 |
Research Summary Publication (PMID 385509983): Song JH, Dávalos LM, MacCarthy T, Damaghi M. Evolvability of cancer-associated genes under APOBEC3A/B selection. iScience. 2024 Mar 6;27(4):109433. doi: 10.1016/j.isci.2024.109433. PMID: 38550998; PMCID: PMC10972820.Topic: Evolution of cancer susceptibility, evolution of sequence motifs, multi-species comparisons Understanding the factors driving the initiation and progression of cancers is crucial for predicting clinical outcomes and designing effective treatments. One such factor is tumor genetic heterogeneity, which is influenced by susceptibility of the genome to mutations. Certain enzymes are known to contribute to this susceptibility, but it is not fully understood how this impacts the evolution of the genome or the cancer-associated subset of genes therein. The authors surveyed 40,000 human transcripts for patterns of susceptibility related to one such enzyme, APOBEC3A/B. The human transcriptome is skewed towards robustness against the effects of mutations, but cancer-related genes have a distinct, bimodal pattern of evolvability. These overall patterns are mirrored in a bat species (which are long-lived and have low cancer incidence), as well as other surveyed species. Looking at a set of cancer gene orthologs in 10 vertebrate species, authors found that genes can have a range of tolerance to mutagenesis while maintaining functionality. |
Current CGR Impact on Research
The authors’ work was facilitated by easily obtaining open-access, high quality data using:
Potential CGR Impact on ResearchCGR resources and capabilities, including further use of Datasets and Orthologs, could extend this work and benefit other researchers with similar workflows and data needs. For example:The following are examples of how CGR resources and capabilities could impact this study.NCBI Datasets Command Line Interface: Ease of downloading orthologs and whole-genome scale data, including coding regions, could enable study of more organisms or gene families. Researchers can focus on biological reasons for choosing taxa rather than difficulty of finding data. Datasets functionality is also available via web and on Galaxy. NCBI Orthologs: Find additional pre-computed orthologs of this gene family and families related to mutational susceptibility in potential experimental models, outside of the vertebrates already considered. NCBI Orthologs covers a wide range of genes and taxa, including a recent addition of two million insect genes. Comparative Genome Viewer: Visually explore synteny using pre-computed alignments, such as between a human and a bat, to examine spatial relationships of members of the target gene family and other genes with this motif. Users can request pairwise alignments of chromosome-level, NCBI-hosted genome assemblies for their species of interest if they don’t exist yet. As more high-quality genomes are submitted to NCBI, more pairwise alignments will be possible. |
