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PLoS Genet. 2014 Sep 11;10(9):e1004531. doi: 10.1371/journal.pgen.1004531. eCollection 2014 Sep.

Positive selection and multiple losses of the LINE-1-derived L1TD1 gene in mammals suggest a dual role in genome defense and pluripotency.

Author information

1
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
2
Department of Biological Sciences & Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho, United States of America.
3
Max-Planck Institute for Evolutionary Biology, Plön, Germany.
4
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Abstract

Mammalian genomes comprise many active and fossilized retroelements. The obligate requirement for retroelement integration affords host genomes an opportunity to 'domesticate' retroelement genes for their own purpose, leading to important innovations in genome defense and placentation. While many such exaptations involve retroviruses, the L1TD1 gene is the only known domesticated gene whose protein-coding sequence is almost entirely derived from a LINE-1 (L1) retroelement. Human L1TD1 has been shown to play an important role in pluripotency maintenance. To investigate how this role was acquired, we traced the origin and evolution of L1TD1. We find that L1TD1 originated in the common ancestor of eutherian mammals, but was lost or pseudogenized multiple times during mammalian evolution. We also find that L1TD1 has evolved under positive selection during primate and mouse evolution, and that one prosimian L1TD1 has 'replenished' itself with a more recent L1 ORF1 from the prosimian genome. These data suggest that L1TD1 has been recurrently selected for functional novelty, perhaps for a role in genome defense. L1TD1 loss is associated with L1 extinction in several megabat lineages, but not in sigmodontine rodents. We hypothesize that L1TD1 could have originally evolved for genome defense against L1 elements. Later, L1TD1 may have become incorporated into pluripotency maintenance in some lineages. Our study highlights the role of retroelement gene domestication in fundamental aspects of mammalian biology, and that such domesticated genes can adopt different functions in different lineages.

PMID:
25211013
PMCID:
PMC4161310
DOI:
10.1371/journal.pgen.1004531
[Indexed for MEDLINE]
Free PMC Article

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