Biology subjects

Davidson, W. S.

Publications and source records attributed to Davidson, W. S..

6 recordsLinked to original sources

bioRxiv2024

Host lipids regulate multicellular behavior of a predator of a human pathogen

As symbionts of animals, microbial eukaryotes benefit and harm their hosts in myriad ways. A model microeukaryote (Capsaspora owczarzaki) is a symbiont of Biomphalaria glabrata snails and may prevent transmission of parasitic schistosomes from snails to humans. However, it is unclear which host factors determine Capsasporas ability to colonize snails. Here, we discovered that Capsaspora forms multicellular aggregates when exposed to snail hemolymph. We identified a molecular cue for aggregation: a hemolymph-derived phosphatidylcholine, which becomes elevated in schistosome-infected snails. Therefore, Capsaspora aggregation may be a response to the physiological state of its host, and it may determine its ability to colonize snails and exclude parasitic schistosomes. Furthermore, Capsaspora is an evolutionary model organism whose aggregation may be ancestral to animals. This discovery, that a prevalent lipid induces Capsaspora multicellularity, suggests that this aggregation phenotype may be ancient. Additionally, the specific lipid will be a useful tool for further aggregation studies.

biochemistry↗

bioRxiv2022

Chemical factors induce aggregative multicellularity in a close unicellular relative of animals

Regulated cellular aggregation is an essential process for development and healing in many animal tissues. In some animals and a few distantly related unicellular species, cellular aggregation is regulated by diffusible chemical cues. However, it is unclear whether regulated cellular aggregation was part of the life cycles of the first multicellular animals and/or their unicellular ancestors. To fill this gap, we investigated the triggers of cellular aggregation in one of animals closest unicellular living relatives - the filasterean Capsaspora owczarzaki. We discovered that Capsaspora aggregation is induced by chemical cues, as observed in some of the earliest branching animals and other unicellular species. Specifically, we found that calcium ions and lipids present in lipoproteins function together to induce aggregation of viable Capsaspora cells. We also found that this multicellular stage is reversible, as depletion of the cues triggers disaggregation, which can be overcome upon re-induction. Our finding demonstrates that chemically regulated aggregation is important across diverse members of the holozoan clade. Therefore, this phenotype was plausibly integral to the life cycles of the unicellular ancestors of animals.

biochemistry↗

bioRxiv2022

Isolation-by-distance and population-size history inferences from the coho salmon (Oncorhynchus kisutch) genome

Coho salmon (Oncorhynchus kisutch) are a culturally and economically important species that return from multiyear ocean migrations to spawn in rivers that flow to the Northern Pacific Ocean. Southern stocks of coho salmon have significantly declined over the past quarter century, and unfortunately, conservation efforts have not reversed this trend. To assist in stock management and conservation efforts, we generated two chromosome-level genome assemblies and sequenced 24 RNA-seq libraries to better annotate the coho salmon genome assemblies. We also resequenced the genomes of 83 coho salmon across their North American range to identify nucleotide variants, characterize the broad effects of isolation-by-distance using a genome-wide association analysis approach, and understand the demographic histories of these salmon by modeling population size from genome-wide data. We observed that more than 13% of all SNPs were associated with latitude (before multiple test correction), likely an affect of isolation-by-distance. From demographic history modeling, we estimated that the SNP latitudinal gradient likely developed as recently as 8,000 years ago. In addition, we identified four genes each harboring multiple SNPs associated with latitude; all of these SNPs were also predicted to modify the function of the gene. Three of these genes have roles in cell junction maintenance and may be involved in osmoregulation. This signifies that ocean salinity may have been a factor influencing coho salmon recolonization after the last glaciation period - generating the current pattern of variation in these three genes.

genomics↗

bioRxiv2019

4-oxo-2-nonenal Adducts In HDL Are Elevated In Familial Hypercholesterolemia: Identification Of Modified Sites And Functional Consequences

The lipid aldehyde 4-oxo-2-nonenal (ONE) derived from peroxidation of n-6 polyunsaturated fatty acids and generated in parallel to 4-hydroxynonenal (HNE) is a highly reactive protein crosslinker. Crosslinking of proteins in high-density lipoprotein (HDL) by lipid peroxidation products causes HDL dysfunction and contributes to atherogenesis. While HNE is relatively well studied, the relevance of ONE in atherosclerosis and in modifying HDL has not been examined. In the present study, we found a significant increase in ONE-ketoamide (lysine) adducts in HDL derived from patients with familial hypercholesterolemia (FH) (1620 {+/-} 985.4 pmol/mg) compared to healthy controls (664 {+/-} 219.5 pmol/mg). ONE crosslinked apoA-I on HDL at a concentration of >3 mol ONE per 10 mol apoA-I (0.3 eq), which is 100-fold lower than HNE but comparable to the potent protein crosslinker, isolevuglandin. ONE-modified HDL partially inhibited the ability of HDL to protect against LPS-induced TNF and IL-1{beta} mRNA expression in murine macrophages. At 3 eq., ONE dramatically decreased the ability of apoA-I to exchange from HDL, from ~46.5% to only ~18.4% (P<0.001). Surprisingly, ONE-modification of HDL or apoA-I did not alter macrophage cholesterol efflux capacity. LC/MS/MS analysis showed modification of Lys12, Lys23, Lys96, and Lys226 of apoA-I by ONE-ketoamide adducts. Compared to other dicarbonyl scavengers, pentylpyridoxamine (PPM) was most efficacious at blocking ONE-induced protein crosslinking in HDL. Our studies show that ONE HDL adducts are elevated in FH who have severe hypercholesterolemia and atherosclerosis and causes HDL dysfunction. We demonstrate the use of PPM in preferentially scavenging ONE in biological systems.

biochemistry↗

bioRxiv2018

Whole genome linkage disequilibrium and effective population size in a coho salmon (Oncorhynchus kisutch) breeding population

The estimation of linkage disequilibrium between molecular markers within a population is critical when establishing the minimum number of markers required for association studies, genomic selection and for inferring historical events influencing different populations. This work aimed to evaluate the extent and decay of linkage disequilibrium in a coho salmon breeding population using ddRAD genomic markers.\n\nLinkage disequilibrium was estimated between a total of 7,505 SNPs found in 62 individuals (33 dams and 29 sires) from the breeding population. The makers encompass all 30 coho salmon chromosomes and comprise 1,655.19 Mb of the genome. The average density of markers per chromosome ranged from 3.45 to 6.11 per 1 Mbp. The minor allele frequency averaged 0.20 (with a range from 0.08 to 0.50). The overall average linkage disequilibrium among SNPs pairs measured as r2 was 0.054. The Average r2 value decreased with increasing physical distance, with values ranging from 0.37 to 0.054 at distances lower than 1 kb and up to 10 Mb, respectively. An r2 threshold of 0.1 was reached at distance of approximately 1.3 Mb. Chromosomes Okis05, Okis15 and Okis28 showed high levels of linkage disequilibrium (> 0.20 at distances lower than 1 Mb). Average r2 values were lower than 0.1 for all chromosomes at distances greater than 4 Mb. Linkage disequilibrium values suggest that whole genome association and selection studies could be performed using about 75,000 SNPs in aquaculture populations (depending on the trait under investigation). From the identified SNPs, an effective population size of 100 was estimated for the population 10 generation ago, and 1,000, for 139 generations ago.\n\nBased on the extent of r2 decay, we suggest that at least 75,000 SNPs would be necessary for an association mapping study. Over 100,000 SNPs would be necessary for a high power study, in the current coho salmon population.

genomics↗

bioRxiv2016

Functional Analysis of All Salmonid Genomes (FAASG): an international initiative supporting future salmonid research, conservation and aquaculture

We describe an emerging initiative - the Functional Analysis of All Salmonid Genomes (FAASG), which will leverage the extensive trait diversity that has evolved since a whole genome duplication event in the salmonid ancestor, to develop an integrative understanding of the functional genomic basis of phenotypic variation. The outcomes of FAASG will have diverse applications, ranging from improved understanding of genome evolution, through to improving the efficiency and sustainability of aquaculture production, supporting the future of fundamental and applied research in an iconic fish lineage of major societal importance.

genomics↗