期刊
BMC EVOLUTIONARY BIOLOGY
卷 12, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2148-12-114
关键词
Positive selection; Colon cancer; Adaptive evolution; Protein functional shift; Selective pressure; Evolutionary medicine
资金
- Irish Research Council for Science, Engineering and Technology (Embark Initiative Postgraduate Scholarship) [RS2000172]
- DCU O'Hare scholarship
- School of Biotechnology and Pierse Trust Scholarships at DCU
- Science Foundation Ireland [RFP: EOB2673]
- SFI Travel fellowship [10/RFP/EOB2673 - STTF 11]
- Science Foundation Ireland (SFI) [10/RFP/EOB2673, 10/RFP/EOB2673 - STTF 11] Funding Source: Science Foundation Ireland (SFI)
Background: Cancer, much like most human disease, is routinely studied by utilizing model organisms. Of these model organisms, mice are often dominant. However, our assumptions of functional equivalence fail to consider the opportunity for divergence conferred by similar to 180 Million Years (MY) of independent evolution between these species. For a given set of human disease related genes, it is therefore important to determine if functional equivalency has been retained between species. In this study we test the hypothesis that cancer associated genes have different patterns of substitution akin to adaptive evolution in different mammal lineages. Results: Our analysis of the current literature and colon cancer databases identified 22 genes exhibiting colon cancer associated germline mutations. We identified orthologs for these 22 genes across a set of high coverage (>6X) vertebrate genomes. Analysis of these orthologous datasets revealed significant levels of positive selection. Evidence of lineage-specific positive selection was identified in 14 genes in both ancestral and extant lineages. Lineage-specific positive selection was detected in the ancestral Euarchontoglires and Hominidae lineages for STK11, in the ancestral primate lineage for CDH1, in the ancestral Murinae lineage for both SDHC and MSH6 genes and the ancestral Muridae lineage for TSC1. Conclusion: Identifying positive selection in the Primate, Hominidae, Muridae and Murinae lineages suggests an ancestral functional shift in these genes between the rodent and primate lineages. Analyses such as this, combining evolutionary theory and predictions - along with medically relevant data, can thus provide us with important clues for modeling human diseases.
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