Novelty or Nuisance? Where Lineage-Specific Genes Come From and Why It Matters

Abstract

Lineage-specific” genes, defined operationally as those lacking detected homologs outside of a narrow group of related species, are widely interpreted as novel genes. In this capacity, they have become the subject of significant evolutionary interest seeking to understand the nature and consequences of genetic novelty. Are all or most lineage-specific genes truly evolutionarily novel? Or might there be other, more mundane, reasons that these genes lack homologs beyond their lineage? Here, I explore two sources of lineage-specific genes that do not involve novelty. The first is variation in the genome annotation methods that are used for different species in a comparative analysis; the second is the failure of homology detection algorithms to identify homologs that do actually exist outside of a given lineage. I find evidence that these contribute large numbers of the total lineage-specific genes, suggesting that interpreting lineage-specific genes as novel is not generally reliable. I explore a particular example in which such an interpretation may have confused attempts to understand the evolution of a novel animal trait, and show how an analysis method developed here informs a different interpretation, altering conclusions about evolutionary history. Finally, I review what is known about de novo genes, a particularly poorly-understood type of novel gene.