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Next Regeneration Sequencing for Reference Genomes RESEARCH HIGHLIGHTS Nature Reviews Genetics | Published online 14 Feb 2018; doi:10.1038/nrg.2018.5 John Cancalosi/naturepl.com/Alamy John occurred at the ends of contigs and caused breaks in the assembly, so they are likely to remain a hurdle that limits contig lengths even for long-read genome projects. One of the main values of these reference genomes is as a resource to facilitate further investigation into the genomic underpinnings of regener- ation phenomena. For example, one GENOMICS strategy involves comparing gene and transcript repertoires between species with and without these capabilities to Next regeneration sequencing identify putative regeneration genes, and then designing targeted reagents for reference genomes (such as RNA interference or CRISPR tools) to test the functional Various species have remarkable genomes are substantially more consequences of perturbation. abilities to regenerate body parts or complete than previous draft genomes As one intriguing example, entire organisms after injury, but a for these species. Moreover, the 32 Gb Nowoshilow et al. examined species- the 32 Gb comprehensive understanding of the axolotl genome is the largest genome restricted transcripts in the limb blas- axolotl genome molecular basis of regeneration mech- assembled to date, and is 29-fold tema (from where axolotl limbs are anisms will require detailed genomic more contiguous than the next-largest regenerated) and identified a potential is the largest resources. Two new studies report current genome assembly, the 22 Gb broad role for Ly6-family cell- genome high-quality reference genomes for loblolly pine. surface proteins in regeneration. assembled two classic regeneration model organ- Despite being tenfold larger than Other noteworthy biological infer- to date isms with contrasting genome sizes: the human genome, the axolotl ences from the genomes and tran- the axolotl salamander Ambystoma genome has comparable numbers of scriptomes were that axolotls have mexicanum and the planarium genes to other vertebrates, but with lost the developmental gene Pax3, but flatworm Schmidtea mediterranea. larger intron sizes and intergenic the authors showed using gene editing Both studies centred on long- distances, resulting in the overall large that Pax7 has evolved to carry out the read sequencing using the Pacific genome size. Interestingly, key devel- functions of both Pax3 and Pax7, and Biosciences single-molecule real-time opmental genes show more modest Grohme et al. demonstrated that pla- (SMRT) sequencing platform. The intron expansion (6–11-fold relative narians have lost the spindle assembly multi-kilobase reads enable various to human, mouse and frog) than checkpoint genes MAD1 and MAD2, repetitive tracts to be spanned, which non-developmental genes (13–25- which are almost universally essential minimizes assembly breaks and fold), indicating that developmental in other species; checkpoint functions increases assembly completeness genes are under size constraint, per- were instead provided by the ROD– relative to short-read sequences. To haps to retain tight regulatory control ZW10–ZWILCH (RZZ) complex. facilitate the bioinformatic assembly of their expression. It will be fascinating to see what of repeat-rich long reads into contigs, Although the assembled planarian further functional insights into the teams also devised a new de novo genome is more modest in size at regeneration and development can assembler called MARVEL. 782 Mb, both genomes were domi- be gained from these new genomic The assembled contigs were nated by repetitive DNA and showed resources, including testing putative then ordered onto larger scaffolds clear evidence of recent expansions regenerative roles for species- derived from long-range mapping of long terminal repeat (LTR) retro­ restricted genes and repetitive information from Bionano Saphyr elements. The planarian genome elements. Darren J. Burgess hybridization-based optical map- contained a new class of particularly ping (for the axolotl genome by long >30 kb elements, which is a ORIGINAL ARTICLES Nowoshilow, S. et al. The Nowoshilow et al.) or from Chicago/ likely reason why previous short- axolotl genome and the evolution of key tissue formation regulators. Nature https://doi.org/ HiRise sequencing of 3D-proximal read approaches failed to generate a 10.1038/nature25458 (2018) | Grohme, M. A. et al. locus pairs (for the planarian genome high-quality reference genome. Even The genome of Schmidtea mediterranea and the by Grohme et al.). From this multilay- for these latest long-read reference evolution of core cellular mechanisms. Nature https://doi.org/10.1038/nature25473 (2018) ered pipeline, the resultant reference genomes, LTR elements frequently NATURE REVIEWS | GENETICS www.nature.com/nrg ©2018 Mac millan Publishers Li mited, part of Spri nger Nature. All ri ghts reserved. .
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