fagin: synteny-based phylostratigraphy and finer classification of young genes

Abstract

Background: With every new genome that is sequenced, thousands of species-specific genes (orphans) are found, some originating from ultra-rapid mutations of existing genes, many others originating de novo from non-genic regions of the genome. If some of these genes survive across speciations, then extant organisms will contain a patchwork of genes whose ancestors first appeared at different times. Standard phylostratigraphy, the technique of partitioning genes by their age, is based solely on protein similarity algorithms. However, this approach relies on negative evidence ─ a failure to detect a homolog of a query gene. An alternative approach is to limit the search for homologs to syntenic regions. Then, genes can be positively identified as de novo orphans by tracing them to non-coding sequences in related species. Results: We have developed a synteny-based pipeline in the R framework. Fagin determines the genomic context of each query gene in a focal species compared to homologous sequence in target species. We tested the fagin pipeline on two focal species, Arabidopsis thaliana (plus four target species in Brassicaseae) and Saccharomyces cerevisiae (plus six target species in Saccharomyces). Using microsynteny maps, fagin classified the homology relationship of each query gene against each target genome into three main classes, and further subclasses: AAic (has a coding syntenic homolog), NTic (has a non-coding syntenic homolog), and Unknown (has no detected syntenic homolog). fagin inferred over half the "Unknown" A. thaliana query genes, and about 20% for S. cerevisiae, as lacking a syntenic homolog because of local indels or scrambled synteny. Conclusions: fagin augments standard phylostratigraphy, and extends synteny-based phylostratigraphy with an automated, customizable, and detailed contextual analysis. By comparing synteny-based phylostrata to standard phylostrata, fagin systematically identifies those orphans and lineage-specific genes that are well-supported to have originated de novo. Analyzing within-species genomes should distinguish orphan genes that may have originated through rapid divergence from de novo orphans. Fagin also delineates whether a gene has no syntenic homolog because of technical or biological reasons. These analyses indicate that some orphans may be associated with regions of high genomic perturbation.

Only a Single Taxonomically Restricted Gene Family in the Drosophila melanogaster Subgroup Can Be Identified with High Confidence

“…It is harder to detect homology for shorter and/or faster evolving genes, and this is sufficient to explain at least the qualitative direction of the observed trend. Including synteny information in the phylostratigraphy analysis changes the inferred gene ages ( Arendsee et al. 2019 ), demonstrating that by itself the phylostratigraphy approach is not sufficient.…”

De Novo Gene Birth, Horizontal Gene Transfer, and Gene Duplication as Sources of New Gene Families Associated with the Origin of Symbiosis inAmanita

“…By focusing on younger genes, these studies take advantage of opportunities to trace homologies and syntenies to elucidate the molecular mechanisms of the emergence of new genes ( Donoghue et al. 2011 ; Arendsee et al. 2019 ).…”

Foster thy young: Enhanced prediction of orphan genes in assembled genomes

“…Most protein-coding orphans appear to have arisen de novo from non-protein coding sequence, although various scenarios of defunctionalization and refunctionalization of existing genes provide another origin 1,3,4,27,57 . These youngest, most recentlyformed protein-coding genes, encoding proteins with no amino acid sequence similarity to proteins of any other species, are among the least likely to have been functionally characterized 2 .…”

“…Eukaryotic and prokaryotic genomes contain genes ("orphan genes") whose proteins are recognizable only in a single species; some of these have emerged de novo from the genome, while others have diverged so quickly as to be unrecognizable by homology [1][2][3][4][5][6][7][8][9] . Of the billions of extant orphan genes in eukaryotic species 10 , the precise function of only a few is understood 2, 10-12, 12-19, 19-25 .…”