Your browser doesn't support javascript.
loading
Evolution of Human-Specific Alleles Protecting Cognitive Function of Grandmothers.
Saha, Sudeshna; Khan, Naazneen; Comi, Troy; Verhagen, Andrea; Sasmal, Aniruddha; Diaz, Sandra; Yu, Hai; Chen, Xi; Akey, Joshua M; Frank, Martin; Gagneux, Pascal; Varki, Ajit.
Afiliación
  • Saha S; Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine, Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center, University of California San Diego, San Diego, CA 92093, USA.
  • Khan N; Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine, Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center, University of California San Diego, San Diego, CA 92093, USA.
  • Comi T; Department of Genetics, Princeton University, Princeton, NJ 08544, USA.
  • Verhagen A; Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine, Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center, University of California San Diego, San Diego, CA 92093, USA.
  • Sasmal A; Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine, Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center, University of California San Diego, San Diego, CA 92093, USA.
  • Diaz S; Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine, Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center, University of California San Diego, San Diego, CA 92093, USA.
  • Yu H; Department of Chemistry, University of California Davis, Davis, CA 95616, USA.
  • Chen X; Department of Chemistry, University of California Davis, Davis, CA 95616, USA.
  • Akey JM; Department of Genetics, Princeton University, Princeton, NJ 08544, USA.
  • Frank M; Biognos AB, Gothenburg SE-402 74, Sweden.
  • Gagneux P; Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine, Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center, University of California San Diego, San Diego, CA 92093, USA.
  • Varki A; Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine, Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center, University of California San Diego, San Diego, CA 92093, USA.
Mol Biol Evol ; 39(8)2022 08 03.
Article en En | MEDLINE | ID: mdl-35809046
The myelomonocytic receptor CD33 (Siglec-3) inhibits innate immune reactivity by extracellular V-set domain recognition of sialic acid (Sia)-containing "self-associated molecular patterns" (SAMPs). We earlier showed that V-set domain-deficient CD33-variant allele, protective against late-onset Alzheimer's Disease (LOAD), is derived and specific to the hominin lineage. We now report multiple hominin-specific CD33 V-set domain mutations. Due to hominin-specific, fixed loss-of-function mutation in the CMAH gene, humans lack N-glycolylneuraminic acid (Neu5Gc), the preferred Sia-ligand of ancestral CD33. Mutational analysis and molecular dynamics (MD)-simulations indicate that fixed change in amino acid 21 of hominin V-set domain and conformational changes related to His45 corrected for Neu5Gc-loss by switching to N-acetylneuraminic acid (Neu5Ac)-recognition. We show that human-specific pathogens Neisseria gonorrhoeae and Group B Streptococcus selectively bind human CD33 (huCD33) as part of immune-evasive molecular mimicry of host SAMPs and that this binding is significantly impacted by amino acid 21 modification. In addition to LOAD-protective CD33 alleles, humans harbor derived, population-universal, cognition-protective variants at several other loci. Interestingly, 11 of 13 SNPs in these human genes (including CD33) are not shared by genomes of archaic hominins: Neanderthals and Denisovans. We present a plausible evolutionary scenario to compile, correlate, and comprehend existing knowledge about huCD33-evolution and suggest that grandmothering emerged in humans.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hominidae / Abuelos Límite: Animals / Humans Idioma: En Revista: Mol Biol Evol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hominidae / Abuelos Límite: Animals / Humans Idioma: En Revista: Mol Biol Evol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos