A chromosome-scale assembly of the axolotl genome

Genome Research, 2019 · DOI: 10.1101/gr.241901.118 · Published: March 1, 2019

Simple Explanation

The axolotl genome, which is about 10 times the size of the human genome, has been a barrier to genetic analysis. This study presents a chromosome-scale assembly of the axolotl genome, covering 27.3 Gb and encompassing 94% of annotated gene models on chromosomal scaffolds. The new assembly allows for resolving genome-wide orthologies between the axolotl and other vertebrates. It also allows for identifying the footprints of historical introgression events and precisely mapping several phenotypes including a large deletion underlying the cardiac mutant. The chromosome-scale assembly will greatly facilitate studies of the axolotl in biological research, enabling a deeper understanding of its unique biological properties, such as regeneration.

Study Duration

Not specified

Participants

48 segregants of a hybrid A. mexicanum/A. tigrinum backcross

Evidence Level

Not specified

Key Findings

1
The study successfully assembled the axolotl genome into 14 chromosomes, covering 27.3 Gb and encompassing 94% of annotated gene models.
2
The assembly revealed broad-scale conservation of genome structure across vertebrates and identified previously unreported fusion events in the common ancestral lineage of amphibians.
3
The assembly facilitated the localization of the mutation underlying the cardiac mutant to a specific deletion within the tnnt2 gene on Chromosome 13.

Research Summary

This study presents a cost-effective approach to scaffolding the large axolotl genome and validates the resulting assembly using FISH and analysis of synteny conservation across vertebrates. The utility of this assembly is demonstrated by resolving patterns of genome-wide SNP variation that reveal the footprints of a historical introgression event and resolve the genetic underpinnings of the classical mutant phenotype cardiac. The work sets the stage for routine analyses at this scale, including SNP-based approaches and other analyses that involve large-scale signatures such as epigenetic remodeling events and promotor–enhancer interactions.

Practical Implications

Improved Understanding of Regeneration

The chromosome-scale assembly allows for studying long-range interactions that are critical for regulating transcription, which is likely critical to understanding the gene-regulatory basis of tissue regeneration.

Facilitated Genetic Analyses

The assembly enables more accurate and precise design of gene-editing tools to empower reverse genetic experiments, accelerating gene discovery and mutant analysis.

Insights into Genome Evolution

The comparative synteny analyses provide insights into genome structure and fusion/fission events that underlie differences in chromosome number and content between taxa.

Study Limitations

1
The initial attempts to develop a chromosome-scale assembly using a proximity ligation approach (DoveTail) revealed limitations of the approach and yielded few useful results.
2
The mapping panel was generated by backcrossing F1 hybrid A. mexicanum/A. tigrinum to A. mexicanum.
3
The study used low-coverage sequence data from 48 segregants.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine