Gene and genome duplication play important roles in the evolution of gene function. Compared to individual duplicated genes, gene clusters attract particular attention considering their frequent associations with innovation and adaptation. Here, we report for the first time the expansion of the apolipoprotein D (ApoD) ligand-transporter genes in a cluster manner specific to teleost fishes. Based on comparative genomic and transcriptomic analyses, protein 3D structure comparison, positive selection detection and breakpoints detection, the single ApoD gene in the ancestor expanded into two clusters following a dynamic evolutionary pattern in teleost fishes. Orthologous genes show conserved expression patterns, whereas lineage-specific duplicated genes show tissue-specific expression patterns and even evolve new gene expression profiles. Positive selection occurred in branches before and after gene duplication, especially for lineage-specific duplicated genes. Cluster analyses based on protein 3D structure comparisons, especially comparisons of the four loops at the opening side, show gene duplication-segregating patterns. Duplicated ApoD genes are predicted to be associated with forkhead transcription factors and MAPK genes. ApoD clusters are located next to the breakpoints of genome rearrangements. Here, we report the expansion of ApoD genes specific to teleost fishes in a cluster manner for the first time. Neofunctionalization and subfunctionalization were observed at both the protein and expression levels after duplication. Evidence from different aspects—i.e., abnormal expression-induced disease in humans, fish-specific expansion, predicted associations with forkhead transcription factors and MAPK genes, specific expression patterns in tissues related to sexual selection and adaptation, duplicated genes under positive selection and their location next to the breakpoints of genome rearrangements—suggests the potentially advantageous roles of ApoD genes in teleost fishes. The cluster expansion of ApoD genes specific to teleost fishes provides thus an ideal evo-devo model for studying gene duplication, cluster maintenance and new gene function emergence.

Background: Cancer is a life-threatening disease in humans; yet, cancer genes are frequently reported to be under positive selection. This suggests an evolutionary-genetic paradox in which cancer evolves as a secondary product of selection in human beings. However, systematic investigation of the evolution of cancer driver genes is sparse.Results: Using comparative genomics analysis, population genetics analysis and computational molecular evolutionary analysis, the evolution of 568 cancer driver genes of 66 cancer types were evaluated at two levels, selection on the early evolution of humans (long timescale selection in the human lineage during primate evolution, i.e., millions of years), and recent selection in modern human populations (~ 100,000 years). Results showed that eight cancer genes covering 11 cancer types were under positive selection in the human lineage (long timescale selection). And 35 cancer genes covering 47 cancer types were under positive selection in modern human populations (recent selection). Moreover, SNPs associated with thyroid cancer in three thyroid cancer driver genes (CUX1, HERC2 and RGPD3) were under positive selection in East Asian and European populations, consistent with the high incidence of thyroid cancer in these populations.Conclusions: These findings suggest that cancer can be evolved, in part, as a by-product of adaptive changes in humans. Different SNPs at the same locus can be under different selection pressures in different populations, and thus should be under consideration during precision medicine, especially for targeted medicine in specific populations.

Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer, yet the impact of ovarian laterality has received limited attention. We conducted a comprehensive investigation into the impact of laterality (left-right and bilateral-unilateral) on EOC incidence and prognosis, focusing on distinct subtypes. Binomial tests and Pearson's χ2 tests were employed to compare occurrence rates among laterality groups. Cox regression analyses were used to create a proportional hazards model for tumor prognosis. Nomograms were developed and validated, including internal validation via bootstrapping. Our study encompassed 20,790 EOC patients, revealing disparities in incidence and prognosis between unilateral and bilateral cases. Unilateral tumor development was notably predominant in clear cell, endometrioid, brenner, and mucinous subtypes, while bilateral involvement was more frequent in serous ovarian cancer. Laterality differences, reflecting disparities between the left and right sides, were chiefly evident in the incidence rates across various stages and in the prognosis of specific subtypes. Notably, mucinous ovarian cancer exhibited significantly better prognosis on the right side compared to the left (right tumors: HR = 0.745, p = 0.015, CI: 0.587-0.945). These findings emphasize the importance of considering ovarian laterality -both left-right and bilateral-unilateral aspects -as a critical factor influencing EOC incidence and prognosis, necessitating attention in clinical practice.

Determining whether convergent novelties share a common genetic basis is vital to understanding the extent to which evolution is predictable. The convergent evolution of innovative anal fin pigmentation patterns in cichlid fishes is an ideal model for studying this question. Here, we focused on two patterns: 1) egg-spots, circular pigmentation patterns with different numbers, sizes and positions; and 2) the blotch, irregular pattern with no variation among species. How these two novelties originate and evolve remains unclear. Based on a thorough comparative transcriptomic and genomic analysis, we observed a common genetic basis with high evolutionary rates and similar expression levels between egg-spots and the blotch. But the associations of common genes with transcription factors and signalling pathways in the core gene network, as well as the integration of advantageous genes were observed specifically for egg-spots. Focusing on the whole transcriptomic level instead of limited numbers of candidate genes can explain the opposite conclusion between our study and the one from Santos et al. (2016), which suggested that no common genetic basis is shared between the blotch and egg-spots. Here, we propose that the re-use of the common genetic basis indicates important conservative functions (e.g., toolkit genes) for the origin of these convergent novel phenotypes, whereas independently evolved associations of common genes with transcription factors and signalling pathways (intrinsic factor) can free the evolution of egg-spots, and together with the integration of advantageous genes (extrinsic factor) can provide a clue to link egg-spots as a key innovation to the adaptive radiation in cichlid fishes. This hypothesis will further illuminate the mechanism of the origin and evolution of novelties in a broad sense.

Although depression significantly impacts fitness, some hypotheses suggest that it may offer a survival benefit. However, there has been limited systematic investigation into the selection pressures acting on genes associated with depression at the genomic level. Here, we conducted comparative genomic analyses and computational molecular evolutionary analyses on 320 depression-associated genes at two levels, i.e., across the primate phylogeny (long timescale selection) and in modern human populations (recent selection). We identified seven genes under positive selection in the human lineage, and 46 genes under positive selection in modern human populations. Most positively selected variants in modern human populations were at UTR regions and non-coding exons, indicating the importance of gene expression regulation in the evolution of depression-associated genes. Positively selected genes are not only related to immune responses, but also function in reproduction and dietary adaptation. Notably, the proportion of depression-associated genes under positive selection was significantly higher than the positively selected genes at the genome-wide average level in African, East Asian, and South Asian populations. We also identified two positively selected loci that happened to be associated with depression in the South Asian population. Our study revealed that depression-associated genes are subject to varying selection pressures across different populations. We suggest that, in precision medicine—particularly in gene therapy—it is crucial to consider the specific functions of genes within distinct populations.