Genes for which homologs can be detected only in a limited group of evolutionarily
related species, called “lineage-specific genes,” are pervasive: essentially every
lineage has them, and they often comprise a sizable fraction of the group’s total genes.
Lineage-specific genes are often interpreted as “novel” genes, representing genetic
novelty born anew within that lineage. Here, we develop a simple method to test an
alternative null hypothesis: that lineage-specific genes do have homologs outside of
the lineage that, even while evolving at a constant rate in a novelty-free manner, have
merely become undetectable by search algorithms used to infer homology. We show
that this null hypothesis is sufficient to explain the lack of detected homologs of a large
number of lineage-specific genes in fungi and insects. However, we also find that a
minority of lineage-specific genes in both clades are not well-explained by this noveltyfree
model. The method provides a simple way of identifying which lineage-specific
genes call for special explanations beyond homology detection failure, highlighting
them as interesting candidates for further study.