Hybrid de novo genome assembly and centromere characterization of the gray mouse lemur (Microcebus murinus).

TitleHybrid de novo genome assembly and centromere characterization of the gray mouse lemur (Microcebus murinus).
Publication TypeJournal Article
Year of Publication2017
AuthorsLarsen, PA, Harris, RA, Liu, Y, Murali, SC, C Campbell, R, Brown, AD, Sullivan, BA, Shelton, J, Brown, SJ, Raveendran, M, Dudchenko, O, Machol, I, Durand, NC, Shamim, MS, Aiden, ELieberman, Muzny, DM, Gibbs, RA, Yoder, AD, Rogers, J, Worley, KC
JournalBMC Biol
Date Published2017 Nov 16
KeywordsAnimals, Centromere, Cheirogaleidae, Computational Biology, Female, Genome, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA

BACKGROUND: The de novo assembly of repeat-rich mammalian genomes using only high-throughput short read sequencing data typically results in highly fragmented genome assemblies that limit downstream applications. Here, we present an iterative approach to hybrid de novo genome assembly that incorporates datasets stemming from multiple genomic technologies and methods. We used this approach to improve the gray mouse lemur (Microcebus murinus) genome from early draft status to a near chromosome-scale assembly.METHODS: We used a combination of advanced genomic technologies to iteratively resolve conflicts and super-scaffold the M. murinus genome.RESULTS: We improved the M. murinus genome assembly to a scaffold N50 of 93.32 Mb. Whole genome alignments between our primary super-scaffolds and 23 human chromosomes revealed patterns that are congruent with historical comparative cytogenetic data, thus demonstrating the accuracy of our de novo scaffolding approach and allowing assignment of scaffolds to M. murinus chromosomes. Moreover, we utilized our independent datasets to discover and characterize sequences associated with centromeres across the mouse lemur genome. Quality assessment of the final assembly found 96% of mouse lemur canonical transcripts nearly complete, comparable to other published high-quality reference genome assemblies.CONCLUSIONS: We describe a new assembly of the gray mouse lemur (Microcebus murinus) genome with chromosome-scale scaffolds produced using a hybrid bioinformatic and sequencing approach. The approach is cost effective and produces superior results based on metrics of contiguity and completeness. Our results show that emerging genomic technologies can be used in combination to characterize centromeres of non-model species and to produce accurate de novo chromosome-scale genome assemblies of complex mammalian genomes.

Alternate JournalBMC Biol
PubMed ID29145861
PubMed Central IDPMC5689209
Grant ListP20 GM103418 / GM / NIGMS NIH HHS / United States
S10 OD018164 / OD / NIH HHS / United States
R01 GM124041 / GM / NIGMS NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States

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