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Biology subjects

Parrott, B. B.

Publications and source records attributed to Parrott, B. B..

7 recordsLinked to original sources

Long-term population decline and recombination heterogeneity shape genomic diversity in the American alligator

The loss of genetic diversity caused by population bottlenecks can significantly impact the ability of a species to adapt to disease, natural disasters, and changing environments. Over the last 175, years, American alligator (A. mississippiensis) populations underwent a decline due to habitat destruction and exploitation followed by a rebound resulting from dedicated conservation efforts. Despite a current census population of millions, microsatellite data indicates a significant paucity of genetic variation within alligators. Using whole genome sequences from 19 individuals sampled from the species geographic range, we quantified nucleotide diversity, heterozygosity, inbreeding, demographic history, and fine-scale recombination rates. We find that American alligator genomes exhibit low nucleotide diversity and elevated homozygosity relative to many vertebrates, but these patterns are dominated by numerous short runs of homozygosity (ROHs), rather than long tracts indicative of recent inbreeding. Demographic history reconstruction based on site-frequency-spectrum analyses support a prolonged decline in effective population size beginning in the last glacial period, indicating that this reduced genetic diversity largely predates intensive human exploitation. Additionally, we uncover a highly structured recombination landscape, with recombination consistently elevated at distal chromosomal regions and suppressed across large central segments. This heterogeneity is associated with genomic spatial variation in nucleotide diversity, suggesting that the recombination landscape contributes to the persistence of homozygosity following population expansion. Together, our results highlight that demographic recovery does not necessarily equate to genetic recovery and show how long-term population history and genomic architecture continue to shape diversity in a "recovered" species.

genomics↗

Co-Circulation of Multiple Kolmioviridae Lineages Through Vertebrate Evolution

Although once only characterized by human hepatitis deltavirus (HDV), membership of the family Kolmioviridae has dramatically expanded in recent years. Despite this transformation in our understanding of the host range of kolmioviruses, the evolutionary history of this enigmatic group of RNA viruses is unclear. Kolmioviruses are characterized as small ([~]1.7kb) satellite viruses that encode a single [~]200 amino acid delta antigen (DAg) and require unrelated helper viruses for replication. Here, we describe eight novel kolmioviruses from metatranscriptomic studies of the American alligator (Alligator missippiensis), red kangaroo (Osphranter rufus), and central bearded dragon (Pogona vitticeps), as well as avian kolmioviruses mined from the Sequence Read Archive (SRA). Although the novel kolmioviruses were often found in samples co-infected by other viruses, there was no evidence for the presence of hepatitis B virus as seen in HDV. By employing a range of sequence data sets, alignment methods, alignment trimming methods, and substitution models, we provide an evolutionary history of the Kolmioviridae that maximizes the extent of virus-host co-divergence and refines estimates of their evolutionary timescale. Although DAg amino acid sequences are more conserved than nucleotide sequences and hence might be expected to result in more accurate phylogenetic trees, we show that full genome nucleotide sequences likely provide the best representation of kolmiovirus evolution. More broadly, our results reveal that irrespective of the data set used, multiple distinct kolmiovirus lineages have co-circulated throughout vertebrate evolution over timescales spanning hundreds of millions of years, with the association between HDV and HBV appearing only recently. Significance StatementKolmioviruses are satellite RNA viruses, with hepatitis deltavirus (HDV) associated with human disease following co-infection with hepatitis B virus (HBV) the best characterized. Although a growing number of animal kolmioviruses have been identified in metagenomic studies and associated with a range of helper viruses, the evolutionary origins and history of this important and unique group of viruses is unknown. By identifying novel kolmioviruses in a range vertebrate hosts, including American alligators, we show that highly diverse lineages of kolmioviruses have co-circulated for the duration of vertebrate evolution with clear evidence of virus-host co-divergence, and are associated with a variety of potential helper viruses. Despite this antiquity, we present evidence that the HDV-HBV association only recently evolved in human populations.

microbiology↗

Differential early-life survival underlies the adaptive significance of temperature-dependent sex determination in a long-lived reptile

O_LIMany ectotherms rely on temperature cues experienced during development to determine offspring sex. The first descriptions of temperature-dependent sex determination (TSD) were made over 50 years ago, yet an understanding of its adaptive significance remains elusive, especially in long-lived taxa. C_LIO_LIOne novel hypothesis predicts that TSD should be evolutionarily favored when two criteria are met - (a) incubation temperature influences annual juvenile survival and (b) sexes mature at different ages. Under these conditions, a sex-dependent effect of incubation temperature on offspring fitness arises through differences in age at sexual maturity, with the sex that matures later benefiting disproportionately from temperatures that promote juvenile survival. C_LIO_LIThe American alligator (Alligator mississippiensis) serves as an insightful model in which to test this hypothesis, as males begin reproducing nearly a decade after females. Here, through a combination of artificial incubation experiments and mark-recapture approaches, we test the specific predictions of the survival-to-maturity hypothesis for the adaptive value of TSD by disentangling the effects of incubation temperature and sex on annual survival of alligator hatchlings across two geographically distinct sites. C_LIO_LIHatchlings incubated at male-promoting temperatures consistently exhibited higher survival compared to those incubated at female-promoting temperatures. This pattern appears independent of hatchling sex, as females produced from hormone manipulation at male-promoting temperatures exhibit similar survival to their male counterparts. C_LIO_LIAdditional experiments show that incubation temperature may affect early-life survival primarily by affecting the efficiency with which maternally transferred energy resources are used during development. C_LIO_LIResults from this study provide the first explicit empirical support for the adaptive value of TSD in a crocodilian and point to developmental energetics as a potential unifying mechanism underlying persistent survival consequences of incubation temperature. C_LI

ecology↗

Age related disorder in DNA methylation patterns underlies epigenetic clock signals, but displays distinct responses to epigenetic rejuvenation events

Changes in DNA methylation with age are observed across the tree of life. The stereotypical nature of these changes can be modeled to produce epigenetic clocks capable of predicting biological age with unprecedented accuracy. Despite the predictive ability of epigenetic clocks, the underlying processes that produce clock signals are not resolved but are hypothesized to be rooted in stochastic processes leading to an erosion in the epigenetic landscape. Here, we test this hypothesis using a novel computational approach for measuring disorder in DNA methylation patterns across the epigenome. We find that loci comprising conventional epigenetic clocks are enriched in regions that both accumulate and lose disorder with age, suggesting a direct link between DNA methylation disorder and epigenetic clock signals. Across the murine lifespan, disorder accumulates in Polycomb Repressive Complex 2 target genes and decreases in CTCF and transcription factor binding sites, resulting in genomic hotspots of age-related epigenetic disorder. We further investigate the connections between age-related changes in disorder and epigenetic clock signals by comparing the influences of development, lifespan interventions, and cellular dedifferentiation using a series of newly developed epigenetic clocks based on regional disorder, average methylation states, and commonly used measures of entropy. We identify both common responses as well as critical differences between canonical epigenetic clocks and those based on regional disorder, demonstrating a fundamental decoupling of epigenetic aging processes. Collectively, this work identifies key linkages between epigenetic disorder and epigenetic clock signals, and simultaneously demonstrates the multifaceted nature of epigenetic aging in which stochastic processes occurring at non-random loci produce predictable outcomes.

genomics↗

Genome-wide DNA methylation patterns harbor signatures of hatchling sex and past incubation temperature in a species with environmental sex determination

Conservation of thermally sensitive species depends on monitoring organismal and population-level responses to environmental change in real time. Epigenetic processes are increasingly recognized as key integrators of environmental conditions into developmentally plastic responses, and attendant epigenomic datasets hold potential for revealing cryptic phenotypes relevant to conservation efforts. Here, we demonstrate the utility of genome-wide DNA methylation (DNAm) patterns in the face of climate change for a group of especially vulnerable species, those with temperature-dependent sex determination (TSD). Due to their reliance on thermal cues during development to determine sexual fate, contemporary shifts in temperature are predicted to skew offspring sex ratios and ultimately destabilize sensitive populations. Using reduced-representation bisulfite sequencing, we profiled the DNA methylome in blood cells of hatchling American alligator (Alligator mississippiensis), a TSD species lacking reliable markers of sexual dimorphism in early life-stages. We identified 120 sex-associated differentially methylated cytosines (DMCs; FDR < 0.1) in hatchlings incubated under a range of temperatures, as well as 707 unique temperature-associated DMCs. We further developed DNAm-based models capable of predicting hatchling sex with 100% accuracy and past incubation temperature with a mean absolute error of 1.2{degrees}C based on the methylation status of 20 and 24 loci, respectively. Though largely independent of epigenomic patterning occurring in the embryonic gonad during TSD, DNAm patterns in blood cells may serve as non-lethal markers of hatchling sex and past incubation conditions in conservation applications. These findings also raise intriguing questions regarding tissue-specific epigenomic patterning in the context of developmental plasticity.

genomics↗

The aging DNA methylome reveals environment-by-aging interactions in a model teleost

The rate at which individuals age underlies variation in life history and attendant health and disease trajectories. Age specific patterning of the DNA methylome ("epigenetic aging") is strongly correlated with chronological age in humans and can be modeled to produce epigenetic age predictors. However, epigenetic age estimates vary among individuals of the same age, and this mismatch is correlated to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not resolved. In an effort to develop a tractable model in which environmental drivers of epigenetic aging can be assessed, we investigate the relationship between aging and DNA methylation in a small teleost, medaka (Oryzias latipes). We find that age-associated DNA methylation patterning occurs broadly across the genome, with the majority of age-related changes occurring during early life. By modeling the stereotypical nature of age-associated DNA methylation dynamics, we built an epigenetic clock, which predicts chronological age with a mean error of 29.1 days (~4% of average lifespan). Characterization of clock loci suggests that aspects of epigenetic aging are functionally similar across vertebrates. To understand how environmental factors interact with epigenetic aging, we exposed medaka to four doses of ionizing radiation for seven weeks, hypothesizing that exposure to such an environmental stressor would accelerate epigenetic aging. While the epigenetic clock was not significantly affected, radiation exposure accelerated and decelerated patterns of normal epigenetic aging, with radiation-induced epigenetic alterations enriched at loci that become hypermethylated with age. Together, our findings advance ongoing research attempting to elucidate the functional role of DNA methylation in integrating environmental factors into the rate of biological aging.

genomics↗

G-Protein signaling increases germline stem cell activity in Drosophila males in response to multiple rounds of mating

Adult stem cells divide to renew the stem cell pool and replenish specialized cells that are lost due to death or usage. However, little is known about the mechanisms regulating how stem cells adjust to a demand for specialized cells. A failure of the stem cells to respond to this demand can have serious consequences, such as tissue loss, or prolonged recovery post injury. Here, we challenge the male germline stem cells (GSCs) of Drosophila melanogaster for the production of specialized cells using mating experiments. We show that repeated mating reduced the sperm pool and accelerated germline stem cell (GSC) divisions. The increase in GSC divisions depended on the activity of the highly conserved G-proteins. Germline expression of RNA-Interference (RNA-i) constructs against G-proteins or a dominant negative G-protein eliminated the increase in GSC divisions in mated males. Consistent with a role for the G-proteins in the regulation of GSC divisions, RNA-i against seven out of 35 G-protein coupled receptors (GPCRs) within the germline cells also eliminated the capability of males to accelerate their GSC divisions in response to mating. Our data show that GSCs are receptive to GPCR stimulus, potentially through a network of interactions among multiple signaling pathways.

developmental biology↗