Biology subjects

Voss, S. R.

Publications and source records attributed to Voss, S. R..

5 recordsLinked to original sources

bioRxiv2026

Dissecting functional elements in giant genomes using the first generation of high quality salamander assemblies

Salamanders are an enduring and historically significant group that helped originate multiple scientific fields of study, including regeneration, cytogenetics, experimental embryology, cloning, evolutionary developmental biology and evolution of extreme genome size. We generated a high-quality, single haplotype assembly for the 32 Gb axolotl (Ambystoma mexicanum) genome using an F1 hybrid between axolotl and a divergent relative the tiger salamander (A. tigrinum). Using multi-genome alignments to other salamanders that meet VGP metrics, we leveraged strong conservation of karyotypic structure to identify >523,000 highly conserved non-coding elements within massively expanded intronic and intergenic regions, the vast majority of which are unique to the salamander lineage. Orthogonal measures of chromatin state and enhancer activity confirmed that many conserved elements correspond to cis-regulatory sequences and identified several thousand that are utilized during regeneration. The conserved elements identified here will enable robust functional genomic analyses of tissue regeneration and other traits that uniquely empower salamander models in biological research.

genomics↗

bioRxiv2024

Retinoic acid breakdown is required for proximodistal positional identity during amphibian limb regeneration

Regenerating limbs retain their proximodistal (PD) positional identity following amputation. This positional identity is genetically encoded by PD patterning genes that instruct blastema cells to regenerate the appropriate PD limb segment. Retinoic acid (RA) is known to specify proximal limb identity, but how RA signaling levels are established in the blastema is unknown. Here, we show that RA breakdown via CYP26B1 is essential for determining RA signaling levels within blastemas. CYP26B1 inhibition molecularly reprograms distal blastemas into a more proximal identity, phenocopying the effects of administering excess RA. We identify Shox as an RA-responsive gene that is differentially expressed between proximally and distally amputated limbs. Ablation of Shox results in shortened limbs with proximal skeletal elements that fail to initiate endochondral ossification. These results suggest that PD positional identity is determined by RA degradation and RA-responsive genes that regulate PD skeletal element formation during limb regeneration.

developmental biology↗

bioRxiv2024

Do organisms need an impact factor? Citations of key biological resources including model organisms reveal usage patterns and impact.

Research resources like transgenic animals and antibodies are the workhorses of biomedicine, enabling investigators to relatively easily study specific disease conditions. As key biological resources, transgenic animals and antibodies are often validated, maintained, and distributed from university based stock centers. As these centers heavily rely largely on grant funding, it is critical that they are cited by investigators so that usage can be tracked. However, unlike systems for tracking the impact of papers, the conventions and systems for tracking key resource usage and impact lag behind. Previous studies have shown that about 50% of the resources are not findable, making the studies they are supporting irreproducible, but also makes tracking resources difficult. The RRID project is filling this gap by working with journals and resource providers to improve citation practices and to track the usage of these key resources. Here, we reviewed 10 years of citation practices for five university based stock centers, characterizing each reference into two broad categories: findable (authors could use the RRID, stock number, or full name) and not findable (authors could use a nickname or a common name that is not unique to the resource). The data revealed that when stock centers asked their communities to cite resources by RRID, in addition to helping stock centers more easily track resource usage by increasing the number of RRID papers, authors shifted from citing resources predominantly by nickname ([~]50% of the time) to citing them by one of the findable categories ([~]85%) in a matter of several years. In the case of one stock center, the MMRRC, the improvement in findability is also associated with improvements in the adherence to NIH rigor criteria, as determined by a significant increase in the Rigor and Transparency Index for studies using MMRRC mice. From this data, it was not possible to determine whether outreach to authors or changes to stock center websites drove better citation practices, but findability of research resources and rigor adherence was improved.

bioinformatics↗

bioRxiv2018

A Chromosome-Scale Assembly of the Enormous (32 Gb) Axolotl Genome

The axolotl (Ambystoma mexicanum) provides critical models for studying regeneration, evolution and development. However, its large genome (~32 gigabases) presents a formidable barrier to genetic analyses. Recent efforts have yielded genome assemblies consisting of thousands of unordered scaffolds that resolve gene structures, but do not yet permit large scale analyses of genome structure and function. We adapted an established mapping approach to leverage dense SNP typing information and for the first time assemble the axolotl genome into 14 chromosomes. Moreover, we used fluorescence in situ hybridization to verify the structure of these 14 scaffolds and assign each to its corresponding physical chromosome. This new assembly covers 27.3 gigabases and encompasses 94% of annotated gene models on chromosomal scaffolds. We show the assemblys utility by resolving genome-wide orthologies between the axolotl and other vertebrates, identifying the footprints of historical introgression events that occurred during the development of axolotl genetic stocks, and precisely mapping several phenotypes including a large deletion underlying the cardiac mutant. This chromosome-scale assembly will greatly facilitate studies of the axolotl in biological research.

genomics↗

bioRxiv2018

Miniscule differences between the sex chromosomes in the giant genome of a salamander, Ambystoma mexicanum

In the Mexican axolotl (Ambystoma mexicanum) sex is known to be determined by a single Mendelian factor, yet the sex chromosomes of this model salamander do not exhibit morphological differentiation that is typical of many vertebrate taxa that possess a single sex-determining locus. Differentiated sex chromosomes are thought to evolve rapidly in the context of a Mendelian sex-determining gene and, therefore, undifferentiated chromosomes provide an exceptional opportunity to reconstruct early events in sex chromosome evolution. Whole chromosome sequencing, whole genome resequencing (48 individuals from a backcross of axolotl and tiger salamander) and in situ hybridization were used to identify a homomorphic chromosome that carries an A. mexicanum sex determining factor and identify sequences that are present only on the W chromosome. Altogether, these sequences cover ~300 kb, or roughly 1/100,000th of the ~32 Gb genome. Notably, these W-specific sequences also contain a recently duplicated copy of the ATRX gene: a known component of mammalian sex-determining pathways. This gene (designated ATRW) is one of the few functional (non-repetitive) genes in the chromosomal segment and maps to the tip of chromosome 9 near the marker E24C3, which was previously found to be linked to the sex-determining locus. These analyses provide highly predictive markers for diagnosing sex in A. mexicanum and identify ATRW as a strong candidate for the primary sex determining locus or alternately a strong candidate for a recently acquired, sexually antagonistic gene.\n\nAUTHOR SUMMARYSex chromosomes are thought to follow fairly stereotypical evolutionary trajectories that result in differentiation of sex-specific chromosomes. In the salamander A. mexicanum (the axolotl), sex is determined by a single Mendelian locus, yet the sex chromosomes are essentially undifferentiated, suggesting that these sex chromosomes have recently acquired a sex locus and are in the early stages of differentiating. Although Mendelian sex determination was first reported for the axolotl more than 70 years ago, no sex-specific sequences have been identified for this important model species. Here, we apply new technologies and approaches to identify and validate a tiny region of female-specific DNA within the gigantic genome of the axolotl (1/100,000th of the genome). This region contains a limited number of genes, including a duplicate copy of the ATRX gene which, has been previously shown to contribute to mammalian sex determination. Our analyses suggest that this gene, which we refer to as ATRW, evolved from a recent duplication and presents a strong candidate for the primary sex determining factor of the axolotl, or alternately a recently evolved sexually antagonistic gene.

evolutionary biology↗