Many, but not all, lineage-specific genes can be explained by homology detection failure

Abstract

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 novelty-free 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.

Universal and taxon-specific trends in protein sequences as a function of age

“…A recent analysis exploited synteny to find that most taxonomically restricted genes are not the product of divergence, but have instead emerged de novo (Vakirlis, Carvunis, and Mclysaght 2019). Another recent study excluded genes with insufficient power to detect ancient homology, and similarly found that evidence for de novo origin persisted in a substantial number of cases (Weisman, Murray, and Eddy 2020). To get correct trends given random failures in homology detection, all we need is for apparent ages to be correlated with true ages.…”

Structural and functional characterization of a putativede novogene inDrosophila

“…Since their initial discovery more than a decade ago [7,55,8], de novo genes and the mechanisms underlying their emergence have been studied intensely. However, concerns regarding the reliability of their computational identification [56,57,58], and if and how they code for functional proteins, have also been raised. We showed previously [30] that Gdrd is likely a de novo evolved gene, supported by its absence from the syntenic regions of outgroup species, the lack of detectably similar proteins in any other taxa, its intronic location, and its high level of intrinsic disorder.…”

Systematic errors in orthology inference and their effects on evolutionary analyses

“…Orthology inference relies on an initial similarity search to identify, among all pairs of genes in two organisms, those that are sufficiently similar to be potentially homologous ( Altenhoff et al, 2019 ). This step can be difficult if two orthologs have diverged significantly ( Jain et al., 2019 ; Weisman et al., 2020 ).…”

“… Moyers and Zhang (2014 , 2017) have, like us, used simulation of gene evolution followed by a phylostratigraphic analysis and showed that faster evolving genes appeared younger than they should—i.e that orthologs of faster genes are less likely to be detected in more distant relatives. Recently, Weisman et al. (2020) showed that supposedly lineage-specific genes within the Drosophila and Saccharomyces genera have undetected homologs outside their respective lineages.…”