Researchers explore the origins of orphan genes

Orphan genes, or taxonomically restricted genes have been a curious thing for researchers. They’ve been the topic of a study published in eLife on Feb. 18, 2020.

Researchers from Trinity College of Dublin, the University of Dublin, and the University of Pittsburgh have been exploring how many times these genes, which do not have homologs, diverge from an ancestral gene to a point where they can be considered orphans.

The researchers, Nikolaos Vakirlis, Anne-Ruxandra Carvunis, and Aoife McLysaght, have considered that there are two dominant explanations for orphan genes: complete sequence divergence from ancestral genes, and de novo emergence from ancestral non-genic sequences, such that homologues do not exist.

They developed a pipeline that allows the identification of candidate homologous genes, regardless of whether or not they could detect pairwise sequence similarity. The idea that informs the pipeline is that genes found in conserved syntenic positions in a pair of genomes will usually share ancestry. That, and the divergence of those biological sequences over time, allow researchers to estimate how many times homologous genes will diverge until there’s no sequence similarity.

They found that in most pairwise species comparisons, the observed proportion of all genes without similarity far exceeds that estimate to have originated by divergence. They also proceeded with a question of whether ancestral similarities persist even when primary homologous sequences have diverged beyond recognition.

“Finally, we investigated how orphan genes that have originated by divergence beyond recognition might impact human biology. Our approach identified thirteen human genes that underwent complete divergence along the human lineage and have no detectable homologues outside of mammals,” they wrote in the eLifeSciences report.

The group noted that they underestimated the number of orphan genes and overestimated the number of orphan genes that were created through divergence. But, they say their findings are “consistent with the view that multiple evolutionary processes are responsible for the existence of orphan genes and suggest that, contrary to what has been assumed, divergence is not the predominant one.”