About: Multiple Genomic Events Altering Hominin SIGLEC Biology and Innate Immunity Predated the Common Ancestor of Humans and Archaic Hominins

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About: Multiple Genomic Events Altering Hominin SIGLEC Biology and Innate Immunity Predated the Common Ancestor of Humans and Archaic Hominins Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Multiple Genomic Events Altering Hominin SIGLEC Biology and Innate Immunity Predated the Common Ancestor of Humans and Archaic Hominins
Creator	Varki, Ajit Marques-Bonet, Tomas Gagneux, Pascal De Manuel, Marc Varki, Nissi Do, Raymond Khan, Naazneen Peyregne, Stephane Prufer, Kay
Source	Medline; PMC
abstract	Human-specific pseudogenization of the CMAH gene eliminated the mammalian sialic acid (Sia) Neu5Gc (generating an excess of its precursor Neu5Ac), thus changing ubiquitous cell surface “self-associated molecular patterns” that modulate innate immunity via engagement of CD33-related-Siglec receptors. The Alu-fusion-mediated loss-of-function of CMAH fixed ∼2–3 Ma, possibly contributing to the origins of the genus Homo. The mutation likely altered human self-associated molecular patterns, triggering multiple events, including emergence of human-adapted pathogens with strong preference for Neu5Ac recognition and/or presenting Neu5Ac-containing molecular mimics of human glycans, which can suppress immune responses via CD33-related-Siglec engagement. Human-specific alterations reported in some gene-encoding Sia-sensing proteins suggested a “hotspot” in hominin evolution. The availability of more hominid genomes including those of two extinct hominins now allows full reanalysis and evolutionary timing. Functional changes occur in 8/13 members of the human genomic cluster encoding CD33-related Siglecs, all predating the human common ancestor. Comparisons with great ape genomes indicate that these changes are unique to hominins. We found no evidence for strong selection after the Human–Neanderthal/Denisovan common ancestor, and these extinct hominin genomes include almost all major changes found in humans, indicating that these changes in hominin sialobiology predate the Neanderthal–human divergence ∼0.6 Ma. Multiple changes in this genomic cluster may also explain human-specific expression of CD33rSiglecs in unexpected locations such as amnion, placental trophoblast, pancreatic islets, ovarian fibroblasts, microglia, Natural Killer(NK) cells, and epithelia. Taken together, our data suggest that innate immune interactions with pathogens markedly altered hominin Siglec biology between 0.6 and 2 Ma, potentially affecting human evolution.
has issue date	2020-06-18(xsd:dateTime)
bibo:doi	10.1093/gbe/evaa125
bibo:pmid	32556248
has license	cc-by-nc
sha1sum (hex)	3876b836907a851203e1918c686154e3ad9fda07
schema:url	https://doi.org/10.1093/gbe/evaa125
resource representing a document's title	Multiple Genomic Events Altering Hominin SIGLEC Biology and Innate Immunity Predated the Common Ancestor of Humans and Archaic Hominins
has PubMed Central identifier	PMC7379906
has PubMed identifier	32556248
schema:publication	Genome Biol Evol
resource representing a document's body	covid:3876b836907a851203e1918c686154e3ad9fda07#body_text
is schema:about of	named entity 'genomes' named entity 'modulate' named entity 'human' named entity 'multiple' named entity 'CD33' named entity 'hominid' named entity 'molecular' named entity 'emergence' named entity 'hominin' named entity 'CD33' named entity 'trophoblast' named entity 'altered' named entity 'great ape' named entity 'Multiple' named entity 'generating' named entity 'locations' named entity 'molecular' named entity 'divergence' named entity 'placental' named entity 'major' named entity 'hominins' named entity 'hominin' named entity 'suggested' named entity 'humans' named entity 'strong' named entity 'interactions' named entity 'common ancestor' named entity 'hotspot' named entity 'mutation' named entity 'Natural Killer' named entity 'Neu5Ac' named entity 'genomes' named entity 'pathogens' named entity 'hominin' named entity 'gene' named entity 'CD33' named entity 'fibroblasts' named entity 'Sia' named entity 'Neanderthal' named entity 'glycans' named entity 'Neanderthal' named entity 'Alu' named entity 'pseudogenization' named entity 'innate immune' named entity 'hominins' named entity 'Denisovan' named entity 'CD33' named entity 'Neu5Ac' named entity 'sialic acid' named entity 'genus Homo' named entity 'microglia' named entity 'genomes' named entity 'Innate Immunity' named entity 'Predated' named entity 'beneficial mutation' named entity 'evolution' named entity 'Neu5Gc' named entity 'genetic variation' named entity 'Hublin' named entity 'Neanderthal' named entity 'null mutation' named entity 'gene copy numbers' named entity 'structural variation' named entity 'great apes' named entity 'CMAH' named entity 'microglia' named entity 'Horseradish Peroxidase' named entity 'SIGLEC12' named entity 'cytoplasmic' named entity 'sialic acid' named entity 'mutation' named entity 'genomes' named entity 'human populations'

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