Genomic structural variation contributes to evolved changes in gene expression in high-altitude Tibetan sheep.

Tibetan sheep were introduced to the Qinghai Tibet plateau roughly 3,000 B.P., making this species a good model for investigating genetic mechanisms of high-altitude adaptation over a relatively short timescale. Here, we characterize genomic structural variants (SVs) that distinguish Tibetan sheep from closely related, low-altitude Hu sheep, and we examine associated changes in tissue-specific gene expression. We document differentiation between the two sheep breeds in frequencies of SVs associated with genes involved in cardiac function and circulation. In Tibetan sheep, we identified high-frequency SVs in a total of 462 genes, including EPAS1, PAPSS2, and PTPRD. Single-cell RNA-Seq data and luciferase reporter assays revealed that the SVs had cis-acting effects on the expression levels of these three genes in specific tissues and cell types. In Tibetan sheep, we identified a high-frequency chromosomal inversion that exhibited modified chromatin architectures relative to the noninverted allele that predominates in Hu sheep. The inversion harbors several genes with altered expression patterns related to heart protection, brown adipocyte proliferation, angiogenesis, and DNA repair. These findings indicate that SVs represent an important source of genetic variation in gene expression and may have contributed to high-altitude adaptation in Tibetan sheep.

Sympatric speciation of the spiny mouse from Evolution Canyon in Israel substantiated genomically and methylomically.

SignificanceWhether sympatric speciation (SS) is rare or common is still debated. Two populations of the spiny mouse, Acomys cahirinus, from Evolution Canyon I (EC I) in Israel have been depicted earlier as speciating sympatrically by molecular markers and transcriptome. Here, we investigated SS both genomically and methylomically, demonstrating that the opposite populations of spiny mice are sister taxa and split from the common ancestor around 20,000 years ago without an allopatric history. Mate choice, olfactory receptors, and speciation genes contributed to prezygotic/postzygotic reproductive isolation. The two populations showed different methylation patterns, facilitating adaptation to their local environment. They cope with abiotic and biotic stresses, due to high solar interslope radiation differences. We conclude that our new genomic and methylomic data substantiated SS.

Genomic insights into zokors' phylogeny and speciation in China.

The phylogeny and speciation of subterranean zokors in China are unclear, as previous studies on morphology and limited molecular markers have generated conflicting results. This study unraveled the complex evolutionary history of eight zokor species in China based on de novo assembly at chromosome level and whole-genome sequencing of 23 populations. We found extensive phylogenetic discordances between nuclear and mitochondrial phylogenies, and different coalescent phylogenies, which could be explained by introgression and incomplete lineage sorting (ILS). The recent Qinghai-Tibet Plateau uplift (∼3.60 million y ago; Mya) drove Eospalax to speciate into clade A and clade B (∼3.22 Mya), and discordant phylogenies in this node were mainly attributed to introgression rather than ILS. Clade A rapidly diverged into three lineages due to geographical isolation and glaciation, while glaciation and C4 plant expansion contributed to the speciation of clade B. ILS contributed to the discordances of two rapidly radiated nodes rather than introgression. The effective population sizes (Ne's) of all the species of Eospalax were affected by three glaciations. Ancient polymorphisms and divergence hitchhiking contribute to genomic islands of all the species pairs. Positively selected genes putatively related to specific inhabitation adaptations were identified, such as heart development, neurogenesis, DNA repair, and immune response. Climate, geological tectonism, and C4 vegetation shaped the adaptation and speciation of zokors in China.

Genomic structural variation is associated with hypoxia adaptation in high-altitude zokors.

Zokors, an Asiatic group of subterranean rodents, originated in lowlands and colonized high-elevational zones following the uplift of the Qinghai-Tibet plateau about 3.6 million years ago. Zokors live at high elevation in subterranean burrows and experience hypobaric hypoxia, including both hypoxia (low oxygen concentration) and hypercapnia (elevated partial pressure of CO2). Here we report a genomic analysis of six zokor species (genus Eospalax) with different elevational ranges to identify structural variants (deletions and inversions) that may have contributed to high-elevation adaptation. Based on an assembly of a chromosome-level genome of the high-elevation species, Eospalax baileyi, we identified 18 large inversions that distinguished this species from congeners native to lower elevations. Small-scale structural variants in the introns of EGLN1, HIF1A, HSF1 and SFTPD of E. baileyi were associated with the upregulated expression of those genes. A rearrangement on chromosome 1 was associated with altered chromatin accessibility, leading to modified gene expression profiles of key genes involved in the physiological response to hypoxia. Multigene families that underwent copy-number expansions in E. baileyi were enriched for autophagy, HIF1 signalling and immune response. E. baileyi show a significantly larger lung mass than those of other Eospalax species. These findings highlight the key role of structural variants underlying hypoxia adaptation of high-elevation species in Eospalax.