Hi everyone, Katie Pollard from UC Davis Biostatistics will be speaking in Genomics today about what makes us different from chimps ... See below, Mona TITLE: Accelerated and biased nucleotide evolution in the human lineage. SPEAKER: Katherine Pollard, UC Davis, Dept of Statistics/Genome Center TIME: 4:15 LOCATION: Carl Ichan Lab 101 ABSTRACT: Comparative genomics allows us to search the whole human genome for examples of lineage-specific evolution. Using a novel likelihood ratio testing approach, we recently identified 202 Human Accelerated Regions (HARs) that were extensively changed in the last ~6 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. The HARs are mostly non-coding sequences, and the set of genes near HARs is enriched for transcription factors, suggesting a role for HARs in the evolution of human gene regulation. We will describe a few of the most intriguing HARs before turning to a curious observation about the HAR sequences: the most accelerated regions show a striking bias for AT to GC ("weak-to-strong") nucleotide substitutions. To investigate whether this association between rate of substitutions and nucleotide bias is a genome-wide phenomenon, we quantified substitution density and bias across the human and chimp genomes. While there is no weak-to-strong bias overall, clusters of nearby substitutions (5 or more within 300bp) are highly biased. Interestingly, human polymorphisms do not show the same pattern, suggesting a fixation (rather than mutation) bias. We found a strong correlation between nucleotide bias and male recombination rates. This observation will be used to speculate about the cause of rapid, biased evolution in the primate genome and to date the chromosome fusion that formed human chr2.