Seeing is Believing: Dynamic Evolution of Gene Families

Department of Integrative Biology, Center for Computational Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712Supported by National Science Foundation Grants IOS- 0843712 and IOS-1354942 (to H.A.H.) and DBI-0939454 for the BEACON Center for the Study of Evolution in Action.Integrative Biolog

Integrating Resource Defence Theory with a Neural Nonapeptide Pathway to Explain Territory-Based Mating Systems

1 Texas Research Institute for Environmental Studies, Sam Houston State University, Huntsville, TX 77341 USA; Department of Biology, Case Western Reserve University, Cleveland, OH 44106 USA. 2 Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78712 USA. 3 Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712 USA. 4 Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712 USA.The ultimate-level factors that drive the evolution of mating systems have been well studied, but an evolutionarily conserved neural mechanism involved in shaping behaviour and social organization across species has remained elusive. Here, we review studies that have investigated the role of neural arginine vasopressin (AVP), vasotocin (AVT), and their receptor V1a in mediating variation in territorial behaviour. First, we discuss how aggression and territoriality are a function of population density in an inverted-U relationship according to resource defence theory, and how territoriality influences some mating systems. Next, we find that neural AVP, AVT, and V1a expression, especially in one particular neural circuit involving the lateral septum of the forebrain, are associated with territorial behaviour in males of diverse species, most likely due to their role in enhancing social cognition. Then we review studies that examined multiple species and find that neural AVP, AVT, and V1a expression is associated with territory size in mammals and fishes. Because territoriality plays an important role in shaping mating systems in many species, we present the idea that neural AVP, AVT, and V1a expression that is selected to mediate territory size may also influence the evolution of different mating systems. Future research that interprets proximate-level neuro-molecular mechanisms in the context of ultimate-level ecological theory may provide deep insight into the brain-behaviour relationships that underlie the diversity of social organization and mating systems seen across the animal kingdom.This work was supported by an Engineering Plus NSF-ADVANCE Opportunity grant to R.G. O., and NSF Grants IOS-0843712 and IOS-1354942, an Alfred P. Sloan Foundation Fellowship, the Dwight W. and Blanche Faye Reeder Centennial Fellowship in Systematic and Evolutionary Biology, and an Institute for Cellular and Molecular Biology Fellowship to H.A.H.Integrative Biolog

Inhibition of Aromatase Induces Partial Sex Change in a Cichlid Fish: Distinct Functions for Sex Steroids in Brains and Gonads

Sex steroids are major drivers of sexual development and also responsible for the maintenance of the established gender. Especially fishes exhibit great plasticity and less conservation in sex determination and sexual development compared to other vertebrate groups. In addition, fishes have a constant sex steroid production throughout their entire lifespan, which makes them particularly susceptible to interferences with the endogenous sex steroid system. This susceptibility has recently been used to show that inhibition of the key enzyme of estrogen synthesis, aromatase Cyp19a1, can induce functional sex reversal even in adult fish. Here, we investigated the impact of the aromatase inhibitor (AI) fadrozole in adult females of the East African cichlid fish Astatotilapia burtoni. Using gene expression, phenotypic measurements, behavioral experiments, and hormone measurements, we assessed if females treated with fadrozole develop a male-like phenotype. We found that AI treatment has a different effect on gene expression in the gonad compared to the brain, the 2 tissues mostly implicated in sexual development. In contrast to observations in other gonochoristic species, A. burtoni ovaries cannot be transformed into functional testis by AI. However, rapid changes towards a male-like phenotype can be induced with AI in coloration, hormone levels, and behavior

Social odors conveying dominance and reproductive information induce rapid physiological and neuromolecular changes in a cichlid fish

Background: Social plasticity is a pervasive feature of animal behavior. Animals adjust the expression of their social behavior to the daily changes in social life and to transitions between life-history stages, and this ability has an impact in their Darwinian fitness. This behavioral plasticity may be achieved either by rewiring or by biochemically switching nodes of the neural network underlying social behavior in response to perceived social information. Independent of the proximate mechanisms, at the neuromolecular level social plasticity relies on the regulation of gene expression, such that different neurogenomic states emerge in response to different social stimuli and the switches between states are orchestrated by signaling pathways that interface the social environment and the genotype. Here, we test this hypothesis by characterizing the changes in the brain profile of gene expression in response to social odors in the Mozambique Tilapia, Oreochromis mossambicus. This species has a rich repertoire of social behaviors during which both visual and chemical information are conveyed to conspecifics. Specifically, dominant males increase their urination frequency during agonist encounters and during courtship to convey chemical information reflecting their dominance status. Results: We recorded electro-olfactograms to test the extent to which the olfactory epithelium can discriminate between olfactory information from dominant and subordinate males as well as from pre- and post-spawning females. We then performed a genome-scale gene expression analysis of the olfactory bulb and the olfactory cortex homolog in order to identify the neuromolecular systems involved in processing these social stimuli. Conclusions: Our results show that different olfactory stimuli from conspecifics' have a major impact in the brain transcriptome, with different chemical social cues eliciting specific patterns of gene expression in the brain. These results confirm the role of rapid changes in gene expression in the brain as a genomic mechanism underlying behavioral plasticity and reinforce the idea of an extensive transcriptional plasticity of cichlid genomes, especially in response to rapid changes in their social environment.Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [EXCL/BIA-ANM/0549/2012, Pest-OE/MAR/UI0331/2011]; Dwight W. and Blanche Faye Reeder Centennial Fellowship in Systematic and Evolutionary Biology; Institute for Cellular and Molecular Biology Fellowship; FCTinfo:eu-repo/semantics/publishedVersio

The genomic substrate for adaptive radiation in African cichlid fish

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification

Polygenic Risk Modelling for Prediction of Epithelial Ovarian Cancer Risk

Funder: Funding details are provided in the Supplementary MaterialAbstractPolygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28–1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08–1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30–1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.</jats:p

Integrating Resource Defence Theory with a Neural Nonapeptide Pathway to Explain Territory-Based Mating Systems

1 Texas Research Institute for Environmental Studies, Sam Houston State University, Huntsville, TX 77341 USA; Department of Biology, Case Western Reserve University, Cleveland, OH 44106 USA. 2 Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78712 USA. 3 Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712 USA. 4 Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712 USA.The ultimate-level factors that drive the evolution of mating systems have been well studied, but an evolutionarily conserved neural mechanism involved in shaping behaviour and social organization across species has remained elusive. Here, we review studies that have investigated the role of neural arginine vasopressin (AVP), vasotocin (AVT), and their receptor V1a in mediating variation in territorial behaviour. First, we discuss how aggression and territoriality are a function of population density in an inverted-U relationship according to resource defence theory, and how territoriality influences some mating systems. Next, we find that neural AVP, AVT, and V1a expression, especially in one particular neural circuit involving the lateral septum of the forebrain, are associated with territorial behaviour in males of diverse species, most likely due to their role in enhancing social cognition. Then we review studies that examined multiple species and find that neural AVP, AVT, and V1a expression is associated with territory size in mammals and fishes. Because territoriality plays an important role in shaping mating systems in many species, we present the idea that neural AVP, AVT, and V1a expression that is selected to mediate territory size may also influence the evolution of different mating systems. Future research that interprets proximate-level neuro-molecular mechanisms in the context of ultimate-level ecological theory may provide deep insight into the brain-behaviour relationships that underlie the diversity of social organization and mating systems seen across the animal kingdom.This work was supported by an Engineering Plus NSF-ADVANCE Opportunity grant to R.G. O., and NSF Grants IOS-0843712 and IOS-1354942, an Alfred P. Sloan Foundation Fellowship, the Dwight W. and Blanche Faye Reeder Centennial Fellowship in Systematic and Evolutionary Biology, and an Institute for Cellular and Molecular Biology Fellowship to H.A.H.Integrative Biolog

Stress-mediated convergence of splicing landscapes in male and female rock doves

BackgroundThe process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothalamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes.ResultsThis study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, after subjecting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3'UTR (untranslated region) end of transcripts than the 5'UTR or coding regions.ConclusionsOur results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stress-induced reproductive dysfunction