Biology subjects

Johnson, P. L. F.

Publications and source records attributed to Johnson, P. L. F..

7 recordsLinked to original sources

bioRxiv2026

ZBTB7B is a Master Regulator of Salivary Acinar Cell Function

Salivary glands exhibit transcriptional programs that distinguish them from other tissues, yet the upstream regulatory logic underlying these programs is not well defined. To identify transcription factors (TFs) that structure salivary identity, we generated RNA-seq and ATAC-seq from human major and minor salivary glands and inferred TF[->]TF regulatory edges from high-confidence chromatin footprints. ZBTB7B emerged as the most connected regulator across salivary samples. To locate regulatory regions associated with salivary-specific transcription, we trained hidden Markov models (HMMs) on chromatin accessibility across 4 Mbp windows surrounding salivary-specific and non-salivary-specific transcription start sites. The resulting chromatin states distinguished promoter-proximal openness from distal enhancer activity and identified salivary-specific enhancers enriched for ZBTB7B motifs. These enhancer states correlated strongly with expression of salivary genes, including AQP5, indicating that distal regulation contributes substantially to salivary transcriptional specificity. To assess the consequences of losing Zbtb7b, we performed single-cell RNA-seq and spatial transcriptomics on submandibular and parotid glands from Zbtb7b knockout mice. Knockout mice exhibited reduced salivary flow, shifts in acinar cell proportions, and the emergence of a neonate-like acinar population characterized by loss of canonical secreted proteins and increased expression of MHC class I genes. These transcriptional and cellular changes occurred despite preserved gland architecture, suggesting that Zbtb7b stabilizes adult acinar identity rather than supporting structural maintenance. Together, these data identify ZBTB7B as a master regulator of salivary transcriptional networks, acting through both promoter-proximal and enhancer-level mechanisms, and demonstrate that loss of Zbtb7b disrupts acinar identity and impairs salivary function.

genomics↗

bioRxiv2026

Can the Z:A ratio serve as a genomic index of sexual selection? An assessment across space and time in a genus of lekking birds

Understanding the role of sexual selection in shaping evolutionary trajectories is a key goal of biology, and thus developing a genomic measure of sexual selection strength is desirable. In systems with ZW sex determination, the ratio of nucleotide diversity ({pi}) on the male-biased Z chromosome to that on the autosomes (the Z:A ratio) is expected to decline as male effective population size decreases under strong sexual selection, offering one such measure. However, non-equilibrium processes other than sexual selection (e.g., hybridization, changes in population size) can influence levels of Z-linked diversity relative to the rest of the genome, complicating interpretation of this metric and necessitating a systematic evaluation of how Z:A ratios vary across known demographic and selective circumstances. We leveraged longitudinal sampling over a [~]25-year period in Manacus manakin populations in western Panama, spanning a mainland transect (including M. candei, M. vitellinus, and their hybrid zone) and insular populations of the Bocas del Toro Archipelago. On the mainland, Z:A ratios were temporally stable within populations, but varied across populations: (1) Z:A ratios were lower in M. vitellinus than M. candei, likely due to stronger sexual selection in the former; and (2) Z:A ratios increased at the hybrid zone center, likely due to fast-Z effects in parentals inflating Z:A ratios in recent hybrids. Island populations exhibited significantly lower Z:A ratios than mainland populations, consistent with theoretical expectations of Z:A reductions following population contractions as the islands became isolated. Insular Z:A ratios increased with proximity to other landmasses, suggesting gene flow mitigates these effects in this system. While the Z:A ratio behaved predictably in relation to known non-equilibrium processes, our results demonstrate the potentially strong effects of demographic history and admixture on Z-linked diversity, which should be considered in studies aiming to use the Z:A ratio as a measure of sexual selection.

evolutionary biology↗

bioRxiv2026

Retention of a female-specific growth hormone receptor gene correlates with reverse sexual size dimorphism in birds

In bird species, larger males are the most common, followed by equal-sized sexes; larger females are rarest. Although multiple forces have been proposed to select for larger female body size, the molecular mechanisms determining this trait remain uncharacterized. The avian gene for growth hormone receptor (GHR) on the Z chromosome is a known factor in sex-specific development. Male birds (ZZ) have two copies of this gene, while females (ZW) typically have one. In addition to the Z copy of GHR found in all birds, we identified a second copy of GHR, documenting its presence or absence across the avian phylogeny by searching over a thousand genomes. This copy was solely found in females. When this second copy can be assigned to a chromosome, it is always located on the W. We infer that this second copy is a gametolog that was present in the common ancestor of extant birds, but has been lost from most lineages. GHR-W has notably been retained in hawks, eagles, vultures (Accipitriformes) and owls (Strigiformes). These groups display larger female size, making GHR-W an intriguing potential contributor to reverse sexual dimorphism. In these lineages, GHR-W retains intact gene structure, despite W-chromosome degradation that leads to loss of this gene from most birds. Analysis of published RNA-seq data demonstrates that GHR-W is expressed in accipitriform fibroblasts. Using available sex-specific mass data and correcting for phylogenetic structure, we report a robust correlation between retention of GHR-W and reverse sexual size dimorphism across avian clades.

evolutionary biology↗

bioRxiv2024

Ecological drivers of CRISPR immune systems

1CRISPR-Cas is the only known adaptive immune system of prokaryotes. It is a powerful defense system against mobile genetic elements such as bacteriophages. While CRISPR-Cas systems can be found throughout the prokaryotic tree of life, they are distributed unevenly across taxa and environments. Since adaptive immunity is more useful in environments where pathogens persist or reoccur, the density and/or diversity of the host/pathogen community may drive the uneven distribution of CRISPR system. We directly tested hypotheses connecting CRISPR incidence with prokaryotic density/diversity by analyzing 16S rRNA and metagenomic data from publicly available environmental sequencing projects. In terms of density, we found that CRISPR systems are significantly favored in lower abundance (less dense) taxa and disfavored in higher abundance taxa, at least in marine environments. When we extended this work to compare taxonomic diversity between samples, we found CRISPR system incidence strongly correlated with diversity in human oral environments. Together, these observations confirm that, at least in certain types of environments, the prokaryotic ecological context indeed plays a key role in selecting for CRISPR immunity. 2 ImportanceMicrobes must constantly defend themselves against viral pathogens, and a large proportion of prokaryotes do so using the highly effective CRISPR-Cas adaptive immune system. However, many prokaryotes do not. We investigated the ecological factors behind this uneven distribution of CRISPR-Cas immune systems in natural microbial populations. We found strong patterns linking CRISPR-Cas systems to prokaryotic density within ocean environments and to prokaryotic diversity within human oral environments. Our study validates previous within-lab experimental results that suggested these factors might be important and confirms that local environment and ecological context interact to select for CRISPR immunity.

microbiology↗

bioRxiv2022

Evolution of the Growth Hormone Gene Duplication in Passerine Birds

Birds of the order Passeriformes represent the most speciose radiation of land vertebrates, yet the cause or causes of their elevated species richness have not been satisfactorily explained. One potential key adaptation is their sole lineage-specific gene, a duplicate copy of growth hormone (GH), present in all major lineages of passerines, but in no other group of birds. Growth hormone genes plausibly influence extreme life history traits that passerines exhibit, including the shortest embryo-to-fledging developmental period of any avian order. To unravel the implications of this GH duplication, we investigated the molecular evolution of the ancestral avian GH gene (GH or GH1) and the novel passerine GH paralog (GH2), using 497 gene sequences extracted from 342 genomes. Passerine GH1 and GH2 are reciprocally monophyletic, consistent with a single duplication event from a microchromosome onto a macrochromosome in a common ancestor of extant passerines. Additional chromosomal rearrangements have changed the syntenic and potential regulatory context of these genes. Both passerine GH1 and GH2 paralogs display substantially higher rates of nonsynonymous codon change than non-passerine avian GH, suggesting positive selection following duplication. A site involved in signal peptide cleavage is under selection in both paralogs. Other sites under positive selection differ between the two paralogs, but many are clustered in one region of a 3D model of the protein. Both paralogs retain key functional features and are actively but differentially expressed in two major passerine suborders. These phenomena suggest that growth hormone genes may be evolving novel adaptive roles in passerine birds.

molecular biology↗

bioRxiv2021

Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination

Understanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze data from two human studies that follow CD8 T cell responses to the yellow fever vaccine (YFV-17D). Models were first fit to the frequency and division rates of YFV-specific memory CD8 T cells 42 days to 1 year post-vaccination. A different dataset, on the loss of YFV-specific CD8 T cells over three decades, was used to assess out of sample predictions of our models. The commonly used exponential and bi-exponential decline models performed relatively poorly. Models with the cell loss following a power law (exactly or approximately) were most predictive. Notably, using only the first year of data, these models accurately predicted T cell frequencies up to 30 years post-vaccination. Our analyses suggest that division rates of these cells drop and plateau at a low level (0.001 per day, ~double estimates for naive T cells) within one year following vaccination, whereas death rates continue to decline for much longer. Our results show that power laws can be predictive for T cell memory, a finding that may be useful for vaccine evaluation and epidemiological modeling. Moreover, since power laws asymptotically decline more slowly than any exponential decline, our results help explain the longevity of immune memory phenomenologically. Author summaryImmunological memory, generated in response to infection or vaccination, may provide complete or partial protection from antigenically similar infections for the lifetime. Memory CD8 T cells are important players in protection from secondary viral infections but quantitative understanding of their dynamics in humans is limited. We analyze data from two studies where immunization with the yellow fever virus vaccine (YFV-17D) generates a mild acute infection and long-term memory. We find that: (i) the division rate of YFV-17D-specific CD8 T cells drops and stabilizes at ~ 0.1% per day during the first year following vaccination whereas the death rate declines more gradually, and (ii) the number of these cells declines approximately in accordance with a power law ({propto}time-0.82) for at least several decades following vaccination.

immunology↗

bioRxiv2019

Potential link between selection for high GC content and repair of double strand breaks in prokaryotic genomes

Genomic GC content varies widely among microbes for reasons unknown. While mutation bias partially explains this variation, prokaryotes near-universally have a higher GC content than predicted solely by this bias. Debate surrounds the relative importance of the remaining explanations of selection versus biased gene conversion favoring GC alleles. Some environments (e.g. soils) are associated with a high genomic GC content of their inhabitants, which implies that this content may be a selective adaptation to particular habitats. Here, we report a novel association between the presence of the non-homologous end joining DNA doublestrand break repair pathway and GC content; this observation suggests that high GC content may be an adaptation to facilitate repair of double strand breaks when homologous recombination is not possible. We discuss potential mechanisms accounting for the observed association, and provide preliminary evidence that sites experiencing higher rates of doublestrand breaks are under selection for increased GC content relative to the genomic background.

microbiology↗