The admixed brushtail possum genome reveals invasion history in New Zealand and novel imprinted genes.

Combining genome assembly with population and functional genomics can provide valuable insights to development and evolution, as well as tools for species management. Here, we present a chromosome-level genome assembly of the common brushtail possum (Trichosurus vulpecula), a model marsupial threatened in parts of their native range in Australia, but also a major introduced pest in New Zealand. Functional genomics reveals post-natal activation of chemosensory and metabolic genes, reflecting unique adaptations to altricial birth and delayed weaning, a hallmark of marsupial development. Nuclear and mitochondrial analyses trace New Zealand possums to distinct Australian subspecies, which have subsequently hybridised. This admixture allowed phasing of parental alleles genome-wide, ultimately revealing at least four genes with imprinted, parent-specific expression not yet detected in other species (MLH1, EPM2AIP1, UBP1 and GPX7). We find that reprogramming of possum germline imprints, and the wider epigenome, is similar to eutherian mammals except onset occurs after birth. Together, this work is useful for genetic-based control and conservation of possums, and contributes to understanding of the evolution of novel mammalian epigenetic traits.

Comparison of Reptilian Genomes Reveals Deletions Associated with the Natural Loss of γδ T Cells in Squamates.

T lymphocytes or T cells are key components of the vertebrate response to pathogens and cancer. There are two T cell classes based on their TCRs, αß T cells and γδ T cells, and each plays a critical role in immune responses. The squamate reptiles may be unique among the vertebrate lineages by lacking an entire class of T cells, the γδ T cells. In this study, we investigated the basis of the loss of the γδ T cells in squamates. The genome and transcriptome of a sleepy lizard, the skink Tiliqua rugosa, were compared with those of tuatara, Sphenodon punctatus, the last living member of the Rhynchocephalian reptiles. We demonstrate that the lack of TCRγ and TCRδ transcripts in the skink are due to large deletions in the T. rugosa genome. We also show that tuataras are on a growing list of species, including sharks, frogs, birds, alligators, and platypus, that can use an atypical TCRδ that appears to be a chimera of a TCR chain with an Ab-like Ag-binding domain. Tuatara represents the nearest living relative to squamates that retain γδ T cells. The loss of γδTCR in the skink is due to genomic deletions that appear to be conserved in other squamates. The genes encoding the αßTCR chains in the skink do not appear to have increased in complexity to compensate for the loss of γδ T cells.

Genome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort.

Cannabis use is of increasing public health interest globally. Here we examined the effect of heavy cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study, CHDS). A total of 48 heavy cannabis users were selected from the CHDS cohort, on the basis of their adult exposure to cannabis and tobacco, and DNA methylation assessed from whole blood samples, collected at approximately age 28. Methylation in heavy cannabis users was assessed, relative to non-users (n = 48 controls) via the Illumina Infinium® MethylationEPIC BeadChip. We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenome-wide significance level (P < 10-7). However, there were 521 sites differentially methylated at P < 0.001 which were enriched for genes involved in neuronal signalling (glutamatergic synapse and long-term potentiation) and cardiomyopathy. Further, the most differentially methylated loci were associated with genes with reported roles in brain function (e.g. TMEM190, MUC3L, CDC20 and SP9). We conclude that the effects of cannabis use on the mature human blood methylome differ from, and are less pronounced than, the effects of tobacco use, and that larger sample sizes are required to investigate this further.

Stress, novel sex genes, and epigenetic reprogramming orchestrate socially controlled sex change.

Bluehead wrasses undergo dramatic, socially cued female-to-male sex change. We apply transcriptomic and methylome approaches in this wild coral reef fish to identify the primary trigger and subsequent molecular cascade of gonadal metamorphosis. Our data suggest that the environmental stimulus is exerted via the stress axis and that repression of the aromatase gene (encoding the enzyme converting androgens to estrogens) triggers a cascaded collapse of feminizing gene expression and identifies notable sex-specific gene neofunctionalization. Furthermore, sex change involves distinct epigenetic reprogramming and an intermediate state with altered epigenetic machinery expression akin to the early developmental cells of mammals. These findings reveal at a molecular level how a normally committed developmental process remains plastic and is reversed to completely alter organ structures.

Stress and sex: does cortisol mediate sex change in fish?

Cortisol is the main glucocorticoid (GC) in fish and the hormone most directly associated with stress. Recent research suggests that this hormone may act as a key factor linking social environmental stimuli and the onset of sex change by initiating a shift in steroidogenesis from estrogens to androgens. For many teleost fish, sex change occurs as a usual part of the life cycle. Changing sex is known to enhance the lifetime reproductive success of these fish and the modifications involved (behavioral, gonadal and morphological) are well studied. However, the exact mechanism behind the transduction of the environmental signals into the molecular cascade that underlies this singular process remains largely unknown. We here synthesize current knowledge regarding the role of cortisol in teleost sex change with a focus on two well-described transformations: temperature-induced masculinization and socially regulated sex change. Three non-mutually exclusive pathways are considered when describing the potential role of cortisol in mediating teleost sex change: cross-talk between GC and androgen pathways, inhibition of aromatase expression and upregulation of amh (the gene encoding anti-Müllerian hormone). We anticipate that understanding the role of cortisol in the initial stages of sex change will further improve our understanding of sex determination and differentiation across vertebrates, and may lead to new tools to control fish sex ratios in aquaculture.

mtDNA polymorphism and metabolic inhibition affect sperm performance in conplastic mice.

Whereas a broad link exists between nucleotide substitutions in the mitochondrial genome (mtDNA) and a range of metabolic pathologies, exploration of the effect of specific mtDNA genotypes is on-going. Mitochondrial DNA mutations are of particular relevance for reproductive traits, since they are expected to have profound effects on male specific processes as a result of the strict maternal inheritance of mtDNA. Sperm motility is crucially dependent on ATP in most systems studied. However, the importance of mitochondrial function in the production of the ATP necessary for sperm function remains uncertain. In this study, we test the effect of mtDNA polymorphisms upon mouse sperm performance and bioenergetics by using five conplastic inbred strains that share the same nuclear background while differing in their mitochondrial genomes. We found that, while genetic polymorphisms across distinct mtDNA haplotypes are associated with modification in sperm progressive velocity, this effect is not related to ATP production. Furthermore, there is no association between the number of mtDNA polymorphisms and either (a) the magnitude of sperm performance decrease, or (b) performance response to specific inhibition of the main sperm metabolic pathways. The observed variability between strains may be explained in terms of additive effects of single nucleotide substitutions on mtDNA coding sequences, which have been stabilized through genetic drift in the different laboratory strains. Alternatively, the decreased sperm performance might have arisen from the disruption of the nuclear DNA/mtDNA interactions that have coevolved during the radiation of Mus musculus subspecies.

Microsatellite polymorphisms associated with human behavioural and psychological phenotypes including a gene-environment interaction.

BACKGROUND: The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies. METHODS: We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied longitudinal birth cohort (n = 458-589) using one way analysis of variance. The repeats were a highly conserved poly-AC microsatellite in the upstream promoter region of the T-box brain 1 (TBR1) gene and three previously studied STRs in the activating enhancer-binding protein 2-beta (AP2-ß) and androgen receptor (AR) genes. Where significance was found we used multiple regression to assess the influence of confounding factors. RESULTS: Carriers of the shorter, most common, allele of the AR gene's GGN microsatellite polymorphism had fewer anxiety-related symptoms, which was consistent with previous studies, but in our study this was not significant following Bonferroni correction. No associations with two repeats in the AP2-ß gene withstood this correction. A novel finding was that carriers of the minor allele of the TBR1 AC microsatellite were at higher risk of conduct problems in childhood at age 7-9 (p = 0.0007, which did pass Bonferroni correction). Including maternal smoking during pregnancy (MSDP) in models controlling for potentially confounding influences showed that an interaction between TBR1 genotype and MSDP was a significant predictor of conduct problems in childhood and adolescence (p < 0.001), and of self-reported criminal behaviour up to age 25 years (p ≤ 0.02). This interaction remained significant after controlling for possible confounders including maternal age at birth, socio-economic status and education, and offspring birth weight. CONCLUSIONS: The potential functional importance of the TBR1 gene's promoter microsatellite deserves further investigation. Our results suggest that it participates in a gene-environment interaction with MDSP and antisocial behaviour. However, previous evidence that mothers who smoke during pregnancy carry genes for antisocial behaviour suggests that epistasis may influence the interaction.

Sexual plasticity: A fishy tale.

Teleost fish exhibit remarkably diverse and plastic patterns of sexual development. One of the most fascinating modes of plasticity is functional sex change, which is widespread in marine fish including species of commercial importance; however, the regulatory mechanisms remain elusive. In this review, we explore such sexual plasticity in fish, using the bluehead wrasse (Thalassoma bifasciatum) as the primary model. Synthesizing current knowledge, we propose that cortisol and key neurochemicals modulate gonadotropin releasing hormone and luteinizing hormone signaling to promote socially controlled sex change in protogynous fish. Future large-scale genomic analyses and systematic comparisons among species, combined with manipulation studies, will likely uncover the common and unique pathways governing this astonishing transformation. Revealing the molecular and neuroendocrine mechanisms underlying sex change in fish will greatly enhance our understanding of vertebrate sex determination and differentiation as well as phenotypic plasticity in response to environmental influences. Mol. Reprod. Dev. 84: 171-194, 2017. © 2016 Wiley Periodicals, Inc.

Inheritance of telomere length in a bird.

Telomere dynamics are intensively studied in human ageing research and epidemiology, with many correlations reported between telomere length and age-related diseases, cancer and death. While telomere length is influenced by environmental factors there is also good evidence for a strong heritable component. In human, the mode of telomere length inheritance appears to be paternal and telomere length differs between sexes, with females having longer telomeres than males. Genetic factors, e.g. sex chromosomal inactivation, and non-genetic factors, e.g. antioxidant properties of oestrogen, have been suggested as possible explanations for these sex-specific telomere inheritance and telomere length differences. To test the influence of sex chromosomes on telomere length, we investigated inheritance and sex-specificity of telomere length in a bird species, the kakapo (Strigops habroptilus), in which females are the heterogametic sex (ZW) and males are the homogametic (ZZ) sex. We found that, contrary to findings in humans, telomere length was maternally inherited and also longer in males. These results argue against an effect of sex hormones on telomere length and suggest that factors associated with heterogamy may play a role in telomere inheritance and sex-specific differences in telomere length.

Adaptive radiation within New Zealand endemic species of the cockroach genus Celatoblatta Johns (Blattidae): a response to Plio-Pleistocene mountain building and climate change.

The South Island of New Zealand offers unique opportunities to study insect evolution due to long-term physical isolation, recent alpine habitats and high levels of biotic endemism. Using DNA sequence data from cytochrome oxidase subunit 1, we investigated the phylogeographical pattern among 10 endemic cockroach species within the genus Celatoblatta Johns (Blattidae). We tested the hypothesis that an ancestral cockroach species underwent rapid speciation in response to major climatic differentiation induced by mountain building. Results suggest that speciation was a twofold process, with an interspecific radiation of Pliocene/Pleistocene age followed by intraspecific diversification during the mid Pleistocene. Average genetic distance (maximum likelihood GTR + I + Gamma) was 9.17%, with a maximum of 14.5%. Data revealed eight deep well-supported branches, each with terminal clades. Six clades were differentiated according to morphological species, while the seventh was composed of three sympatric species. We consider the latter to be a phylogenetic species, possibly as a result of hybridization within a defined geographical area. This finding seriously challenges species distinctions for these three cockroach species. Correlation between genetic distances and a Climate Similarity Index (CSI) was negative, suggesting that species found in similar habitats are also genetically closely related. A Mantel test on within-clade genetic distances vs. linear geographical distance was positive, suggesting allopatric isolation for those haplotypes. We present a model of speciation for South Island Celatoblatta.

Mother's curse: the effect of mtDNA on individual fitness and population viability.

The mitochondrial genome is considered generally to be an innocent bystander in adaptive evolution; however, there is increasing evidence that mitochondrial DNA (mtDNA) is an important contributor to viability and fecundity. Some of this evidence is now well documented, with mtDNA mutations having been shown to play a causal role in degenerative diseases, ageing, and cancer. However, most research on mtDNA has ignored the possibility that other instances exist where mtDNA mutations could have profound fitness consequences. Recent work in humans and other species now indicates that mtDNA mutations play an important role in sperm function, male fertility, and male fitness. Ironically, deleterious mtDNA mutations that affect only males, such as those that impair sperm function, will not be subject to natural selection because mitochondria are generally maternally inherited and could reach high frequencies in populations if the mutations are not disadvantageous in females. Here, we review how such mtDNA mutations might affect the viability of natural populations. We consider factors that increase or decrease the strength of the effect of mtDNA mutations on population viability and discuss what mechanisms exist to mitigate deleterious mtDNA effects.