A high-resolution map of human evolutionary constraint using 29 mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million…

• HU
  Harvard University
• GI
  Gladstone Institutes
• WT
  Wellcome Trust
• EB
  European Bioinformatics Institute
• UU
  Uppsala Universitet
• FO
  Faculty of Arts and Sciences
• CS
  Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology