Large‐scale variation in single nucleotide polymorphism density within the laboratory axolotl (Ambystoma mexicanum)

Abstract

Background: Recent efforts to assemble and analyze the Ambystoma mexicanum genome have dramatically improved the potential to develop molecular tools and pursue genome-wide analyses of genetic variation.Results: To better resolve the distribution and origins of genetic variation with A mexicanum, we compared DNA sequence data for two laboratory A mexicanum and one A tigrinum to identify 702 million high confidence polymorphisms distributed across the 32 Gb genome. While the wild-caught A tigrinum was generally more polymorphic in a genome-wide sense, several multi-megabase regions were identified from A mexicanum genomes that were actually more polymorphic than A tigrinum. Analysis of polymorphism and repeat content reveals that these regions likely originated from the intentional hybridization of A mexicanum and A tigrinum that was used to introduce the albino mutation into laboratory stocks.Conclusions: Our findings show that axolotl genomes are variable with respect to introgressed DNA from a highly polymorphic species. It seems likely that other divergent regions will be discovered with additional sequencing of A mexicanum. This has practical implications for designing molecular probes and suggests a need to study A mexicanum phenotypic variation and genome evolution across the tiger salamander clade.

Evaluation of genetic demultiplexing of single-cell sequencing data from model species

“…The axolotl is an example of the type of organism for which scRNA-seq has enabled cell level study of regeneration and immunology for the first time ( Gerber et al, 2018 ; Leigh et al, 2018 ; Rodgers et al, 2020 ; Lin et al, 2021 ; Lust et al, 2022 ; Ye et al, 2022 ). A genome ( Nowoshilow et al, 2018 ; Smith et al, 2019 ) and SNP variant VCF file ( Timoshevskaya et al, 2021 ) are available for the axolotl, but its large genome provides a distinct challenge when using computational tools. We used in silico pooling for three individually sequenced axolotl single-nuclei RNA-seq datasets ( Fig S5A ) ( Lust et al, 2022 ).…”

Accurate genotype-based demultiplexing of single cell RNA sequencing samples from non-human animals

“…The axolotl is an example of the type of organism for which scRNA-seq has enabled cell level study of regeneration and immunology for the first time (Gerber et al 2018; Lin et al 2021; Leigh et al 2018; Rodgers, Smith, and Voss 2020; Lust et al 2022; Ye et al 2022). Additionally, a genome(Nowoshilow et al 2018; Smith et al 2019) and SNP variant VCF file (Timoshevskaya et al 2021) are available for the axolotl, but its large genome provides a distinct challenge when using computational tools. snRNA-seq data from the brain of three individual axolotl was recently published (Lust et al 2022).…”

“…Additionally, a genome (Nowoshilow et al 2018;Smith et al 2019) and SNP variant VCF file (Timoshevskaya et al 2021) are available for the axolotl, but its large genome provides a distinct challenge when using computational tools. snRNA-seq data from the brain of three individual axolotl was recently published (Lust et al 2022).…”

Salamander models for elucidating mechanisms of developmental biology, evolution, and regeneration: Part one

“…Related to the salamander genome, a new high‐resolution study of the genetic composition of two axolotls in the Ambystoma Genetic Stock Center at the University of Kentucky, performed by Timoshevskaya et al provides the community with >700 million polymorphisms 11 . They also compared the identified loci to orthologous sites in a wild‐caught tiger salamander ( Ambystoma tigrinum ) sample and present evidence that many of the polymorphisms now present in laboratory axolotls may have arisen from crosses between axolotls and tiger salamanders in the stock center when the albino mutant line was established.…”