Scientists are sequencing the world’s largest pangenome to help unlock the genetic secrets behind the finer silk

Phenotypic diversity in silkworms. Credit: BGI Genomics

BGI Genomics, in collaboration with Southwestern University, the State Core Laboratory for Silkworm Genome Biology, and other partners, has created a high-resolution pangenome database representing nearly the entire genomic composition of the silkworm.

This research paper, which provides genetic insights into artificial selection (mating and breeding) and ecological adaptation, was published on September 24. Nature Connections.

Previously, there were not many sites associated with traits due to the scarcity of wild silkworms and the technical limitations of past studies. This is the first study to digitize the silkworm gene pool and create a ‘digital silkworm’, greatly facilitating functional genomics studies, promoting precision breeding and thereby enabling additional silk utilization.

The team deep-sequencing 1,078 silkworms (B. mori, including 205 native strains, 194 improved cultivars and 632 genetic stocks, and 47 wild silkworms, B. mandarina) collected the long-read genomes in 545 of these samples, generating T55.57. from genomic data.

This pangenome database contains the most comprehensive information on domestic and wild silkworm genomes and is the largest long-read pangenome in the world for plants and animals to date. At the same time, in-depth research on various genetic variations, population structure, artificial selection and ecological adaptation and economic characteristics of silkworms has been conducted and fruitful results have been obtained.

Scientists have sequenced the world's largest pangenome to unlock the genetic secrets behind finer silk

Characterization of structural variation in 545 silkworm genomes. Credit: BGI Genomics

Origin of the domestic silkworm

From the wild mulberry silkworm B. mandarin to the domesticated house silkworm B. mori. It has a history of more than 5,000 years, but the place of its domestication origin has long been an open question due to a lack of strong biological evidence.

The material in this study represents the richest genetic diversity of all the major sericulture regions of the world. The study found that endemic species in the lower and middle Yellow River region of China spread at the base of the house silkworm branch of the evolutionary tree, thus suggesting that the house silkworm originated in this region. Available archaeological evidence, including a half cocoon excavated in Xiyin Village, Xia County, Shanxi Province in 1926, and a stone-carved silkworm pupa excavated in 2019 in Shicun County, Shanxi Province, provide significant support for this conclusion.

Scientists have sequenced the world's largest pangenome to unlock the genetic secrets behind finer silk

Geographic distribution and phylogenetic tree of the silkworm. Credit: BGI Genomics

Opening the bottleneck in sericulture

The traditional breeding of silkworms has a long and unique history, but has been at a standstill since the 1990s. Systematic analysis of the genetic basis of domestication and improvement of selection are essential to solve the outstanding problems in sericulture. The team identified 468 genes associated with domestication and 198 genes associated with improvement, of which 264 and 185 were newly identified, respectively. These genes will be important candidate targets for silkworm molecular improvement.

At the same time, it was found that Chinese and Japanese beneficial species shared less than 3% of the breeding sites. This not only reveals the relatively independent reproductive histories of the Chinese and Japanese silkworms, but also explains why this shared genetic base provides such hybrid advantages for both species. This result provides new ideas for future silkworm breeding.

Economic characteristics of sericulture

Silk yield and quality have long been considered as the main economic criteria for artificial selection of silkworms. However, to date, little is known about how genes and loci control these quantitative traits. The pangenome is arguably the “closest bridge” between phenotypes, especially complex traits.

Scientists have sequenced the world's largest pangenome to unlock the genetic secrets behind finer silk

Silkworm domestication and breeding. Credit: BGI Genomics

An example is the regulation of silk production by the cell cycle-associated transcription factor BmE2F1, revealed through selection signaling and structural change. CRISPR-cas9-mediated knockout of BmE2F1 reduced silk gland cell number by 7.68% and silk yield by 22%. Conversely, transgenic overexpression of BmE2F1 increases silk gland cell number by 23% and silk yield by 16%.

Fine silk has unique applications and higher economic value, but the genetic basis of fiber fineness was previously unknown. Analysis of rare variants in the genomes of fine cultivars led to the identification of a β-GlcNAcase and CRISPR-cas9-mediated knockout of BmChit β-GlcNAcase, a gene that controls silk fineness, which was significantly detectable in fine cultivars, which resulted in increased production of native silk or silk produced by silk. resulted in coarse silk fineness. . This suggests that this gene plays a key role in determining silk fineness.

Scientists have sequenced the world's largest pangenome to unlock the genetic secrets behind finer silk

Genetic basis of silkworm economic traits. Credit: BGI Genomics

Adaptive features of sericulture

Diapause is a common ecological adaptation in insects that allows insects to survive despite adverse environmental conditions. Although the diapause hormone was first identified in the silkworm in 1957, little is known about the embryonic diapause gene. In this study, BmTret1-like gene was shown to be an important determinant of post-embryonic dormancy based on analysis of silkworm pnd strain and genomic structural variation and functional validation by gene editing. This is the first time that a post-embryonic determinant gene has been identified in an insect.

This study reveals the complete pan-genome of the silkworm to reveal insights into artificial selection and ecological adaptation. “With a comprehensive sample and database combined with a variety of experiments to identify genes for potential future research, we hope to accelerate the silkworm molecular design breeding process,” said co-author and BGI Genomics Senior Scientist Shuaishuai Tai.

A genetic study of the silkworm is helping to unravel its long history of domestication

Xiaoling Tong et al., High-resolution silkworm pan-genome provides genetic insights into artificial selection and ecological adaptation, Nature Connections (2022). DOI: 10.1038/s41467-022-33366-x

Provided by BGI Genomics

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