Transmission Bias Research Articles

B chromosomes reveal a female meiotic drive suppression system in Drosophila melanogaster

Selfish genetic elements use a myriad of mechanisms to drive their inheritance and ensure their survival into the next generation, often at a fitness cost to its host.1,2 Although the catalog of selfish genetic elements is rapidly growing, our understanding of host drive suppression systems that counteract self-seeking behavior is lacking. Here, we demonstrate that the biased transmission of the non-essential, non-driving B chromosomes in Drosophila melanogaster can be achieved in a specific genetic background. Combining a null mutant of matrimony, a gene that encodes a female-specific meiotic regulator of Polo kinase,3,4 with the TM3 balancer chromosome creates a driving genotype that is permissive for the biased transmission of the B chromosomes. This drive is female-specific, and both genetic components are necessary, but not individually sufficient, for permitting a strong drive of the B chromosomes. Examination of metaphase I oocytes reveals that B chromosome localization within the DNA mass is mostly abnormal when drive is the strongest, indicating a failure of the mechanism(s) responsible for the proper distribution of B chromosomes. We propose that some proteins important for proper chromosome segregation during meiosis, like Matrimony, may have an essential role as part of a meiotic drive suppression system that modulates chromosome segregation to prevent genetic elements from exploiting the inherent asymmetry of female meiosis.

Sentiment analysis of the Twitter response to Netflix's Our Planet documentary.

The role of nature documentaries in shaping public attitudes and behavior toward conservation and wildlife issues is unclear. We analyzed the emotional content of over 2 million tweets related to Our Planet, a major nature documentary released on Netflix, with dictionary and rule-based automatic sentiment analysis. We also compared the sentiment associated with species mentioned in Our Planet and a set of control species with similar features but not mentioned in the documentary. Tweets were largely negative in sentiment at the time of release of the series. This effect was primarily linked to the highly skewed distributions of retweets and, in particular, to a single negatively valenced and massively retweeted tweet (>150,000 retweets). Species mentioned in Our Planet were associated with more negative sentiment than the control species, and this effect coincided with a short period following the airing of the series. Our results are consistent with a general negativity bias in cultural transmission and document the difficulty of evoking positive sentiment, on social media and elsewhere, in response to environmental problems.

Parent-offspring genotyped trios unravelling genomic regions with gametic and genotypic epistatic transmission bias on the cattle genome.

Several biological mechanisms affecting the sperm and ova fertility and viability at developmental stages of the reproductive cycle resulted in observable transmission ratio distortion (i.e., deviation from Mendelian expectations). Gene-by-gene interactions (or epistasis) could also potentially cause specific transmission ratio distortion patterns at different loci as unfavorable allelic combinations are under-represented, exhibiting deviation from Mendelian proportions. Here, we aimed to detect pairs of loci with epistatic transmission ratio distortion using 283,817 parent-offspring genotyped trios (sire-dam-offspring) of Holstein cattle. Allelic and genotypic parameterization for epistatic transmission ratio distortion were developed and implemented to scan the whole genome. Different epistatic transmission ratio distortion patterns were observed. Using genotypic models, 7, 19 and 6 pairs of genomic regions were found with decisive evidence with additive-by-additive, additive-by-dominance/dominance-by-additive and dominance-by-dominance effects, respectively. Using the allelic transmission ratio distortion model, more insight was gained in understanding the penetrance of single-locus distortions, revealing 17 pairs of SNPs. Scanning for the depletion of individuals carrying pairs of homozygous genotypes for unlinked loci, revealed 56 pairs of SNPs with recessive epistatic transmission ratio distortion patterns. The maximum number of expected homozygous offspring, with none of them observed, was 23. Finally, in this study, we identified candidate genomic regions harboring epistatic interactions with potential biological implications in economically important traits, such as reproduction.

Visibility Bias in the Transmission of Consumption Beliefs and Undersaving

ABSTRACTWe model visibility bias in the social transmission of consumption behavior. When consumption is more salient than nonconsumption, people perceive that others are consuming heavily, and infer that future prospects are favorable. This increases aggregate consumption in a positive feedback loop. A distinctive implication is that disclosure policy interventions can ameliorate undersaving. In contrast with wealth‐signaling models, information asymmetry about wealthreducesoverconsumption. The model predicts that saving is influenced by social connectedness, observation biases, and demographic structure, and provides new insight into savings rates. These predictions are distinct from other common models of consumption distortions.

Gamma-Aminobutyric Acid Type A Receptor Variants are Associated with Autism Spectrum Disorders.

Despite several efforts to identify the causes of autism spectrum disorders (ASD), its etiology remains still unclear. Among other aspects, genes that encode neurotransmitter receptors are strong candidates for autism. Here, we wanted to study some genetic variants of gamma-aminobutyric acid (GABA) receptor subunit genes GABRB3, GABRG3, and GABRA5, located on chromosome 15q11-q13 that might contribute to the etiology of ASD in the affected children of West Bengal. rs7180158, rs2081648 (GABRB3); rs12910555 (GABRG3); rs35399885, rs35832850 (GABRA5) were analyzed in 316 children with ASD and 227 healthy controls. Phenotypic associations were evaluated by Childhood Autism Rating Scale (CARS). Gene expression levels were measured by quantitative real-time PCR. ASD probands showed a higher frequency of "A" allele for rs7180158, "G" allele for rs12901555, and "T" allele for rs35399885. The GA + AA genotypes (rs7180158) and CT + TT genotypes (rs35399885) were found to confer significant risk towards ASD. rs2081648 was found to have transmission bias in the family. Additionally, these variants were found to be associated with one or more of ASD-associated phenotypic traits. Multifactor dimensionality reduction (MDR) analyses showed mostly independent contributory effects of some of the variants. Again, the gene expression levels of GABRB3, GABRG3, and GABRA5 were downregulated in the cases than the controls. ForGABRA5 rs35399885, the CC genotypes corresponded to higher expression levels compared to the other groups. This study reveals that genetic variants of GABAA receptor subunit genes are significantly associated with ASD. No data for the mentioned variants are found in the population of West Bengal, India.

Biased cultural transmission of a social custom in chimpanzees.

Cultural transmission studies in animals have predominantly focused on identifying between-group variation in tool-use techniques, while immaterial cultures remain understudied despite their potential for highlighting similarities between human and animal culture. Here, using long-term data from two chimpanzee communities, we tested whether one of chimpanzees' most enigmatic social customs-the grooming handclasp-is culturally transmitted by investigating the influence of well-documented human transmission biases on their variational preferences. After identifying differences in style preferences between the communities, we show that older and dominant individuals exert more influence over their partners' handclasp styles. Mothers were equally likely to influence their offspring's preferences as nonkin, indicating that styles are transmitted both vertically and obliquely. Last, individuals gradually converged on the group style, suggesting that conformity guides chimpanzees' handclasp preferences. Our findings show that chimpanzees' social lives are influenced by cultural transmission biases that hitherto were thought to be uniquely human.

LRRTM3 Genetic Variations, rs1925575, and rs1925608 Contributed to Autism Spectrum Disorder Trait Severity: An Observation in The Indian Probands.

Surface proteins containing leucine-rich repeat (LRR) are essential for the formation of synapses. Therefore, proteins containing aberrant LRR regions are speculated to cause synaptic dysfunction, an abnormality often associated with Autism spectrum disorder (ASD). LRR transmembrane 3 (LRRTM3) genetic variants showed association with ASD in the Caucasoid probands. We for the first time, analyzed two LRRTM3 genetic variants, rs1925575, and rs1925608, in Indian subjects (N=1048), including ASD probands (N=270), their parents (N=428), and healthy controls (N=350). ASD severity was assessed by the Childhood Autism Rating Scale2-standard test (CARS2-ST). Peripheral blood was collected after obtaining informed written consent for participation, and target sites were amplified by polymerase chain reaction using genomic DNA. Amplicons generated were subjected to differential digestion using a restriction enzyme, and the genotype data were analyzed for association with ASD by both population and family-based methods. Frequencies of rs1925608 and rs1925575 "CC" genotypes and C-C haplotype were higher in the probands (P=0.001). Analysis of parental data revealed a higher frequency of rs1925575 "T" in the fathers (P=0.01) and biased paternal transmission of rs1925575 "C" allele (P=0.03). The "Activity level" was higher in the ASD probands having rs1925608 "CC". Additionally, the score for "Relating to people" was higher in the presence of rs1925575 "TC" genotypes. The gender-based stratified analysis revealed the influence of the variants on a higher number of traits of the female probands. This pilot investigation indicated an influence of LRRTM3 genetic variants on the trait severity of Indian ASD probands.

The mutational dynamics of short tandem repeats in large, multigenerational families

BackgroundShort tandem repeats (STRs) compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. To estimate the genome-wide pattern of mutations at STR loci, we analyze blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. These pedigrees contain both sets of grandparents, the parents, and an average of 9 grandchildren per family.ResultsWe use HipSTR to identify de novo STR mutations in the 2nd generation of these pedigrees and require transmission to the third generation for validation. Analyzing approximately 1.6 million STR loci, we estimate the empirical de novo STR mutation rate to be 5.24 × 10−5 mutations per locus per generation. Perfect repeats mutate about 2 × more often than imperfect repeats. De novo STRs are significantly enriched in Alu elements.ConclusionsApproximately 30% of new STR mutations occur within Alu elements, which compose only 11% of the genome, but only 10% are found in LINE-1 insertions, which compose 17% of the genome. Phasing these mutations to the parent of origin shows that parental transmission biases vary among families. We estimate the average number of de novo genome-wide STR mutations per individual to be approximately 85, which is similar to the average number of observed de novo single nucleotide variants.

Meiotic transmission patterns of additional genomic elements in Brachionus asplanchnoidis, a rotifer with intraspecific genome size variation

Intraspecific genome size (GS) variation in Eukaryotes is often mediated by additional, nonessential genomic elements. Physically, such additional elements may be represented by supernumerary (B-)chromosomes or by large heterozygous insertions into the regular chromosome set. Here we analyze meiotic transmission patterns of Megabase-sized, independently segregating genomic elements (ISEs) in Brachionus asplanchnoidis, a planktonic rotifer that displays an up to two-fold intraspecific GS variation due to variation in size and number of these elements. To gain insights into the meiotic transmission patterns of ISEs, we measured GS distributions of haploid males produced by individual mother clones using flow cytometry and compared these distributions to theoretical distributions expected under a range of scenarios. These scenarios considered transmission biases resembling (meiotic) drive, or cosegregation biases, e.g., if pairs of ISEs preferentially migrated towards the same pole during meiosis. We found that the inferred transmission patterns were diverse and ranged from positive biases (suggesting drive) to negative biases (suggesting drag), depending on rotifer clone and its ISE composition. Additionally, we obtained evidence for a negative cosegregation bias in some of the rotifer clones, i.e., pairs of ISEs exhibited an increased probability of migrating towards opposite poles during meiosis. Strikingly, these transmission and segregation patterns were more similar among members of a genetically homogeneous inbred line than among outbred members of the population. Comparisons between early and late stages of haploid male embryonic development (e.g., young synchronized male eggs vs. hatched males) showed very similar GS distributions, suggesting that transmission biases occur very early in male development, or even during meiosis. Very large genome size was associated with reduced male embryonic survival, suggesting that excessive amounts of ISEs might be detrimental to male fitness. Altogether, our results indicate considerable functional diversity of ISEs in B. asplanchnoidis, with consequences on meiotic transmission and embryonic survival.

Combining Conformist and Payoff Bias in Cultural Evolution : An Integrated Model for Human Decision-Making.

Most research on transmission biases in cultural evolution has treated different biases as distinct strategies. Here I present a model that combines both frequency dependent bias (including conformist bias) and payoff bias in a single decision-making calculus and show that such an integrated learning strategy may be superior to relying on either bias alone. Natural selection may operate on humans' relative dependence on frequency and payoff information, but both are likely to contribute to the spread of variants with high payoffs. Importantly, the magnitude of conformist bias affects the evolutionary dynamics, and I show that an intermediate level of conformity may be most adaptive and may spontaneously evolve as it resists the invasion of low-payoff variants yet enables the fixation of high-payoff variants in the population.

Assessment of Active Dopants and p-n Junction Abruptness Using In Situ Biased 4D-STEM.

A key issue in the development of high-performance semiconductor devices is the ability to properly measure active dopants at the nanometer scale. In a p-n junction, the abruptness of the dopant profile around the metallurgical junction directly influences the electric field. Here, a contacted nominally symmetric and highly doped (NA = ND = 9 × 1018 cm-3) silicon p-n specimen is studied through in situ biased four-dimensional scanning transmission electron microscopy (4D-STEM). Measurements of electric field, built-in voltage, depletion region width, and charge density are combined with analytical equations and finite-element simulations in order to evaluate the quality of the junction interface. It is shown that all the junction parameters measured are compatible with a linearly graded junction. This hypothesis is also consistent with the evolution of the electric field with bias as well as off-axis electron holography data. These results demonstrate that in situ biased 4D-STEM can allow a better understanding of the electrostatics of semiconductor p-n junctions with nm-scale resolution.

Leveraging a natural murine meiotic drive to suppress invasive populations

Invasive rodents are a major cause of environmental damage and biodiversity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate a gene drive strategy (tCRISPR) that leverages super-Mendelian transmission of the t haplotype to spread inactivating mutations in a haplosufficient female fertility gene (Prl). Using spatially explicit individual-based in silico modeling, we show that tCRISPR can eradicate island populations under a range of realistic field-based parameter values. We also engineer transgenic tCRISPR mice that, crucially, exhibit biased transmission of the modified t haplotype and Prl mutations at levels our modeling predicts would be sufficient for eradication. This is an example of a feasible gene drive system for invasive alien rodent population control.

Athermal Microwave Photonic Sensor Based on Single Microring Resonance Assisted by Machine Learning

We propose a machine learning (ML) assisted athermal microwave photonic (MWP) sensing scheme with high resolution based on a single microring resonance. The immunity of temperature interference of the high-resolution sensing is achieved by employing MWP sideband processing based interrogation, and supervised machine learning based on support vector regression (SVR) and neural tangent kernel (NTK) that are effective on small datasets. The MWP sideband processing transforms the variation of the target measurand into the shift of an ultra-deep notch in the radio frequency (RF) spectrum relieving the fabrication requirements on the microresonators, while ML accurately predicts the measurand by using the modulator bias voltage or RF passband transmission together with the RF notch position. The proposed sensor is demonstrated for relative humidity (RH) measurements using a silicon-on-insulator microring coated with polymethyl methacrylate. About 50 dB high RF rejection ratio is achieved over the sensing process, indicating a high sensing resolution. Despite the small experimental datasets, the established SVR and NTK models consistently exhibit lower mean absolute errors (MAEs) than the linear regression model in the RH prediction in the presence of temperature drifts. The NTK models achieve the lowest MAEs of 1.01% RH and 1.03% RH when the RF passband transmission and modulator bias are selected as the model input, respectively. The equivalent performances of the RF passband transmission and modulator bias voltage further demonstrate the feasibility of athermal sensing based solely on the MWP interrogation results of a single microring resonance, which simplifies the design and reduces the complexity.

Post-treatment symptomatic improvement of the eastern Indian ADHD probands is influenced by CYP2D6 genetic variations.

Symptomatic remediation from attention deficit hyperactivity disorder (ADHD)-associated traits is achieved by treatment with methylphenidate (MPH)/atomoxetine (ATX). We have analyzed the association of functional CYP2D6 variations, rs1065852, rs3892097, rs1135840, and rs1058164, with ADHD in the Indian subjects. Subjects were recruited following the Diagnostic and Statistical Manual for Mental Disorders. Trait scores were obtained from the Conner's Parents Rating Scale-Revised. After obtaining informed consent, blood was collected for DNA isolation, and genotyping was performed by PCR or TaqMan-based methods. Probands were treated with MPH or ATX based on age, symptoms, and drug availability. Treatment outcome was assessed using a structured questionnaire. Data obtained was analyzed to identify the association of CYP2D6 variations and the SLC6A3 rs28363170 with the treatment outcome. The frequency of rs1135840 "G" and rs1065852 "G" was higher in the male ADHD probands. Bias in parental transmission (p=0.007) and association with higher trait scores were observed for rs1065852 "A". Independent influence of rs1065852 on ADHD was also observed. Probands carrying rs1065852 'GG', rs1135840 'CG', and rs28363170 10R exhibited significant symptomatic improvement with MPH, while probands with rs1135840 'CC' and rs28363170 9R showed improvement after ATX treatment. ADHD probands having specific CYP2D6 genetic variations respond differentially to pharmaceutical intervention.

Tracking changes in SARS-CoV-2 transmission with a novel outpatient sentinel surveillance system in Chicago, USA

Public health indicators typically used for COVID-19 surveillance can be biased or lag changing community transmission patterns. In this study, we investigate whether sentinel surveillance of recently symptomatic individuals receiving outpatient diagnostic testing for SARS-CoV-2 could accurately assess the instantaneous reproductive number R(t) and provide early warning of changes in transmission. We use data from community-based diagnostic testing sites in the United States city of Chicago. Patients tested at community-based diagnostic testing sites between September 2020 and June 2021, and reporting symptom onset within four days preceding their test, formed the sentinel population. R(t) calculated from sentinel cases agreed well with R(t) from other indicators. Retrospectively, trends in sentinel cases did not precede trends in COVID-19 hospital admissions by any identifiable lead time. In deployment, sentinel surveillance held an operational recency advantage of nine days over hospital admissions. The promising performance of opportunistic sentinel surveillance suggests that deliberately designed outpatient sentinel surveillance would provide robust early warning of increasing transmission.

Within-population song evolution in white-throated sparrows (Zonotrichia albicollis)

Abstract Cultural evolution of birdsong occurs when songs change over generations and such changes can spread directionally or via drift within populations. We describe the emergence and directional spread of a novel song variant within a population of White-throated Sparrows in central British Columbia, Canada. Birds in this population have been singing a doublet-ending song since the early 2000s. In 2015, we detected a novel variant, consisting of a doublet-ending song with a distinctive amplitude modulation in the first note (Modulated-Doublet). We banded and recorded birds from 2015 to 2020 and classified songs using both audio and spectrographic analysis. The proportion of birds singing the Modulated-Doublet increased, replacing the Unmodulated-Doublet over time. Additionally, the modulation became more pronounced, both across the population and within individual birds, over successive years. The rapid spread suggests there may be several transmission biases driving the adoption of this novel song over the older established variant.

Meiotic drive in house mice: mechanisms, consequences, and insights for human biology.

Meiotic drive occurs when one allele at a heterozygous site cheats its way into a disproportionate share of functional gametes, violating Mendel's law of equal segregation. This genetic conflict typically imposes a fitness cost to individuals, often by disrupting the process of gametogenesis. The evolutionary impact of meiotic drive is substantial, and the phenomenon has been associated with infertility and reproductive isolation in a wide range of organisms. However, cases of meiotic drive in humans remain elusive, a finding that likely reflects the inherent challenges of detecting drive in our species rather than unique features of human genome biology. Here, we make the case that house mice (Mus musculus) present a powerful model system to investigate the mechanisms and consequences of meiotic drive and facilitate translational inferences about the scope and potential mechanisms of drive in humans. We first detail how different house mouse resources have been harnessed to identify cases of meiotic drive and the underlying mechanisms utilized to override Mendel's rules of inheritance. We then summarize the current state of knowledge of meiotic drive in the mouse genome. We profile known mechanisms leading to transmission bias at several established drive elements. We discuss how a detailed understanding of meiotic drive in mice can steer the search for drive elements in our own species. Lastly, we conclude with a prospective look into how new technologies and molecular tools can help resolve lingering mysteries about the prevalence and mechanisms of selfish DNA transmission in mammals.

A structured model and likelihood approach to estimate yeast prion propagon replication rates and their asymmetric transmission.

Prion proteins cause a variety of fatal neurodegenerative diseases in mammals but are generally harmless to Baker’s yeast (Saccharomyces cerevisiae). This makes yeast an ideal model organism for investigating the protein dynamics associated with these diseases. The rate of disease onset is related to both the replication and transmission kinetics of propagons, the transmissible agents of prion diseases. Determining the kinetic parameters of propagon replication in yeast is complicated because the number of propagons in an individual cell depends on the intracellular replication dynamics and the asymmetric division of yeast cells within a growing yeast cell colony. We present a structured population model describing the distribution and replication of prion propagons in an actively dividing population of yeast cells. We then develop a likelihood approach for estimating the propagon replication rate and their transmission bias during cell division. We first demonstrate our ability to correctly recover known kinetic parameters from simulated data, then we apply our likelihood approach to estimate the kinetic parameters for six yeast prion variants using propagon recovery data. We find that, under our modeling framework, all variants are best described by a model with an asymmetric transmission bias. This demonstrates the strength of our framework over previous formulations assuming equal partitioning of intracellular constituents during cell division.

Communication-Enhancing Vagueness

I experimentally investigate how vague language changes the nature of communication in a biased strategic information transmission game. Counterintuitively, when both precise and imprecise messages can be sent, in aggregate, senders are more accurate, and receivers trust them more than when only precise messages can be sent. I also develop and structurally estimate a model showing that vague messages increase communication between boundedly rational players, especially if some senders are moderately honest. Moderately honest senders avoid stating an outright lie by using vague messages to hedge them. Then, precise messages are more informative because there are fewer precise lies.

Echo chambers and information transmission biases in homophilic and heterophilic networks

We study how information transmission biases arise by the interplay between the structural properties of the network and the dynamics of the information in synthetic scale-free homophilic/heterophilic networks. We provide simple mathematical tools to quantify these biases. Both Simple and Complex Contagion models are insufficient to predict significant biases. In contrast, a Hybrid Contagion model—in which both Simple and Complex Contagion occur—gives rise to three different homophily-dependent biases: emissivity and receptivity biases, and echo chambers. Simulations in an empirical network with high homophily confirm our findings. Our results shed light on the mechanisms that cause inequalities in the visibility of information sources, reduced access to information, and lack of communication among distinct groups.