{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T05:32:53Z","timestamp":1777267973297,"version":"3.51.4"},"reference-count":69,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Prions are proteinaceous particles that can propagate an alternative conformation to further copies of the same protein. They have been described in mammals, fungi, bacteria and archaea. Furthermore, across diverse organisms from bacteria to eukaryotes, prion-like proteins that have similar sequence characters are evident. Such prion-like proteins have been linked to pathomechanisms of amyotrophic lateral sclerosis (ALS) in humans, in particular TDP43, FUS, TAF15, EWSR1 and hnRNPA2. Because of the desire to study human disease-linked proteins in model organisms, and to gain insights into the functionally important parts of these proteins and how they have changed across hundreds of millions of years of evolution, we analyzed how the sequence traits of these five proteins have evolved across eukaryotes, including plants and metazoa. We discover that the RNA-binding domain architecture of these proteins is deeply conserved since their emergence. Prion-like regions are also deeply and widely conserved since the origination of the protein families for FUS, TAF15 and EWSR1, and since the last common ancestor of metazoa for TDP43 and hnRNPA2. Prion-like composition is uncommon or weak in any plant orthologs observed, however in TDP43 many plant proteins have equivalent regions rich in other amino acids (namely glycine and tyrosine and\/or serine) that may be linked to stress granule recruitment. Deeply conserved low-complexity domains are identified that likely have functional significance.<\/jats:p>","DOI":"10.7717\/peerj.14417","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:25:18Z","timestamp":1668655518000},"page":"e14417","source":"Crossref","is-referenced-by-count":3,"title":["Evolution of sequence traits of prion-like proteins linked to amyotrophic lateral sclerosis (ALS)"],"prefix":"10.7717","volume":"10","author":[{"given":"Jiayi","family":"Luo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul M.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"issue":"1","key":"10.7717\/peerj.14417\/ref-1","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.cell.2009.02.044","article-title":"A systematic survey identifies prions 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