This study presents methods for detecting nonneutral substitution rates in mammalian phylogenies, focusing on identifying functional elements in genomic sequences. The authors developed phyloP, a program that implements four statistical tests: a likelihood ratio test, a score test, a test based on exact distributions of substitutions, and the genomic evolutionary rate profiling (GERP) test. These tests are used to detect conservation (slower evolution) or acceleration (faster evolution) in genomic sequences. The methods were evaluated using simulations and applied to mammalian genomic data from the ENCODE project. The results show that all four tests have similar statistical power, with good sensitivity for detecting strong selection at individual nucleotides, moderate selection in 3-bp elements, and weaker or clade-specific selection in longer elements. The study also introduces new "Conservation" tracks in the UCSC Genome Browser that display phyloP and phastCons scores for 44 vertebrate species. The results suggest that phyloP is a useful tool for identifying functional elements in mammalian genomes, with good performance for detecting conservation and acceleration in various genomic regions. The study highlights the importance of considering both conservation and acceleration in phylogenetic analysis and provides a framework for further research in this area.This study presents methods for detecting nonneutral substitution rates in mammalian phylogenies, focusing on identifying functional elements in genomic sequences. The authors developed phyloP, a program that implements four statistical tests: a likelihood ratio test, a score test, a test based on exact distributions of substitutions, and the genomic evolutionary rate profiling (GERP) test. These tests are used to detect conservation (slower evolution) or acceleration (faster evolution) in genomic sequences. The methods were evaluated using simulations and applied to mammalian genomic data from the ENCODE project. The results show that all four tests have similar statistical power, with good sensitivity for detecting strong selection at individual nucleotides, moderate selection in 3-bp elements, and weaker or clade-specific selection in longer elements. The study also introduces new "Conservation" tracks in the UCSC Genome Browser that display phyloP and phastCons scores for 44 vertebrate species. The results suggest that phyloP is a useful tool for identifying functional elements in mammalian genomes, with good performance for detecting conservation and acceleration in various genomic regions. The study highlights the importance of considering both conservation and acceleration in phylogenetic analysis and provides a framework for further research in this area.