Genome nucleotide composition is of fundamental significance in molecular evolution, genome organization and synthetic biology. Albeit studied for decades, it remains unclear whether there is any theoretical law underlying variable genome nucleotide composition across different species. From the mathematical viewpoint, here we propose three laws of genome nucleotide composition and validate their effectiveness on a large collection of empirical genome sequences across three domains of life. The three laws together provide a unifying framework that is able to unravel the mystery of genome-wide nucleotide composition variation across diverse species, paving the way towards a new era with quantitative insights for deciphering basic principles of life and further advancing theoretical biology. One-Sentence SummaryThe three laws of genome nucleotide composition provide a fundamental framework for molecular evolution, genome organization and synthetic biology.
