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BackgroundThe genetic mechanisms of speciation and adaptation in the marine environment are not well understood. The rockfish genus Sebastes provides a unique model system for studying adaptive evolution because of the extensive diversity found within this group, which includes morphology, ecology, and a broad range of life spans. Examples of adaptive radiations within marine ecosystems are considered an anomaly due to the absence of geographical barriers and the presence of gene flow. Using marine rockfishes, we identified signatures of natural selection from transcriptomes developed from gonadal tissue of two rockfish species (Sebastes goodei and S. saxicola). We predicted orthologous transcript pairs, and estimated their distributions of nonsynonymous (Ka) and synonymous (Ks) substitution rates.ResultsWe identified 144 genes out of 1079 orthologous pairs under positive selection, of which 11 are functionally annotated to reproduction based on gene ontologies (GOs). One orthologous pair of the zona pellucida gene family, which is known for its role in the selection of sperm by oocytes, out of ten was identified to be evolving under positive selection. In addition to our results in the protein coding-regions of transcripts, we found substitution rates in 3’ and 5’ UTRs to be significantly lower than Ks substitution rates implying negative selection in these regions.ConclusionsWe were able to identify a series of candidate genes that are useful for the assessment of the critical genes that diverged and are responsible for the radiation within this genus. Genes associated with longevity hold potential for understanding the molecular mechanisms that have contributed to the radiation within this genus.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1870-0) contains supplementary material, which is available to authorized users.

457 Background: Plasma cell-free DNA (pcfDNA) has shown great promise for non-invasive, multi-cancer early detection (MCED), but has lower sensitivity for early-stage urological cancers due to low tumor fraction in plasma. Urine cfDNA (ucfDNA) has the potential to improve detection and monitoring of early-stage urological cancers due to its proximity to the affected organs and ease of collection. We conducted an exploratory study to assess the utility of methylation patterns in ucfDNA to detect BC in patients with suspicious bladder lesions, and compare to detection using matched pcfDNA. Methods: Urine and blood were collected from patients with suspicion of new (N=17) or recurrent (N=20) non-muscle invasive BC (NMIBC), and from non-cancer (NC) patients with urological conditions (N=16). Patients with suspicion of NMIBC were diagnosed and staged by transurethral resection of bladder tumor (TURBT) and conventional imaging. Tumor allele fraction (TAF) estimates from ucfDNA were inferred using a method trained on methylation patterns enriched in BC tissue (N=49) relative to an external reference dataset of NC ucfDNA (N=176). We set a detection threshold, using a maximum TAF value from a separate set of NC urine samples (N=50), to determine ucfDNA sensitivity for detecting BC in our study. Sensitivity in pcfDNA was determined using a validated MCED test classifier at 99% specificity. Results: Of 17 patients with suspicion of new NMIBC, 12 were diagnosed with BC after TURBT (Stage 0: N=6, I: N=5, II: N=1), and 10/12 were high grade (HG). Among patients with confirmed BC, ucfDNA sensitivity was 91.7% overall (11/12; 95% CI 61.5-99.8%) and 90% for HG (9/10). Whereas, pcfDNA sensitivity was 16.7% overall (2/12) and 10.0% for HG (1/10). Of 20 patients with suspicion of recurrent NMIBC, 14 were confirmed as BC (Stage 0: N=10, I: N=2, II: N=2) and 11/14 were HG. Sensitivity of ucfDNA for recurrence detection was 78.6% overall (11/14; 95% CI 49.2-95.3%), and 100% for HG (11/11), while pcfDNA sensitivity was 14.3% (2/14) overall and 18.2% (2/11) for HG. Notably, TAF in urine from NC patients (N=16) and patients with suspicion of new NMIBC found to be benign by TURBT (N=5) were all below the detection threshold. Among patients with suspicion of recurrent NMIBC but not found to have BC by TURBT, TAF estimates for 4/6 (66.7%) were above the detection threshold. Conclusions: We observed increased sensitivity in urine compared to matched plasma in patients with NMIBC, consistent with local shedding of bladder tumors into stored urine. A urine-based cfDNA assay with high sensitivity at high specificity, combined with non-invasive sampling, could be an ideal tool to use alongside the standard of care (e.g., cystoscopy) for clinical diagnosis and monitoring of BC. Further studies are needed to validate these findings and determine the clinical utility of ucfDNA in the diagnosis and surveillance of BC.