Comparative phylogenetic analysis of breast cancer susceptibility genes reveals evolutionary conservation supporting...

Breast cancer susceptibility genes play essential roles in DNA repair, cell-cycle regulation, and tumor suppression. The development of gene-specific DNA barcodes for diagnostic and therapeutic applications requires a clear understanding of the evolutionary conservation and specificity of these genes across related species.

Nucleotide sequences of nine major breast cancer-associated genes (BRCA1, BRCA2, PALB2, ATM, TP53, CHEK2, CDH1, STK11, and BRIP1) were retrieved and analyzed. Orthologous sequences from primate species were identified with BLAST. Multiple sequence alignment was performed, followed by construction of phylogenetic trees using standard distance-based and maximum-likelihood approaches. Trees were visualized and compared to assess evolutionary relationships and gene-level specificity.

All analyzed genes demonstrated clear phylogenetic clustering, with Homo sapiens sequences grouping closely with primate orthologs, particularly Pan troglodytes and Gorilla. Highly conserved genes such as BRCA1, BRCA2, and TP53 showed tight clustering with short branch lengths, whereas moderate variability was observed in genes such as CHEK2 and BRIP1. No cross-gene clustering or unexpected lineage mixing was detected, supporting accurate gene annotation and specificity.

The phylogenetic analyses confirm strong evolutionary conservation of key breast cancer susceptibility genes across primates. These findings support the reliability of gene-derived DNA barcode regions for diagnostic and therapeutic assay development and highlight the importance of evolutionary validation in barcode-based molecular diagnostics.