The adaptive evolution of cancer driver genes.

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.

Cluster expansion of apolipoprotein D (ApoD) genes in teleost fishes.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparative transcriptomics of anal fin pigmentation patterns in cichlid fishes.

BACKGROUND: Understanding the genetic basis of novel traits is a central topic in evolutionary biology. Two novel pigmentation phenotypes, egg-spots and blotches, emerged during the rapid diversification of East African cichlid fishes. Egg-spots are circular pigmentation markings on the anal fins of hundreds of derived haplochromine cichlids species, whereas blotches are patches of conspicuous anal fin pigmentation with ill-defined boundaries that occur in few species that belong to basal cichlid lineages. Both traits play an important role in the breeding behavior of this group of fishes. Knowledge about the origin, homology and underlying genetics of these pigmentation traits is sparse. RESULTS: Here, we present a comparative transcriptomic and differential gene expression analysis of egg-spots and blotches. We first conducted an RNA sequencing experiment where we compared egg-spot tissue with the remaining portion of egg-spot-free fin tissue using six individuals of Astatotilapia burtoni. We identified 1229 differentially expressed genes between the two tissue types. We then showed that rates of evolution of these genes are higher than average estimated on whole transcriptome data. Using quantitative real-time PCR, we found that 29 out of a subset of 46 differentially expressed genes showed an analogous expression pattern in another haplochromine species' egg-spots, Cynotilapia pulpican, strongly suggesting that these genes are involved in the egg-spot phenotype. Among these are the previously identified egg-spot gene fhl2a, two known patterning genes (hoxC12a and bmp3) as well as other pigmentation related genes such as asip. Finally, we analyzed the expression patterns of the same gene subset in two species that feature blotches instead of egg-spots, one haplochromine species (Pseudocrenilabrus philander) and one ectodine species (Callochromis macrops), revealing that the expression patterns in blotches and egg-spots are rather distinct. CONCLUSIONS: We identified several candidate genes that will serve as an important and useful resource for future research on the emergence and diversification of cichlid fishes' egg-spots. Only a limited degree of conservation of gene expression patterns was detected between the egg-spots of the derived haplochromines and blotches from ancestral haplochromines, as well as between the two types of blotches, suggesting an independent origin of these traits.

The impact of laterality on the incidence and prognosis of epithelial ovarian cancer.

INTRODUCTION: Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer, yet the impact of ovarian laterality has received limited attention. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Quaternary climate and environmental changes have shaped genetic differentiation in a Chinese pheasant endemic to the eastern margin of the Qinghai-Tibetan Plateau.

The geological complexity generated by the uplift of the Qinghai-Tibetan Plateau and the resulting habitat heterogeneity have functioned together with climatic oscillations in the Quaternary to have a profound impact on the patterns of genetic diversity and demography of the fauna in this region. To understand the effect of the climatic and environmental shifts of the Quaternary on intraspecific genetic patterns and evolutionary history, we investigated the population genetic structure of the blue eared pheasant (Crossoptilon auritum), an endemic bird inhabiting the easternmost region of the plateau. Our phylogeographic analysis of mitochondrial DNA sequences and eight autosomal microsatellites reveals that the blue eared pheasant is subdivided into four distinct subpopulations: a central group (Huzhu and Taizi Mountains), a southern Zoige group, a southernmost Wanglang group and the northernmost Helan Mountain group. These groups are likely to have diverged in the Pleistocene, corresponding to geological changes and the interglacial-glacial climate oscillations that occurred at the eastern margin of the Qinghai-Tibetan Plateau. These subpopulations thus represent major conservation units, especially for the isolated Helan subpopulation. Our findings provide evidence of population divergence driven by complex Quaternary climate and environmental changes and, once more, highlight the importance of phylogeographic studies for conservation endeavours.