Biology subjects

Seidel, H. S.

Publications and source records attributed to Seidel, H. S..

6 recordsLinked to original sources

bioRxiv2023

A frameshift variant in the melanophilin gene is associated with loss of pigment from shed skin in ball pythons (Python regius)

Melanophilin is a myosin adaptor required for transporting the pigment melanin within cells. Loss of melanophilin in fish, birds, and mammals causes pigmentation defects, but little is known about the role of melanophilin in non-avian reptiles. Here we show that a frameshift in the melanophilin gene in ball python (P. regius) is associated with loss of pigment from shed skin. This variant is predicted to remove the myosin-binding domain of melanophilin and thereby impair transport of melanin-containing organelles. Our study represents the first description of a melanophilin variant in a non-avian reptile and confirms the role of melanophilin across vertebrates.

genetics↗

bioRxiv2022

Leucism and stripe formation in ball pythons (Python regius) are associated with variants affecting endothelin signaling

Color patterns in non-avian reptiles are beautifully diverse, but little is known about the genetics and development of these patterns. Here we investigated color patterning in pet ball pythons (Python regius), which have been bred to show color phenotypes that differ dramatically from the wildtype form. We report that several color phenotypes in pet animals are associated with putative loss-of-function variants in the gene encoding endothelin receptor EDNRB1: (i) frameshift variants in EDNRB1 are associated with conversion of the normal mottled color pattern to skin that is almost fully white, (ii) missense variants affecting conserved sites of the EDNRB1 protein are associated with dorsal, longitudinal stripes, and (iii) substitutions at EDNRB1 splice donors are associated with subtle changes in patterning compared to wildtype. We propose that these phenotypes are caused by loss of specialized color cells (chromatophores), with loss ranging from severe (fully white) to moderate (dorsal striping) to mild (subtle changes in patterning). Our study is the first to describe variants affecting endothelin signaling in a non-avian reptile and suggests that reductions in endothelin signaling in ball pythons can produce a variety of color phenotypes, depending on the degree of color cell loss.

genetics↗

bioRxiv2021

A community-science approach identifies genetic variants associated with three color morphs in ball pythons (Python regius)

Color morphs in ball pythons (Python regius) provide a unique and largely untapped resource for understanding the genetics of coloration in reptiles. Here we use a community-science approach to investigate the genetics of three color morphs affecting production of the pigment melanin. These morphs--Albino, Lavender Albino, and Ultramel--show a loss of melanin in the skin and eyes, ranging from severe (Albino) to moderate (Lavender Albino) to mild (Ultramel). To identify genetic variants causing each morph, we recruited shed skins of pet ball pythons via social media, extracted DNA from the skins, and searched for putative loss-of-function variants in homologs of genes controlling melanin production in other vertebrates. We report that the Albino morph is associated with missense and non-coding variants in the gene TYR. The Lavender Albino morph is associated with a deletion in the gene OCA2. The Ultramel morph is associated with a missense variant and a putative deletion in the gene TYRP1. Our study is one of the first to identify genetic variants associated with color morphs in ball pythons and shows that pet samples recruited from the community can provide a resource for genetic studies in this species.

genetics↗

bioRxiv2020

Selfing is the safest sex for Caenorhabditis tropicalis

Mating systems have profound effects on genetic diversity and compatibility. The convergent evolution of self-fertilization in three Caenorhabditis species provides a powerful lens to examine causes and consequences of mating system transitions. Among the selfers, C. tropicalis is the least genetically diverse and most afflicted by outbreeding depression. We generated a chromosomal-scale genome for C. tropicalis and surveyed global diversity. Population structure is very strong, and islands of extreme divergence punctuate a genomic background that is highly homogeneous around the globe. Outbreeding depression in the laboratory is caused largely by multiple gene drive elements, genetically consistent with maternal toxin/zygotic antidote systems. Driver loci harbor novel and duplicated genes, and their activity is modified by mito-nuclear background. Segregating drivers dramatically reduce fitness, and simulations show that selfing limits their spread. Frequent selfing in C. tropicalis may therefore be a strategy to avoid drive-mediated outbreeding depression.

evolutionary biology↗

bioRxiv2018

C. elegans germ cells divide and differentiate along a folded epithelium

Knowing how stem cells and their progeny are positioned within their tissues is essential for understanding their regulation. One paradigm for stem cell regulation is the C. elegans germline, which is maintained by a pool of germline stem cells in the distal gonad, in a region known as the progenitor zone. The C. elegans germline is widely used as a stem cell model, but the cellular architecture of the progenitor zone has been unclear. Here we characterize this architecture by creating virtual 3D models of the progenitor zone in both sexes. We show that the progenitor zone in adult hermaphrodites is essentially a folded epithelium. The progenitor zone in males is not folded. Analysis of germ cell division shows that daughter cells are born side-by-side along the surface of the epithelium. Analysis of a key regulator driving differentiation, GLD-1, shows that germ cells in hermaphrodites differentiate along the path of the folded epithelium, with previously described \"steps\" in GLD-1 expression corresponding to germline folds. Our study provides a three-dimensional view of how C. elegans germ cells progress from stem cell to overt differentiation, with critical implications for regulators driving this transition.

developmental biology↗

bioRxiv2017

Natural variation in a single amino acid underlies cellular responses to topoisomerase II poisons

Many medications, including chemotherapeutics, are differentially effective from one patient to the next. Understanding the causes of these population-wide differences is a critical step towards the development of personalized treatments and improvements to existing medications. Here, we investigate natural differences in sensitivity to anti-neoplastic drugs that target topoisomerase II, using the model organism Caenorhabditis elegans. We show that wild isolates of C. elegans vary in their sensitivity to these drugs, and we use an unbiased statistical and molecular genetics approach to demonstrate that this variation is explained by a methionine-to-glutamine substitution in topoisomerase II (TOP-2). The presence of a non-polar methionine at this residue increases hydrophobic interactions between TOP-2 and the poison etoposide, as compared to a polar glutamine. We hypothesize that this stabilizing interaction results in increased genomic instability in strains that contain a methionine residue. The residue affected by this substitution is conserved from yeast to humans and is one of the few differences between the two human topoisomerase II isoforms (methionine in hTOPII and glutamine in hTOPII{beta}). We go on to show that this substitution influences binding and cytotoxicity of etoposide and two additional topoisomerase II poisons in human cell lines. These results explain why hTOPII and hTOPII{beta} are differentially affected by various poisons and demonstrate the utility of C. elegans in understanding the genetics of drug responses.

genetics↗