Four classic de novo genes all have plausible homologs and likely evolved from retro-duplicated or pseudogenic sequences

Abstract

Despite being previously regarded as extremely unlikely, the idea that entirely novel protein-coding genes can emerge from non-coding sequences has gradually become accepted over the past two decades. Examples of "de novo origination", resulting in lineage-specific "orphan" genes, lacking orthologs, are now produced every year. However, many are likely cases of duplicates that are difficult to recognize. Here, I re-examine the claims and show that four very well-known examples of genes alleged to have emerged de novo "from scratch" - namely FLJ33706 in humans, Goddard in fruit flies, BSC4 in bakers yeast and AFGP2 in codfish - all have plausible evolutionary ancestors in pre-existing genes. In the case of the first two, highly diverged retrogenes that code for regulatory proteins may have been misidentified as being orphans. The antifreeze glycoproteins in cod, moreover, are shown to have likely not evolved from repetitive non-genic sequences but, as in other related cases, from an apolipoprotein that may well have been pseudogenized before later being reactivated. These findings detract from various claims made about de novo gene birth and show there has been a tendency not to invest the necessary effort in searching for homologs outside of a very limited syntenic or phylostratigraphic methodology. An approach used here for improving homology detection draws upon similarities, not just in terms of statistical sequence analysis, but also with biochemistry and function, in order to obviate failure.