More Like this

1. Structural and functional characterization of a putative de novo gene in Drosophila

   https://doi.org/10.1038/s41467-021-21667-6  

   Lange, Andreas ; Patel, Prajal H. ; Heames, Brennen ; Damry, Adam M. ; Saenger, Thorsten ; Jackson, Colin J. ; Findlay, Geoffrey D. ; Bornberg-Bauer, Erich ( December 2021 , Nature Communications)

   Abstract Comparative genomic studies have repeatedly shown that new protein-coding genes can emerge de novo from noncoding DNA. Still unknown is how and when the structures of encoded de novo proteins emerge and evolve. Combining biochemical, genetic and evolutionary analyses, we elucidate the function and structure of goddard , a gene which appears to have evolved de novo at least 50 million years ago within the Drosophila genus. Previous studies found that goddard is required for male fertility. Here, we show that Goddard protein localizes to elongating sperm axonemes and that in its absence, elongated spermatids fail to undergo individualization. Combining modelling, NMR and circular dichroism (CD) data, we show that Goddard protein contains a large central α -helix, but is otherwise partially disordered. We find similar results for Goddard’s orthologs from divergent fly species and their reconstructed ancestral sequences. Accordingly, Goddard’s structure appears to have been maintained with only minor changes over millions of years.
2. The goddard and saturn genes are essential for Drosophila male fertility and may have arisen de novo

   https://doi.org/10.1093/molbev/msx057  

   Gubala, Anna M. ; Schmitz, Jonathan F. ; Kearns, Michael J. ; Vinh, Tery T. ; Bornberg-Bauer, Erich ; Wolfner, Mariana F. ; Findlay, Geoffrey D. ( May 2017 , Molecular biology and evolution)

   New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from noncoding DNA sequences. While there are numerous examples of duplicated genes with important func- tional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, we screened 11 putative de novo genes in Drosophila mela- nogaster for effects on male fertility and identified two, goddard and saturn, that are essential for spermatogenesis and sperm function. Goddard knockdown (KD) males fail to produce mature sperm, while saturn KD males produce few sperm, and these function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the noncoding sequences from which each gene arose, we consider goddard and saturn to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specificmore »patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can acquire essential roles in male reproduction.« less
3. Genome analysis of Plectus murrayi , a nematode from continental Antarctica

   https://doi.org/10.1093/g3journal/jkaa045  

   Xue, Xia ; Suvorov, Anton ; Fujimoto, Stanley ; Dilman, Adler R ; Adams, Byron J ( January 2021 , G3 Genes|Genomes|Genetics)

   Félix, M -A (Ed.)

   Abstract Plectus murrayi is one of the most common and locally abundant invertebrates of continental Antarctic ecosystems. Because it is readily cultured on artificial medium in the laboratory and highly tolerant to an extremely harsh environment, P. murrayi is emerging as a model organism for understanding the evolutionary origin and maintenance of adaptive responses to multiple environmental stressors, including freezing and desiccation. The de novo assembled genome of P. murrayi contains 225.741 million base pairs and a total of 14,689 predicted genes. Compared to Caenorhabditis elegans, the architectural components of P. murrayi are characterized by a lower number of protein-coding genes, fewer transposable elements, but more exons, than closely related taxa from less harsh environments. We compared the transcriptomes of lab-reared P. murrayi with wild-caught P. murrayi and found genes involved in growth and cellular processing were up-regulated in lab-cultured P. murrayi, while a few genes associated with cellular metabolism and freeze tolerance were expressed at relatively lower levels. Preliminary comparative genomic and transcriptomic analyses suggest that the observed constraints on P. murrayi genome architecture and functional gene expression, including genome decay and intron retention, may be an adaptive response to persisting in a biotically simplified, yet consistently physically harshmore »environment.« less
4. Predicting gene structure changes resulting from genetic variants via exon definition features

   https://doi.org/10.1093/bioinformatics/bty324  

   Majoros, William H. ; Holt, Carson ; Campbell, Michael S. ; Ware, Doreen ; Yandell, Mark ; Reddy, Timothy E. ; Birol, ed., Inanc ( April 2018 , Bioinformatics)

   Genetic variation that disrupts gene function by altering gene splicing between individuals can substantially influence traits and disease. In those cases, accurately predicting the effects of genetic variation on splicing can be highly valuable for investigating the mechanisms underlying those traits and diseases. While methods have been developed to generate high quality computational predictions of gene structures in reference genomes, the same methods perform poorly when used to predict the potentially deleterious effects of genetic changes that alter gene splicing between individuals. Underlying that discrepancy in predictive ability are the common assumptions by reference gene finding algorithms that genes are conserved, well-formed and produce functional proteins.

   We describe a probabilistic approach for predicting recent changes to gene structure that may or may not conserve function. The model is applicable to both coding and non-coding genes, and can be trained on existing gene annotations without requiring curated examples of aberrant splicing. We apply this model to the problem of predicting altered splicing patterns in the genomes of individual humans, and we demonstrate that performing gene-structure prediction without relying on conserved coding features is feasible. The model predicts an unexpected abundance of variants that create de novo splice sites, an observationmore »supported by both simulations and empirical data from RNA-seq experiments. While these de novo splice variants are commonly misinterpreted by other tools as coding or non-coding variants of little or no effect, we find that in some cases they can have large effects on splicing activity and protein products and we propose that they may commonly act as cryptic factors in disease.

   The software is available from geneprediction.org/SGRF.

   Supplementary information is available at Bioinformatics online.

   « less
5. Molecular mechanism and history of non-sense to sense evolution of antifreeze glycoprotein gene in northern gadids

   https://doi.org/10.1073/pnas.1817138116  

   Zhuang, Xuan ; Yang, Chun ; Murphy, Katherine R. ; Cheng, C. -H. Christina ( February 2019 , Proceedings of the National Academy of Sciences)

   A fundamental question in evolutionary biology is how genetic novelty arises. De novo gene birth is a recently recognized mechanism, but the evolutionary process and function of putative de novo genes remain largely obscure. With a clear life-saving function, the diverse antifreeze proteins of polar fishes are exemplary adaptive innovations and models for investigating new gene evolution. Here, we report clear evidence and a detailed molecular mechanism for the de novo formation of the northern gadid (codfish) antifreeze glycoprotein (AFGP) gene from a minimal noncoding sequence. We constructed genomic DNA libraries for AFGP-bearing and AFGP-lacking species across the gadid phylogeny and performed fine-scale comparative analyses of theAFGPgenomic loci and homologs. We identified the noncoding founder region and a nine-nucleotide (9-nt) element therein that supplied the codons for one Thr-Ala-Ala unit from which the extant repetitive AFGP-coding sequence (cds) arose through tandem duplications. The latent signal peptide (SP)-coding exons were fortuitous noncoding DNA sequence immediately upstream of the 9-nt element, which, when spliced, supplied a typical secretory signal. Through a 1-nt frameshift mutation, these two parts formed a single read-through open reading frame (ORF). It became functionalized when a putative translocation event conferred the essentialcispromoter for transcriptional initiation. We experimentally provedmore »that all genic components of the extant gadidAFGPoriginated from entirely nongenic DNA. The gadidAFGPevolutionary process also represents a rare example of the proto-ORF model of de novo gene birth where a fully formed ORF existed before the regulatory element to activate transcription was acquired.

   « less