Improving Genome Assemblies and Annotations for Nonhuman Primates

Abstract

The study of nonhuman primates (NHP) is key to understanding human evolution, in addition to being an important model for biomedical research. NHPs are especially important for translational medicine. There are now exciting opportunities to greatly increase the utility of these models by incorporating Next Generation (NextGen) sequencing into study design. Unfortunately, the draft status of nonhuman genomes greatly constrains what can currently be accomplished with available technology. Although all genomes contain errors, draft assemblies and annotations contain so many mistakes that they make currently available nonhuman primate genomes misleading to investigators conducting evolutionary studies; and these genomes are of insufficient quality to serve as references for NextGen studies. Fortunately, NextGen sequencing can be used in the production of greatly improved genomes. Existing Sanger sequences can be supplemented with NextGen whole genome, and exomic genomic sequences to create new, more complete and correct assemblies. Additional physical mapping, and an incorporation of information about gene structure, can be used to improve assignment of scaffolds to chromosomes. In addition, mRNA-sequence data can be used to economically acquire transcriptome information, which can be used for annotation. Some highly polymorphic and complex regions, for example MHC class I and immunoglobulin loci, will require extra effort to properly assemble and annotate. However, for the vast majority of genes, a modest investment in money, and a somewhat greater investment in time, can greatly improve assemblies and annotations sufficient to produce true, reference grade nonhuman primate genomes. Such resources can reasonably be expected to transform nonhuman primate research.

The Juicebox Assembly Tools module facilitatesde novoassembly of mammalian genomes with chromosome-length scaffolds for under $1000

“…Scaffolds can contain errors in contig order (a 'translocation') or orientation (an 'inversion'). Examples of such errors can be found in the best available reference genomes for many species (Robert B. Norgren 2013;Shearer et al 2014;Tang et al 2014;Chen et al 2015;Davey et al 2016;Utsunomiya et al 2016;Schneider et al 2017;Korlach et al 2017). Consequently, inexpensive methods for identifying and correcting assembly errors are crucial for the generation of accurate assemblies (Salzberg and Yorke 2005;Phillippy, Schatz, and Pop 2008;Gnerre et al 2009;Tsai, Otto, and Berriman 2010;Salzberg et al 2012;Hunt et al 2013;Gurevich et al 2013;Bradnam et al 2013;Simão et al 2015;Fierst 2015;Muggli et al 2015;Yuan et al 2017;Harewood et al 2017).…”

The devil is in the details: Transposable element analysis of the Tasmanian devil genome

“…Even the genomes of primates are often inadequately assembled, despite being closely related to humans. 37 Thus, reliance on in silico data for investigation of active LINEs, ERVs or even SINE activity in a genome is problematic and makes in-vitro experimental methods necessary to verify new and unexpected findings.…”

Evolutionary History and Genetic Variation of Macaca mulatta and Macaca fascicularis

“…Complete reference genomes are now available for the chimpanzee, bonobo, gorilla, orangutan, rhesus macaque, and cynomolgus macaque, and those for the gibbon, sooty mangabey, vervet (African Green) monkey, baboon (Papio anubis), pigtail macaque, sifaka, marmoset, and mouse lemur are now in progress and will be completed soon [40]. The ever-increasing number of reference genomes of species of NHPs becoming available should increase the power of comparative studies to identify adaptive changes through the evolution of primate species responsible for observed phenotypic differences between/among species, particularly those that make humans distinct.…”