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Updated: Apr 12, 2026

An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
The Recent De Novo Origin of Protein C-Termini
Matthew E Andreatta1, Joshua A Levine2, Scott G Foy2
1Department of Ecology & Evolutionary Biology, University of Arizona Present address: Aegis Sciences, Nashville, TN.
Abstract:
Protein-coding sequences can arise either from duplication and divergence of existing sequences, or de novo from noncoding DNA. Unfortunately, recently evolved de novo genes can be hard to distinguish from false positives, making their study difficult. Here, we study a more tractable version of the process of conversion of noncoding sequence into coding: the co-option of short segments of noncoding sequence into the C-termini of existing proteins via the loss of a stop codon. Because we study recent additions to potentially old genes, we are able to apply a variety of stringent quality filters to our annotations of what is a true protein-coding gene, discarding the putative proteins of unknown function that are typical of recent fully de novo genes. We identify 54 examples of C-terminal extensions in Saccharomyces and 28 in Drosophila, all of them recent enough to still be polymorphic. We find one putative gene fusion that turns out, on close inspection, to be the product of replicated assembly errors, further highlighting the issue of false positives in the study of rare events. Four of the Saccharomyces C-terminal extensions (to ADH1, ARP8, TPM2, and PIS1) that survived our quality filters are predicted to lead to significant modification of a protein domain structure.
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