Identification of constrained sequence elements across 239 primate genomes

Nature, Journal Year: 2023, Volume and Issue: 625(7996), P. 735 - 742

Published: Nov. 29, 2023

Abstract Noncoding DNA is central to our understanding of human gene regulation and complex diseases 1,2 , measuring the evolutionary sequence constraint can establish functional relevance putative regulatory elements in genome 3–9 . Identifying genomic that have become constrained specifically primates has been hampered by faster evolution noncoding compared protein-coding 10 relatively short timescales separating primate species 11 previously limited availability whole-genome sequences 12 Here we construct a alignment 239 species, representing nearly half all extant order. Using this resource, identified are under selective across other mammals at 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites 267,410 transcription factor binding but not placental validate their cis -regulatory effects on expression. These enriched for genetic variants affect expression traits diseases. Our results highlight important role recent differentiating primates, including humans, from mammals.

Language: Английский

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Structurally divergent and recurrently mutated regions of primate genomes

Cell, Journal Year: 2024, Volume and Issue: 187(6), P. 1547 - 1562.e13

Published: Feb. 29, 2024

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, marmoset. identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes 136,932 regulatory elements, including most complete set human-specific differences. estimate that 819.47 Mbp or ∼27% genome has been affected by SVs across primate evolution. identify 1,607 structurally divergent regions wherein recurrent variation contributes to creating SV hotspots where are recurrently lost (e.g., CARD, C4, OLAH gene families) additional generated CKAP2, VPS36, ACBD7, NEK5 paralogs), becoming targets rapid chromosomal diversification positive selection RGPD family). High-fidelity made these dynamic accessible for sequence-level analyses within between species.

Language: Английский

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Harnessing deep learning for population genetic inference

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 61 - 78

Published: Sept. 4, 2023

Language: Английский

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New phage-based wastewater pollution control solution with safe reuse

Environmental Nanotechnology Monitoring & Management, Journal Year: 2024, Volume and Issue: 21, P. 100951 - 100951

Published: April 12, 2024

Language: Английский

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Generation and characterization of inducible KRAB-dCas9 iPSCs from primates for cross-species CRISPRi

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 110090 - 110090

Published: May 23, 2024

Comparisons of molecular phenotypes across primates provide unique information to understand human biology and evolution, single-cell RNA-seq CRISPR interference (CRISPRi) screens are a powerful approach analyze them. Here, we generate validate three human, gorilla, two cynomolgus iPS cell lines that carry dox-inducible KRAB-dCas9 construct at the AAVS1 locus. We show despite variable expression levels among lines, comparable downregulation target genes phenotypic effects observed in CRISPRi screen. Hence, valuable resources for performing further extending non-human primates.

Language: Английский

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Generation and characterization of induced pluripotent stem cells of small apes

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 19, 2025

Small apes (family Hylobatidae), encompassing gibbons and siamangs, occupy a pivotal evolutionary position within the hominoid lineage, bridging gap between great catarrhine monkeys. Although they possess distinctive genomic phenotypic features-such as rapid chromosomal rearrangements adaptations for brachiation-functional studies on small have been hindered by limited availability of biological samples developmental models. Here, we address this successfully reprogramming primary skin fibroblasts from three ape species: lar (Hylobates lar), Abbott's gray abbotti), siamangs (Symphalangus syndactylus). Using Sendai virus-based stealth RNA vectors, generated 31 reprogrammed cell lines, five which were developed into transgene-free induced pluripotent stem cells. These iPSCs displayed canonical features primed pluripotency, both morphologically molecularly, consistent with other primate iPSCs. Directed differentiation experiments confirmed capacity to generate cells representing all germ layers. In particular, their successful limb bud mesoderm underscores utility in investigating molecular mechanisms unique forelimb evolution. Transcriptomic profiling revealed significant upregulation pluripotency-associated genes, alongside elevated expression transposable elements. Remarkably, LAVA retrotransposons-a class elements specific apes-exhibited particularly high levels these Comparative transcriptomic analyses humans, apes, macaques identified trends clade-specific gene signatures. signatures highlighted processes linked stability death, providing insights ape-specific adaptations. This study positions transformative tool advancing functional genomics biology. By facilitating detailed investigations genome evolution diversification, system bridges critical gaps comparative research, enabling deeper exploration genetic cellular underpinnings traits.

Language: Английский

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Genomic basis of non-human-primate diversity and adaptation

Published: March 31, 2025

Language: Английский

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The impact of human accelerated regions on neuronal development

Trends in Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Human accelerated regions (HARs) are the fastest-evolving sequences in human genome since divergence from chimpanzees. Some of these suspected to have contributed evolution unique brain features. Recently, Cui et al. conducted a large-scale study identifying which HARs may influenced neuronal function.

Language: Английский

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Comparative transcriptome analysis between rhesus macaques (<i>Macaca mulatta</i>) and crab-eating macaques (<i>M. fascicularis</i>)

动物学研究, Journal Year: 2023, Volume and Issue: 45(2), P. 299 - 310

Published: Dec. 28, 2023

Understanding the variations in gene expression between species is pivotal for deciphering evolutionary diversity phenotypes. Rhesus macaques and crab-eating serve as crucial nonhuman primate biomedical models with different phenotypes, but large-scale of comparative transcriptome research these two has yet to be fully elucidated. Here, we conduct systematic comparisons utilizing newly sequenced RNA-seq data from 84 samples (41 Mfa 43 Mmu samples) encompassing 14 common tissues. Our findings reveal that a small fraction genes (~3.7%) show differential macaque species, while ~36.5% tissue-specific both macaques. We also compare humans ~22.6 % orthologous at least 2 Moreover, ~19.41% overlapped macaque-specific structural variants are more likely Of these, FAM220A shows elevated compared because lineage-specific duplication. In summary, our study presents analysis transcriptomes within humans. These insights into will enhance utility contributing broader realm genomic studies.

Language: Английский

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Advancing evolutionary medicine with complete primate genomes and advanced biotechnologies

Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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