Lange A , Prajal PH, Heames B , Findlay GD, Bornberg-Bauer E
Structural and functional characterization of a putative de novo evolved gene in Drosophila
, 2020

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Comparative genomic studies have repeatedly shown that new protein coding genes can
emerge de novo from previously non-coding DNA. An open question is how and when the
structures of encoded de novo proteins emerge and subsequently evolve. Here, we com-
bine biochemical, genetic and evolutionary analyses to elucidate the structure and function
of goddard (gdrd), a gene which appears to have evolved de novo 40 Mya at the base of the
Drosophila genus. While previous studies have demonstrated that gdrd is required for male
fertility, we now pinpoint the defect caused by gdrd mutants as occurring during late sper-
matogenesis, and characterize the failure of elongated spermatids to undergo individualiza-
tion. Structural modelling, together with experimental data, show that Gdrd protein contains
a large central α-helix, but is otherwise mostly disordered as expected given its emergence
from non-coding sequence. We compared its predicted structure with orthologs from diver-
gent fly species, and their reconstructed ancestral sequences, identifying the same α-helix
in all examined ancestral and extant sequences. Accordingly, Gdrd’s structure appears to
have been maintained, with only minor changes at its termini, over millions of years. While it
remains uncertain at which point Gdrd’s function became required for sperm production, we
hypothesize that Gdrd’s initial protein structure was largely similar to its present day struc-
ture, and that this initial structure contributed to the protein’s retention by selection.