Gene expansions contributing to human brain evolution DOI Creative Commons
Daniela C. Soto, José M. Uribe‐Salazar, Gulhan Kaya

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Genomic drivers of human-specific neurological traits remain largely undiscovered. Duplicated genes expanded uniquely in the human lineage likely contributed to brain evolution, including increased complexity synaptic connections between neurons and dramatic expansion neocortex. Discovering duplicate is challenging because similarity paralogs makes them prone sequence-assembly errors. To mitigate this issue, we analyzed a complete telomere-to-telomere genome sequence (T2T-CHM13) identified 213 duplicated gene families containing (>98% identity). Positing that important universal features should exist with at least one copy all modern humans exhibit expression brain, narrowed on 362 across thousands ancestrally diverse genomes present transcriptomes. Of these, 38 co-express modules enriched for autism-associated potentially contribute language cognition. We 13 are fixed among show convincing patterns. Using long-read DNA sequencing revealed hidden variation 200 ancestries, uncovering signatures selection not previously identified, possible balancing

Language: Английский

MUC5AC filaments illuminate the structural diversification of respiratory and intestinal mucins DOI Creative Commons

Meital Haberman,

Roman Kamyshinsky, Nava Reznik

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(10)

Published: March 4, 2025

Secreted mucins are multimegadalton glycoprotein polymers that share the function of protecting mucosal tissues but diversified for activities in different organs body. Structural studies secreted complicated by enormous sizes, flexibility, and complex supramolecular assembly modes these glycoproteins. The two major respiratory MUC5AC MUC5B. Here, we present structures a large amino-terminal segment form helical filaments. These filaments differ from filamentous tubular observed previously intestinal mucin MUC2 partial homolog VWF. Nevertheless, support proposed mechanism, based on VWF, how noncovalent interactions between monomers guide disulfide crosslinking to polymers. high-resolution show local limited changes amino acid sequence can profoundly affect higher-order while preserving overall folds polymerization activity Differences likely be functionally significant considering divergence mechanical properties physiological requirements mucins. Determining provides foundation understanding mechanisms which they clean protect lungs. Moreover, structure enables visualization sites human variation disease-associated mutations.

Language: Английский

Citations

0
Mucins and Their Roles in Asthma DOI
Qihua Ye,

Gilda Opoku,

Marika Orlov

et al.

Immunological Reviews, Journal Year: 2025, Volume and Issue: 331(1)

Published: April 30, 2025

ABSTRACT Mucus is a crucial component of airway host defense. For optimal protection, its chief components—the mucins MUC5AC and MUC5B—need to be tightly regulated. Their expression localizes specific secretory epithelial cell types capable producing secreting massive glycopolymers. In asthma, abnormal mucus an important clinical problem that effectively treated with therapies directly target mucins. This review summarizes what known about how mucin gene regulation, protein synthesis, secretion are regulated in healthy asthmatic lungs. Ultimately, better understanding these processes could help identify novel ways preventing or reversing dysfunction.

Language: Английский

Citations

0
Advancing evolutionary medicine with complete primate genomes and advanced biotechnologies DOI
Kaiyue Ma, Xiangyu Yang, Yafei Mao

et al.

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

Published: Dec. 1, 2024

Language: Английский

Citations

3
Deciphering the role of structural variation in human evolution: a functional perspective DOI Creative Commons
Charikleia Karageorgiou, Ömer Gökçümen, Megan Y. Dennis

et al.

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 88, P. 102240 - 102240

Published: Aug. 8, 2024

Advances in sequencing technologies have enabled the comparison of high-quality genomes diverse primate species, revealing vast amounts divergence due to structural variation. Given their large size, variants (SVs) can simultaneously alter function and regulation multiple genes. Studies estimate that collectively more than 3.5% genome is divergent humans versus other great apes, impacting thousands Functional genomics gene-editing tools various model systems recently emerged as an exciting frontier - investigating wide-ranging impacts SVs on molecular, cellular, systems-level phenotypes. This review examines existing research identifies future directions broaden our understanding functional roles phenotypic innovations diversity uniquely human features, ranging from cognition metabolic adaptations.

Language: Английский

Citations

2
A review on the mucus dynamics in the human respiratory airway DOI

Asma Tufail,

Yankun Jiang, Xinguang Cui

et al.

Biomechanics and Modeling in Mechanobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Language: Английский

Citations

2
Gene expansions contributing to human brain evolution DOI Creative Commons
Daniela C. Soto, José M. Uribe‐Salazar, Gulhan Kaya

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Genomic drivers of human-specific neurological traits remain largely undiscovered. Duplicated genes expanded uniquely in the human lineage likely contributed to brain evolution, including increased complexity synaptic connections between neurons and dramatic expansion neocortex. Discovering duplicate is challenging because similarity paralogs makes them prone sequence-assembly errors. To mitigate this issue, we analyzed a complete telomere-to-telomere genome sequence (T2T-CHM13) identified 213 duplicated gene families containing (>98% identity). Positing that important universal features should exist with at least one copy all modern humans exhibit expression brain, narrowed on 362 across thousands ancestrally diverse genomes present transcriptomes. Of these, 38 co-express modules enriched for autism-associated potentially contribute language cognition. We 13 are fixed among show convincing patterns. Using long-read DNA sequencing revealed hidden variation 200 ancestries, uncovering signatures selection not previously identified, possible balancing

Language: Английский

Citations

1