then a fruitful research concern may be the adaptation of neuronal circuitry to environmental changes. The plasticity of neuronal connections has been studied by subjecting animals to neurosurgical lesions, brain electro-stimulation, and a variety of rearing environments. The present article approaches the schizophrenia research literature from a theoretical perspective which takes into account the plasticity of neuronal connections. In a speculative manner, it demonstrates how neural plasticity concepts can be invoked to explain the following seemingly disparate features of schizophrenia: the pharmacological support for the dopamine hypothesis, the delayed onset and offset of neuroleptic antipsychotic action, genetic and environmental influences in schizophrenia, the regional alterations in brain structure and function seen in chronic schizophrenic patients, and the various types of behavioral symptoms exhibited by schizophrenic patients. In view of the explanatory potential of neural plasticity concepts, a research program that focuses on these concepts seems warranted.

Animals↗

PubMed2025

Conservation genomics of a threatened subtropical Rhododendron species highlights the distinct conservation actions required in marginal and admixed populations.

With the impact of climate change and anthropogenic activities, the underlying threats facing populations with different evolutionary histories and distributions, and the associated conservation strategies necessary to ensure their survival, may vary within a species. This is particularly true for marginal populations and/or those showing admixture. Here, we re-sequence genomes of 102 individuals from 21 locations for Rhododendron vialii, a threatened species distributed in the subtropical forests of southwestern China that has suffered from habitat fragmentation due to deforestation. Population structure results revealed that R. vialii can be divided into five genetic lineages using neutral single-nucleotide polymorphisms (SNPs), whereas selected SNPs divide the species into six lineages. This is due to the Guigu (GG) population, which is identified as admixed using neutral SNPs, but is assigned to a distinct genetic cluster using non-neutral loci. R. vialii has experienced multiple genetic bottlenecks, and different demographic histories have been suggested among populations. Ecological niche modeling combined with genomic offset analysis suggests that the marginal population (Northeast, NE) harboring the highest genetic diversity is likely to have the highest risk of maladaptation in the future. The marginal population therefore needs urgent ex situ conservation in areas where the influence of future climate change is predicted to be well buffered. Alternatively, the GG population may have the potential for local adaptation, and will need in situ conservation. The Puer population, which carries the heaviest genetic load, needs genetic rescue. Our findings highlight how population genomics, genomic offset analysis, and ecological niche modeling can be integrated to inform targeted conservation.

Rhododendron↗

PubMed1991

Use of an animal model in situations of limited subclass numbers and high degrees of relationships.

Breeding value estimation procedures for two traits with moderate and high heritability were evaluated by using a single-trait animal model and computer-simulated data designs. Of interest were the effects of differing numbers of animals and degrees of relationships among animals within and across contemporary groups (tests). Test effects were assumed fixed and animal effects were assumed random. Family size, number of families per contemporary group, and degree of genetic relationships within and across contemporary groups were varied to determine interrelationships among the factors. Results were compared on the basis of accuracy by using both the correlation of true and estimated breeding values and the prediction error variance obtained from the inverse of the coefficient matrix of the mixed-model equations. Small contemporary groups in conjunction with evaluation of closely related families caused average accuracy to decrease relative to that obtained with the same number of unrelated animals because genetically related animals were less accurately evaluated relative to one another. Connecting contemporary groups with a genetic relationship matrix formed a large set of interdependent equations and improved the average accuracy of predicted breeding values. The slight decrease in accuracy for genetically related animals was more than offset by the increase in accuracy of evaluation for their unrelated test mates because the proportion of fixed effects to random effects was smaller. Care must be exercised in designing evaluation schemes involving small populations, and the decision of which fixed effects to include in the model is critical.

Animals↗

PubMed2026

Genomic-Environmental Integration Predicts Climate Vulnerability and Adaptive Potential of Tibetan Plateau Herpetofauna.

The herpetofauna of the Tibetan Plateau, home to Earth's highest-elevation ectothermic vertebrates, face escalating threats from rapid climate change. However, conventional conservation strategies often overlook intraspecific genetic variation and adaptive potential, limiting their predictive accuracy and effectiveness. Here, we integrate whole-genome resequencing data with environmental modeling to assess climate vulnerability in two endemic species: Nanorana parkeri (Tibetan frog) and Thermophis baileyi (hot-spring snake). Results suggest that the western populations of the two species exhibit higher genomic offsets under future climate, while some eastern populations of the Tibetan frog face a decrease in niche suitability, and the hot-spring snake will experience varying degrees of loss of suitable habitats. Furthermore, heterozygosity, genetic diversity, and genetic load demonstrate significant correlations with genomic offsets, suggesting that low genetic diversity and high genetic load may weaken the potential to adapt to environmental changes. Based on a genome-niche index that combines genomic offsets with niche suitability change, we identified evolutionary rescue populations that are potentially tolerant to climate change. Our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive potential and enable effective conservation management of high-altitude herpetofauna under rapid climate change.

Animals↗

PubMed1992

Selection for postweaning growth in inbred Hereford cattle: the Fort Keogh, Montana line 1 example.

Demographic characteristics and genetic trends in birth weight and pre- and postweaning ADG were examined in a population of Hereford cattle (Line 1). Line 1 was founded largely from two paternal half-sib sires and has been selected for postweaning growth. There were pedigree records on 951 members of the base population that predated 1935, when data collection began. Numbers of records analyzed using mixed-model methodology were 4,716 birth weight, 4,427 preweaning ADG, and 3,579 postweaning ADG. Birth weight and preweaning ADG were considered to have direct and maternal genetic components. Inbreeding accumulated rapidly from 1935 to 1960 and more slowly (.22%/yr) thereafter. Any reduction in additive genetic variance due to inbreeding and selection may have been offset by a concurrent reduction in generation interval that was observed as time progressed. Expected selection differential for 365-d weight, averaged over sexes, was 31.2 kg per generation. For birth weight, annual genetic trends in direct and maternal effects were 42 +/- 3 g and 15 +/- 3 g, respectively. Annual direct and maternal genetic trends for preweaning ADG were .70 +/- .06 g/d and .63 +/- .06 g/d, respectively. Direct response in postweaning ADG was linear and equal to 5.3 +/- .6 g.d-1.yr-1. As a result, estimated breeding values of birth weight, 200-d weight, and 365-d weight increased by 3.2 kg, 14.5 kg, and 62.4 kg, respectively, from 1935 to 1989. Selection within Line 1 was effective in increasing genetic potential for growth over 13 generations. No selection plateau was observed in any of the traits examined.

Age Factors↗

PubMed1992

Genetic disease: effects on human health.

Genetic variation (chromosomal, single gene, multifactorial) is a significant cause of morbidity and mortality in human populations. It increases in relative importance along with improvement in socioeconomic and environmental conditions and in association with prudent lifestyle. It affects longevity, development, reproductive capability, schooling, work and appearance of individuals. Its evidence is ubiquitous in the health care disciplines. Health care systems in general do not provide resources to meet the demand for genetics. Prevention of mutations, avoidance of their effects by reproductive counseling and treatment to offset mutant phenotypes are increasingly relevant scientific initiatives with broad social implications.

Adolescent↗

PubMed1986

Decreased effectiveness of GABA-mediated inhibition in the inferior colliculus of the genetically epilepsy-prone rat.

The inferior colliculus (IC) is a critical site for induction of audiogenic seizures in the genetically epilepsy-prone rat (GEPR). Abnormal response properties observed in inferior colliculus neurons of that strain include a high incidence of onset-offset responses which may be a form of afterdischarge. These response abnormalities may involve altered actions of neurotransmitters in that region of the brain. GABA is implicated as a transmitter in endogenous sound-induced inhibition in the inferior colliculus. Endogenous inhibition and the actions of agents that affect GABA receptors were examined in inferior colliculus neurons in epileptic and normal rats. The iontophoretic dose (current) of GABA required to suppress neuronal firing in the epilepsy-prone rat was significantly greater than that required in neurons of the normal rat. A form of endogenous (binaural) inhibition in inferior colliculus neurons, which is proposed to be GABA-mediated, was also significantly reduced in the epilepsy-prone rat as compared with the normal rat. A benzodiazepine (flurazepam) which enhances the action of GABA in many brain sites including the inferior colliculus was significantly less effective than normal when applied iontophoretically onto the same neurons of the epilepsy-prone rat. The GABAA antagonist, bicuculline, which blocks the effect of GABA on inferior colliculus neurons, frequently induced the onset-offset response in neurons not previously exhibiting this pattern. These findings suggest that the reduction of GABA-mediated inhibition in the genetically epilepsy-prone rat may result in the increased incidence of afterdischarges in neurons of the inferior colliculus and may serve as an important mechanism of epileptogenesis in audiogenic seizures in this genetic form of epilepsy.

Animals↗

PubMed2024

Interspecific transfer of genetic information through polyploid bridges.

Hybridization blurs species boundaries and leads to intertwined lineages resulting in reticulate evolution. Polyploidy, the outcome of whole genome duplication (WGD), has more recently been implicated in promoting and facilitating hybridization between polyploid species, potentially leading to adaptive introgression. However, because polyploid lineages are usually ephemeral states in the evolutionary history of life it is unclear whether WGD-potentiated hybridization has any appreciable effect on their diploid counterparts. Here, we develop a model of cytotype dynamics within mixed-ploidy populations to demonstrate that polyploidy can in fact serve as a bridge for gene flow between diploid lineages, where introgression is fully or partially hampered by the species barrier. Polyploid bridges emerge in the presence of triploid organisms, which despite critically low levels of fitness, can still allow the transfer of alleles between diploid states of independently evolving mixed-ploidy species. Notably, while marked genetic divergence prevents polyploid-mediated interspecific gene flow, we show that increased recombination rates can offset these evolutionary constraints, allowing a more efficient sorting of alleles at higher-ploidy levels before introgression into diploid gene pools. Additionally, we derive an analytical approximation for the rate of gene flow at the tetraploid level necessary to supersede introgression between diploids with nonzero introgression rates, which is especially relevant for plant species complexes, where interspecific gene flow is ubiquitous. Altogether, our results illustrate the potential impact of polyploid bridges on the (re)distribution of genetic material across ecological communities during evolution, representing a potential force behind reticulation.

Polyploidy↗

PubMed1988

Genetically determined differences in ethanol sensitivity influenced by body temperature during intoxication.

The present study investigated the importance of body temperature during intoxication in mediating differences between five inbred strains of mice (C57BL/6J; BALB/cJ; DBA/2J; A/HeJ; 129/J) in their acute sensitivity to the hypnotic effects of ethanol. Mice exposed to 22 degrees C after ethanol injection became hypothermic and exhibited statistically significant differences between strains in rectal temperatures at the return of the righting reflex (RORR), duration of loss of the righting reflex (LORR), and blood and brain ethanol concentrations at RORR. Exposure to 34 degrees C after injection offset ethanol-hypothermia and markedly reduced strain-related differences in rectal temperatures and blood and brain ethanol concentrations at RORR. Brain ethanol concentrations at RORR were significantly lower in C57, BALB, DBA and A/He mice exposed to 34 degrees C compared to mice exposed to 22 degrees C during intoxication suggesting that offsetting hypothermia increased ethanol sensitivity in these strains. Taken with previous in vitro studies, these results suggest that genetically determined differences in acute sensitivity to the behavioral effects of ethanol reflect differences in body temperature during intoxication as well as differences in sensitivity to the initial actions of ethanol at the cellular level.

Acclimatization↗

PubMed2026

Climate-Driven Niche Tracking and Genomic Resilience Shape Future Distribution of a Widespread Agricultural Weed.

Understanding how agriculturally important species respond to environmental change is critical for maintaining productivity, mitigating agroecosystem threats and sustaining resilience. While crops have traditionally been the focus in agroecosystems, agricultural weeds are integral components that often face even stronger selective pressures, making them powerful models for investigating ecological and evolutionary responses to climatic and human-mediated challenges. Insights from how weeds adapt rapidly under these pressures can inform strategies to improve agricultural outcomes, since both pests and crops evolve under the same multivariate selective pressures. Here, we integrate two centuries of distribution records with whole-genome sequencing from natural populations of the most damaging weed in Europe-Alopecurus myosuroides (blackgrass) - to examine its ecological and evolutionary responses in agroecosystems. Blackgrass largely maintained its historical climatic niche, expanding its range primarily by tracking environments analogous to those it historically occupied. Genome-wide analyses revealed a polygenic basis of environmental responses, with most loci linked to single environmental variables and a subset showing limited environmental pleiotropy, indicating modular adaptation to the complex selective pressures of managed agricultural landscapes. Coupling these genomic-environment relationships with projected climate change and genomic offset analyses indicated that most blackgrass populations will remain well aligned with future conditions. Our findings show that ecological niche tracking and polygenic adaptation allow agricultural weeds like blackgrass to persist under rapid environmental change, offering insights relevant not only for weed management but also for designing resilient cropping systems under future climates.

Plant Weeds↗

PubMed2025

Dosage sensitivity of the loop extrusion rate confers tunability to genome folding while creating vulnerability to genetic disruption.

Genome folding is not static, but emerges from dynamic processes that control transcription, replication, recombination, and repair. DNA loop extrusion by cohesin is central to genome organization, yet it remains unclear how cells can tune extrusion kinetics to achieve precise and functional chromosome folding patterns. Here we discover extrusion rate acts as a tunable biophysical parameter in cells, quantitatively dialed by the respective dosage of the cohesin cofactors NIPBL and PDS5. Modulation of extrusion rate can offset changes in cohesin lifetime to buffer steady-state chromosome structure and transcriptional states, even in the face of abnormal extrusion dynamics. These findings provide a long-sought mechanistic basis for the genetic interactions between cohesin cofactors and the molecular origin of haploinsufficiency in cohesinopathies, such as Cornelia de Lange syndrome.

Journal Article↗