Dataset Information

Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

ABSTRACT: The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information.

SUBMITTER: Chu XY

PROVIDER: S-EPMC5541315 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

Chu Xin-Yi XY Jiang Ling-Han LH Zhou Xiong-Hui XH Cui Ze-Jia ZJ Zhang Hong-Yu HY

Genes 20170714 7

The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukary ...[more]

PMID: 28708071

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Project description:BACKGROUND: All sequenced genomes contain a proportion of lineage-specific genes, which exhibit no sequence similarity to any genes outside the lineage. Despite their prevalence, the origins and functions of most lineage-specific genes remain largely unknown. As more genomes are sequenced opportunities for understanding evolutionary origins and functions of lineage-specific genes are increasing. RESULTS: This study provides a comprehensive analysis of the origins of lineage-specific genes (LSGs) in Arabidopsis thaliana that are restricted to the Brassicaceae family. In this study, lineage-specific genes within the nuclear (1761 genes) and mitochondrial (28 genes) genomes are identified. The evolutionary origins of two thirds of the lineage-specific genes within the Arabidopsis thaliana genome are also identified. Almost a quarter of lineage-specific genes originate from non-lineage-specific paralogs, while the origins of ~10% of lineage-specific genes are partly derived from DNA exapted from transposable elements (twice the proportion observed for non-lineage-specific genes). Lineage-specific genes are also enriched in genes that have overlapping CDS, which is consistent with such novel genes arising from overprinting. Over half of the subset of the 958 lineage-specific genes found only in Arabidopsis thaliana have alignments to intergenic regions in Arabidopsis lyrata, consistent with either de novo origination or differential gene loss and retention, with both evolutionary scenarios explaining the lineage-specific status of these genes. A smaller number of lineage-specific genes with an incomplete open reading frame across different Arabidopsis thaliana accessions are further identified as accession-specific genes, most likely of recent origin in Arabidopsis thaliana. Putative de novo origination for two of the Arabidopsis thaliana-only genes is identified via additional sequencing across accessions of Arabidopsis thaliana and closely related sister species lineages. We demonstrate that lineage-specific genes have high tissue specificity and low expression levels across multiple tissues and developmental stages. Finally, stress responsiveness is identified as a distinct feature of Brassicaceae-specific genes; where these LSGs are enriched for genes responsive to a wide range of abiotic stresses. CONCLUSION: Improving our understanding of the origins of lineage-specific genes is key to gaining insights regarding how novel genes can arise and acquire functionality in different lineages. This study comprehensively identifies all of the Brassicaceae-specific genes in Arabidopsis thaliana and identifies how the majority of such lineage-specific genes have arisen. The analysis allows the relative importance (and prevalence) of different evolutionary routes to the genesis of novel ORFs within lineages to be assessed. Insights regarding the functional roles of lineage-specific genes are further advanced through identification of enrichment for stress responsiveness in lineage-specific genes, highlighting their likely importance for environmental adaptation strategies.

Dataset Information

Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

Publications

Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

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