Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins

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...

ver descrição completa

Detalhes bibliográficos
Autores: Khan, Naazneen, de Manuel, Marc|||0000-0002-1245-0127, Peyregne, Stephane, Do, Raymond, Prufer, Kay, Marquès i Bonet, Tomàs|||0000-0002-5597-3075, Varki, Nissi, Gagneux, Pascal, Varki, Ajit|||0000-0002-2206-975X
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:231209
Acesso em linha:https://ddd.uab.cat/record/231209
https://dx.doi.org/urn:doi:10.1093/gbe/evaa125
Access Level:acceso abierto
Palavra-chave:Sialic acid
Hominin
Evolution
CD33rSiglecs
Common ancestor
Neanderthal/Denisovan
Great apes
Archaic hominin
id ES_6967be80ea1e3a67f36a88a1706b3e98
oai_identifier_str oai:ddd.uab.cat:231209
network_acronym_str ES
network_name_str España
repository_id_str
spelling Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic HomininsKhan, Naazneende Manuel, Marc|||0000-0002-1245-0127Peyregne, StephaneDo, RaymondPrufer, KayMarquès i Bonet, Tomàs|||0000-0002-5597-3075Varki, NissiGagneux, PascalVarki, Ajit|||0000-0002-2206-975XSialic acidHomininEvolutionCD33rSiglecsCommon ancestorNeanderthal/DenisovanGreat apesArchaic homininHuman-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. 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/231209https://dx.doi.org/urn:doi:10.1093/gbe/evaa125reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 BFU2017-86471-PAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-880open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2312092026-06-06T12:50:31Z
dc.title.none.fl_str_mv Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins
title Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins
spellingShingle Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins
Khan, Naazneen
Sialic acid
Hominin
Evolution
CD33rSiglecs
Common ancestor
Neanderthal/Denisovan
Great apes
Archaic hominin
title_short Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins
title_full Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins
title_fullStr Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins
title_full_unstemmed Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins
title_sort Multiple genomic events altering Hominin SIGLEC biology and innate immunity predated the common ancestor of humans and archaic Hominins
dc.creator.none.fl_str_mv Khan, Naazneen
de Manuel, Marc|||0000-0002-1245-0127
Peyregne, Stephane
Do, Raymond
Prufer, Kay
Marquès i Bonet, Tomàs|||0000-0002-5597-3075
Varki, Nissi
Gagneux, Pascal
Varki, Ajit|||0000-0002-2206-975X
author Khan, Naazneen
author_facet Khan, Naazneen
de Manuel, Marc|||0000-0002-1245-0127
Peyregne, Stephane
Do, Raymond
Prufer, Kay
Marquès i Bonet, Tomàs|||0000-0002-5597-3075
Varki, Nissi
Gagneux, Pascal
Varki, Ajit|||0000-0002-2206-975X
author_role author
author2 de Manuel, Marc|||0000-0002-1245-0127
Peyregne, Stephane
Do, Raymond
Prufer, Kay
Marquès i Bonet, Tomàs|||0000-0002-5597-3075
Varki, Nissi
Gagneux, Pascal
Varki, Ajit|||0000-0002-2206-975X
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Sialic acid
Hominin
Evolution
CD33rSiglecs
Common ancestor
Neanderthal/Denisovan
Great apes
Archaic hominin
topic Sialic acid
Hominin
Evolution
CD33rSiglecs
Common ancestor
Neanderthal/Denisovan
Great apes
Archaic hominin
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/231209
https://dx.doi.org/urn:doi:10.1093/gbe/evaa125
url https://ddd.uab.cat/record/231209
https://dx.doi.org/urn:doi:10.1093/gbe/evaa125
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BFU2017-86471-P
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-880
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410028095537152
score 15,301603

Registos relacionados