Today's guest post was contributed by Debraj Manna, a postdoctoral researcher and science writer at the Indian Institute of Science in Bangalore, India. Besides his research in non-canonical translation, Debraj is interested in decoding complex scientific discoveries into compelling narratives. He is committed to sharing the stories behind scientific advancements while shedding light on the lives of researchers. He is a member of the Early Career Scientist Multimedia Subcommittee. You can connect with Debraj on X or LinkedIn .

The word “essential” carries weight in genetics: lose the gene, lose the function. Luke Arnce, Jaclyn Bubnell, and Charles Aquadro challenge this intuition in a recent focused comparative study of germline stem-cell (GSC) biology across Drosophila species in G3:Genes|Genomes|Genetics. They tested the famed bag-of-marbles (bam) gene for its conserved function as a switch for daughter cell differentiation into gamete precursors. They then surveyed 366 genes deemed essential for GSC regulation in D. melanogaster. The conclusions are precise and provocative for anyone who uses model species to infer universal rules.

First, the authors examined bam. Using CRISPR-Cas9 to create null alleles in D. americana (a lineage separated from D. melanogaster by roughly 70 million years), the authors found that bam loss causes complete sterility in both sexes and produces the classic tumorous, undifferentiated germline. One copy of wild-type bam rescues fertility, and immunostained ovaries and testes show the expected accumulation of small undifferentiated germ cells in null flies, indicating that bam’s core role in prompting differentiation is ancient and conserved.

Next, they performed the survey. The team mapped orthologs for 366 D. melanogaster GSC genes across 15 additional Drosophila species and two outgroups. They combined Ensembl predictions with a reciprocal best blast hit pipeline, synteny evaluation, and targeted PCR sequencing to validate suspected absences. After conservative filtering and experimental confirmation, approximately 8% of those genes (30 of 366) were absent from at least one species. Absences were not evenly distributed by function: some subsystems, such as the proteasome, remained universally conserved, while other modules showed higher turnover.

A critical nuance emerged along the way: sequence similarity does not reliably predict conserved function. D. americana and D. melanogaster bam proteins share only about 35% amino acid identity, yet both execute the same differentiation switch; conversely, closely looking sequences in other lineages have diverged functionally. The authors also applied population-genetic tests and failed to detect a strong signal of positive selection at bam in D. americana, underscoring heterogeneous selective histories across the genus.

This study is a clear example of developmental systems drift (DSD), in which the outward phenotype (reliable gametogenesis) is conserved while the underlying molecular wiring shifts. The data suggest that genes embedded in large interaction networks may be more dispensable if partner genes compensate, and that synteny-aware validation can distinguish actual gene loss from detection failure. For comparative genomics and evolutionary inference, the message is straightforward: essentiality in a model species and sequence homology are starting points, not final answers.

Together, these findings challenge the assumption that an “essential” gene in one species performs the same role in all its relatives. The fact that key GSC genes can be lost in some flies demonstrates the robustness and flexibility of reproductive gene networks. This flexibility is a hallmark of reproductive gene evolution: fertilization and gametogenesis genes often evolve rapidly, with turnover in which genes take on different roles. Arnce et al.’s study reminds us that evolution can reshuffle its genetic deck: different genetic parts can substitute for each other as long as the end result, producing fertile gametes, is preserved.

References

  • Comparative functional and evolutionary analysis of essential germline stem cell genes across the genus Drosophila and two outgroup species

    Luke R. Arnce, Jaclyn E. Bubnell, Charles F. Aquadro

    G3 Genes|Genomes|Genetics, December 2025; 15(12)

    DOI: 10.1093/g3journal/jkaf224

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