Biology subjects

Weisman, C. M.

Publications and source records attributed to Weisman, C. M..

6 recordsLinked to original sources

bioRxiv2026

Tinkering loci: genomic hotspots of gene birth and evolutionary innovation

How does evolution create new things? A key strategy is 'tinkering': changing and re-using existing genetic components in new ways. Tinkering is generally conceived of as unpatterned, occurring without spatial or other kinds of structure within the genome. Here, I report 'tinkering loci': distinct genomic regions that significantly accelerate gene birth by tinkering. This occurs because tinkering loci accumulate unusually high concentrations of duplicated gene fragments from around the genome, which they then re-transcribe. Because they bring previously unrelated genes into proximity much more often than expected by chance, they are especially strong accelerants of composite gene creation. I find that tinkering loci are common in Drosophila genomes; vary in number and activity over a few million years; are driven by a standard mutational mechanism acting at all major kinds of transposon sequences; and disperse, as well as receive, duplicates, including their functional products. Tinkering loci demonstrate the possibility of nonrandom genomic patterning of mutations that meaningfully shapes the rates and consequences of molecular innovation. Because these patterns appear at least in part to be themselves encoded in the genome via transposons, which are often genomically abundant and highly dynamic, they suggest a rich and evolvable dimension of genomes that could influence the tempo and mode of animal evolution.

evolutionary biology↗

bioRxiv2025

Exon shuffling hotspots in an animal genome

The birth of new genes is key to evolution. Exon shuffling is a powerful mechanism for gene birth in which new genes are made by stitching together fragments of existing ones. I report hotspots of exon shuffling in the genome of the animal Drosophila affinis. These are relatively small regions that quickly receive, concentrate, and rearrange gene fragments from around the genome. I detail the recent creation of transcripts containing composite open reading frames at these hotspots, including cases that resemble not just the birth of a single gene but of gene families. I describe basic phenomenology of the hotspots and propose that they are best described not specifically in terms of exon shuffling but more broadly by their tendency to toy with existing genomic sequences as "tinkering loci." I speculate that tinkering loci may overcome barriers to the reassortment of modular sequences, accelerating animal evolution.

evolutionary biology↗

bioRxiv2022

Mixing genome annotation methods in a comparative analysis inflates the apparent number of lineage-specific genes

Comparisons of genomes of different species are used to identify lineage-specific genes, those genes that appear unique to one species or clade. Lineage-specific genes are often thought to represent genetic novelty that underlies unique adaptations. Identification of these genes depends not only on genome sequences, but also on inferred gene annotations. Comparative analyses typically use available genomes that have been annotated using different methods, increasing the risk that orthologous DNA sequences may be erroneously annotated as a gene in one species but not another, appearing lineage-specific as a result. To evaluate the impact of such "annotation heterogeneity," we identified four clades of species with sequenced genomes with more than one publicly available gene annotation, allowing us to compare the number of lineage-specific genes inferred when differing annotation methods are used to those resulting when annotation method is uniform across the clade. In these case studies, annotation heterogeneity increases the apparent number of lineage-specific genes by up to 15-fold, suggesting that annotation heterogeneity is a substantial source of potential artifact.

genomics↗

bioRxiv2021

WormCat 2.0 defines characteristics and conservation of poorly annotated genes in Caenorhabditis elegans

Genome-wide measurement of mRNA or protein levels provides broad data sets for biological discovery. However, subsequent computational methods are essential for uncovering the functional implications of the data as well as intuitively visualizing the findings. Current computational tools are biased toward well-described pathways, limiting their utility for novel discovery. Recently, we developed an annotation and category enrichment tool for Caenorhabditis elegans genomic data, WormCat, that provides an intuitive visualization output. Unlike GO, which excludes genes with no annotation information, WormCat 2.0 retains these genes as a special UNASSIGNED category. Here, we show that the UNASSIGNED gene category enrichment exhibits tissue-specific expression patterns and include genes with biological functions. Poorly annotated genes have previously been considered to lack homologs in closely related species. Instead, we find that around 3% of the UNASSIGNED genes have poorly characterized human orthologs. These human orthologs are themselves have little annotation information. A recently developed method that incorporates lineage relationships (abSENSE) indicates that failure of BLAST to detect homology explains the apparent lineage specificity for many UNASSIGNED genes, suggesting that a larger subset could be related to human genes. WormCat provides an annotation strategy that allows association of UNASSIGNED genes with specific phenotypes and known pathways. Our analysis indicates that the UNASSIGNED gene category contains candidates that merit further functional study which could yield insight into understudied areas of biology.

genomics↗

bioRxiv2020

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

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 groups 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.

evolutionary biology↗

bioRxiv2018

Pervasive population genomic consequences of genome duplication in Arabidopsis arenosa

Ploidy-variable species allow direct inference of the effects of chromosome copy number on fundamental evolutionary processes. While an abundance of theoretical work suggests polyploidy should leave distinct population genomic signatures, empirical data remains sparse. We sequenced [~]300 individuals from 39 populations of Arabidopsis arenosa, a naturally diploid-autotetraploid species. We find the impacts of polyploidy on population genomic processes are subtle yet pervasive, including reduced efficiency on linked and purifying selection as well as rampant gene flow from diploids. Initial masking of deleterious mutations, faster rates of nucleotide substitution, and interploidy introgression all conspire to shape the evolutionary potential of polyploids.

evolutionary biology↗