Mol Biol Evol. 2014 Jan;31(1):140-53. doi: 10.1093/molbev/mst184. Epub 2013 Oct 8. Ancient origins of vertebrate-specific innate antiviral immunity.
Animals
deploy various molecular sensors to detect pathogen infections.
RIG-like receptor (RLR) proteins identify viral RNAs and initiate innate immune responses.
The three human RLRs recognize different types of RNA molecules and protect against different viral pathogens. The RLR protein family is widely thought to have originated shortly before the emergence of vertebrates and rapidly diversified through a complex process of domain grafting. Contrary to these findings, here we show that full-length RLRs and their downstream signaling molecules were present in the earliest animals, suggesting that the RLR-based immune system arose with the emergence of multicellularity. Functional differentiation of RLRs occurred early in animal evolution via simple gene duplication followed by modifications of the RNA-binding pocket, many of which may have been adaptively driven. Functional analysis of human and ancestral RLRs revealed that the ancestral RLR displayed RIG-1-like RNA-binding.
MDA5-like binding arose through changes in the RNA-binding pocket following the duplication of the ancestral RLR, which may have occurred either early in Bilateria or later, after deuterostomes split from protostomes.
The sensitivity and specificity with which RLRs bind different RNA structures has repeatedly adapted throughout mammalian evolution, suggesting a long-term evolutionary arms race with viral RNA or other molecules.
- RIG-tyyppinen reseptori RLR . RLR reseptoriproteiinit tunnistavat viruksen RNA muotoa ja panevat alkuun luonnollisen immuniteetin vasteita. Ihmisellä on kolme RLR-muotoa, jotka tunnistavat eri typpisiä RNA molekyylejä ja suojelevat erilaisia viruspatogeeneja vastaan. Arvellaan että RLR- proteiiniperhe on alkuperäisin hieman ennen selkärankaisten laajempaa esiintymistä ja erilaistui nopeasti monimutkaisilla domaaninsiirtoprosesseilla. Näitten löytöjen vastaisesti tutkijat kuitenkin osoittavat, että kokopitkät RLR:t ja niiden alavirtaan signaloivat molekyylit olivat olemassa varhaisimmissa eläimissä, mikä viitaisi siihen, että RLR-perusteinen immuunijärjestelmä sai alkunsa monisoluisuuden ( multicellularity) yhteydessä. RLR:ien funktionaalinen erilaistuminen tapahtui varhain animaalisessa evoluutiossa yksinkertaisilla geeniduplikaatioilla, joita seurasi RNA:ta sitovan taskun modifikaatiot, joista moni toimii adaptoitumalla. Ihmisen RLR:istä ja esi- RLR:istä selviää, että esi-RLR sitoi RNA.ta RIG-1- kaltaisesti. RIG-1 kaltainen RNA.ta sitovuus.
RIG-like receptor (RLR) proteins identify viral RNAs and initiate innate immune responses.
The three human RLRs recognize different types of RNA molecules and protect against different viral pathogens. The RLR protein family is widely thought to have originated shortly before the emergence of vertebrates and rapidly diversified through a complex process of domain grafting. Contrary to these findings, here we show that full-length RLRs and their downstream signaling molecules were present in the earliest animals, suggesting that the RLR-based immune system arose with the emergence of multicellularity. Functional differentiation of RLRs occurred early in animal evolution via simple gene duplication followed by modifications of the RNA-binding pocket, many of which may have been adaptively driven. Functional analysis of human and ancestral RLRs revealed that the ancestral RLR displayed RIG-1-like RNA-binding.
- MDA5- kaltainen sitoutuminen alkoi tapahtua kun RNA:ta sitovassa taskussa tapahtui muutoksia, esi -RLR duplikoitui, mikä lienee tapahtunut varhaisetn Bilateraalisten aikaan tai myöhemmin , kun deuterostomat erosivat protostomista.
MDA5-like binding arose through changes in the RNA-binding pocket following the duplication of the ancestral RLR, which may have occurred either early in Bilateria or later, after deuterostomes split from protostomes.
- RLR:n sensitiivisyys ja spesifisyys erilaisten RNA-struktuurien sitomisessa on toistumiseen adaptoitunut imettäväisten evoluutiossa, mikä viitaa hyvin pitkäaikaiseen evolutionaaliseen kehittymiseen, joka kilpailee virus RNA:n tai muitten molekylien kanssa.
The sensitivity and specificity with which RLRs bind different RNA structures has repeatedly adapted throughout mammalian evolution, suggesting a long-term evolutionary arms race with viral RNA or other molecules.
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