一直关注我们的读者大概会注意到，上次的好文速览栏目好像没有找到。其实不用找了，因为小编尚未来得及写。主要是没有思考好合适的内容做“引子”。小编想着再拖一个月慢慢想，终于，月底爆发的俄乌冲突提供了线索。出乎很多人意料的是，该事件影响迅速波及体育界，一些俄罗斯代表队、运动员以及城市，相继被限制参加或举办部分国际体育赛事（甚至包括国际象棋）【1】。那么，学术圈是否也会有一丝危机？如果有的话，大概从预印本开始吧。

什么意思呢？这就不得不提到著名的由俄国（出生于苏联时期哈萨克斯坦）计算机专家Elbakyan开发的黑色预印本scihub【2】。之所以是黑色是因为其获取论文并提供大众下载是违反出版商规定的，而可以与预印本媲美因其提供了免费看文献的途径。相信不少的朋友都用过它下载文献。一份来自阿根廷科学界的调查显示，超过90%的阿根廷科学家曾用其看文献，此外，尽管大多数认为该行为非法，但道义上正确【3】。Elbakyan此前一直因为建立scihub官司缠身，被判缴付数以千万计的罚款，被迫四处躲藏。总之，不知此次危机之后，由建立的scihub在欧美旷日持久的官司是否会有个了解？当然，作为生物信息学从业人员，你或许还有另一隐忧：markov过程以后还能不能用？

再来聊聊本期所选的文章吧。由于是一二月的preprint集合起来总共选择了十篇文章，小编有更大的选择余地，因此特意选取了两篇关于文昌鱼基因组的文章。可能大家对文昌鱼不甚了解，文昌鱼虽然名鱼，实则属于头索动物，是脊椎动物（vertebrates）的近亲，发育生物学的重要模式动物。然而，迄今为止仅一个文昌鱼基因组公布为其研究造成了不便。此外在演化生物学上，一般认为脊椎动物的祖先发生过两次全基因组倍增（genome duplication），于是，对文昌鱼的基因组研究对全基因组倍增之前的脊椎动物祖先基因组的研究很重要（更多文章可见生信人往期推送：再谈基因组倍增的判断标准）。

浙大周琦组：三个新测序文昌鱼（amphioxus）基因组中透露了哪些关于脊索动物演化的奥秘？

Three amphioxus reference genomes reveal gene and chromosome evolution of chordates

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding into the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention or rearrangements between descendants of whole genome duplications (WGDs), which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its 3D chromatin architecture at the onset of zygotic activation, and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes, and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

瑞士洛桑大学（Université de Lausanne）：文昌鱼的小规模基因倍增（关于基因倍增相关主题，详见往期推送：）

Parallel evolution of amphioxus and vertebrate small-scale gene duplications

We present a study of the European amphioxus (Branchiostoma lanceolatum) gene duplications thanks to a new, high-quality genome reference. We find that, despite its overall slow molecular evolution, the amphioxus lineage has had a history of small-scale duplications similar to the one observed in vertebrates. We find parallel gene duplication profiles between amphioxus and vertebrates, and conserved functional constraints in gene duplication. Moreover, amphioxus gene duplicates show levels of expression and patterns of functional specialization similar to the ones observed in vertebrate duplicated genes. We also find strong conservation of gene synteny between two distant amphioxus species, B. lanceolatum and B. floridae, with two major chromosomal rearrangements. In contrast to their slower molecular and morphological evolution, amphioxus small-scale gene duplication history resembles that of the vertebrate lineage both in quantitative and in functional terms.

高等师范生物研究院（Institut de Biologie de l'École Normale Supérieure）：重建624个真核生物的祖先基因组

Reconstruction of hundreds of reference ancestral genomes across the eukaryotic kingdom

Ancestral sequence reconstruction is a fundamental aspect of molecular evolution studies, and can trace small-scale sequence modifications through the evolution of genomes and species. In contrast, fine-grained reconstructions of ancestral genome organisations are still in their infancy, limiting our ability to draw comprehensive views of genome and karyotype evolution. Here we reconstruct the detailed gene contents and organisations of 624 ancestral vertebrate, plant, fungi, metazoan and protist genomes, 183 of which are near-complete chromosomal reconstructions. Reconstructed ancestral genomes are similar to their descendants in terms of gene content as expected and agree precisely with reference cytogenetic and in silico reconstructions when available. By comparing successive ancestral genomes along the phylogenetic tree, we estimate the intra- and inter-chromosomal rearrangement history of all major vertebrate clades at high resolution. This freely available resource introduces the possibility to follow evolutionary processes at genomic scales in chronological order, across multiple clades and without relying on a single extant species as reference.

斯坦福大学Benjamin Good组：肠道细菌的演化对肠道生态的反馈

Eco-evolutionary feedbacks in the human gut microbiome

Gut microbiota can evolve within their hosts on human-relevant timescales. Yet little is known about how these changes influence (or are influenced by) the composition of their surrounding community. Here, by combining ecological and evolutionary analyses of a large cohort of human gut metagenomes, we show that the short-term evolution of the microbiota is linked with shifts in its ecological structure. These correlations are not simply explained by expansions of the evolving species, and often involve additional fluctuations in distantly related taxa. We show that similar feedbacks naturally emerge in simple resource competition models, even in the absence of cross-feeding or predation. These results suggest that the structure and function of host microbiota may be shaped by their local evolutionary history, with potential implications for personalized medicine and disease.

加州大学三藩分校（UCSF）Sneddon：胎儿胰腺发育的多组学分析

Single-Cell Multi-Omic Roadmap of Human Fetal Pancreatic Development

The critical cellular transitions that govern human pancreas development are largely unknown. We performed large-scale single-cell RNA-sequencing (scRNA-Seq) to interrogate human fetal pancreas development from 8-20 weeks post conception. We identified 103 distinct cell types, including four novel endocrine progenitor subtypes displaying unique transcriptional features and differentiation potency. Integration with single-nucleus Assay for Transposase Accessible Chromatin Sequencing (snATAC-Seq) identified candidate regulators of human endocrine cell fate and revealed development-specific regulatory annotation at diabetes risk loci. Comparison of in vitro stem cell-derived and endogenous endocrine cells predicted aberrant genetic programs leading to the generation of off-target cells. Finally, knock-out studies revealed that the gene FEV regulates human endocrine differentiation. This work establishes a roadmap of human pancreatic development, highlights previously unappreciated cellular diversity and lineage dynamics, and provides a blueprint for understanding pancreatic disease and physiology, as well as generating human stem cell-derived islet cells in vitro for regenerative medicine purposes.

南加州大学：转录组关联分析中遗传多样性的重要性

Multi-ancestry fine-mapping improves precision to identify causal genes in transcriptome-wide association studies

Transcriptome-wide association studies (TWAS) are a powerful approach to identify genes whose expression associates with complex disease risk. However, non-causal genes can exhibit association signals due to confounding by linkage disequilibrium patterns (LD) and eQTL pleiotropy at genomic risk regions which necessitates fine-mapping of TWAS signals. Here, we present MA-FOCUS, a multi-ancestry framework for the improved identification of genes underlying traits of interest. We demonstrate that by leveraging differences in ancestry-specific patterns of LD and eQTL signals, MA-FOCUS consistently outperforms single-ancestry fine-mapping approaches with equivalent total sample size across multiple metrics. We perform 15 blood trait TWAS using genome-wide summary statistics (average NEA=511k, NAA=13k) and lymphoblastoid cell line eQTL data from cohorts of primarily European and African continental ancestries. We recapitulate evidence demonstrating shared genetic architectures for eQTL and blood traits between the two ancestry groups and observe that gene-level effects correlate 20% more strongly across ancestries compared with SNP-level effects. We perform fine-mapping using MA-FOCUS and find evidence that genes at TWAS risk regions are more likely to be shared across ancestries rather than ancestry-specific. Using multiple lines of evidence to validate our findings, we find gene sets produced by MA-FOCUS are more enriched in hematopoietic categories compared to alternative approaches. Our work demonstrates that including, and appropriately accounting for, genetic diversity can drive deeper insights into the genetic architecture of complex traits.

灭绝动物西西里狼的古基因组测序与全科动物的演化

Genomes of the extinct Sicilian wolf reveal a complex history of isolation and admixture with ancient dogs

There are only seven known Sicilian wolf specimens from the 19th and 20th century preserved in museums in Italy and recent morphometric analyses assigned them to the new subspecies Canis lupus cristaldii 10. To better understand the origins of the Sicilian wolf, and its relationship to other wolf populations, we sequenced four whole genomes (3.8×-11.6×) and five mitogenomes. We investigated the relationship between Sicilian wolves and other modern breeds to identify potential admixture. Furthermore, considering that the last land-bridge between Sicily and Italy disappeared after the LGM 11, around 17 kya, we explored the possibility that the Sicilian wolf retained ancestry from ancient wolf and dog lineages. Additionally, we explored whether the long-term isolation might have affected the genomic diversity, inbreeding levels and genetic load of the Sicilian wolf. Our findings show that the Sicilian wolves shared most ancestry with the modern Italian wolf population but are better modelled as admixed with European dog breeds, and shared traces of Eneolithic and Bronze age European dogs. We also find signatures of severe inbreeding and low genomic diversity at population and individual levels due to long-term isolation and drift, suggesting also low effective population size.

耶鲁大学学者推出单基因水平细胞通讯与空间转录组研究新软件NICHES

Comprehensive visualization of cell-cell interactions in single-cell and spatial transcriptomics with NICHES

Summary Recent years have seen the release of several toolsets that reveal cell-cell interactions from single-cell data. However, all existing approaches leverage mean celltype gene expression values, and do not preserve the single-cell fidelity of the original data. Here, we present NICHES (Niche Interactions and Communication Heterogeneity in Extracellular Signaling), a tool to explore extracellular signaling at the truly single-cell level. NICHES allows embedding of ligand-receptor signal proxies to visualize heterogeneous signaling archetypes within cell clusters, between cell clusters, and across experimental conditions. When applied to spatial transcriptomic data, NICHES can be used to reflect local cellular microenvironment. NICHES can operate with any list of ligand-receptor signaling mechanisms and is compatible with existing single-cell packages and pseudotime techniques. NICHES is also a user friendly and extensible program, allowing rapid analysis of cell-cell signaling at single-cell resolution.

以色列威茨曼科学研究所（Weizmann Institute of Science）：36年来野生小麦种群遗传结构的稳定，超强的适应还是有限的扩散？

The genetic structure of a wild wheat population has remained associated with microhabitats over 36 years

Wild progenitors of major crops can help us understand domestication, and may also provide the genetic resources needed for ensuring food security in the face of climate change. We examined the genetic structure of a wild emmer wheat population, sampled over 36 years while both temperature and CO2 concentration increased significantly. The genotypes of 832 individuals revealed high genetic diversity over scales of tens of meters and were clustered spatially into ecological microhabitats. This pattern was remarkably stable over time. Simulations indicate that neutral processes alone are unlikely to fully explain the spatial and temporal stability of the population. These results are consistent with a role for local adaptation in shaping the fine-scale structure of plant populations, which is relevant for in-situ conservation strategies of biodiversity in nature.

美国学者在德州报道人-鹿（圈养）之间的新冠病毒传播

High seroprevalence of SARS-CoV-2 in white-tailed deer (Odocoileus virginianus) at one of three captive cervid facilities in Texas

Free-ranging white-tailed deer (Odocoileus virginanus) across the United States are increasingly recognized as involved in SARS-CoV-2 transmission cycles. Through a cross-sectional study of 80 deer at three captive cervid facilities in central and southern Texas, we provide evidence of 34 of 36 (94.4%) white-tailed deer at a single captive cervid facility seropositive for SARS-CoV-2 by neutralization assay (PRNT90), with endpoint titers as high as 1280. In contrast, all tested white-tailed deer and axis deer (Axis axis) at two other captive cervid facilities were seronegative, and SARS-CoV-2 RNA was not detected in respiratory swabs from deer at any of the three facilities. These data support transmission among captive deer that cannot be explained by human contact for each infected animal, as only a subset of the seropositive does had direct human contact. The facility seroprevalence was more than double of that reported from wild deer, suggesting that the confined environment may facilitate transmission. Further exploration of captive cervids and other managed animals for their role in the epizootiology of SARS-CoV-2 is critical for understanding impacts on animal health and the potential for spillback transmission to humans or other animal taxa.

引文

RINA TORCHINSKY. 2022. NPR News. From chess to tennis, global sports organizations distance themselves from Russia

卷心日记, 2018，Sci-hub创始人的故事--一个俄罗斯女孩的坚守与初心

Por Vanina Lombardi. Ciencia y piratería: Entre lo legal y lo moral （科学和盗版：在合法与道义之间）http://www.unsam.edu.ar/tss/ciencia-y-pirateria-entre-lo-legal-y-lo-moral/

Alexandra Elbakyan: ‘The Fight Against Copyright Cannot Be Apolitical’

Shimeld, Sebastian M. and Nicholas D. Holland. “Amphioxus molecular biology: insights into vertebrate evolution and developmental mechanisms.” Canadian Journal of Zoology 83 (2005): 90-100.