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The Zoonomia Project has made significant strides in understanding the human genome by identifying highly conserved regions that have remained unchanged for millions of years through the analysis of DNA from 240 mammalian species. This comparative genomics approach provides insights into disease susceptibility, unique mammalian traits, and the genetic basis for rare characteristics such as hibernation and heightened olfactory abilities. Studies highlighted in a recent special issue of Science reveal that about 10% of the human genome is highly conserved, primarily in areas regulating embryonic development and RNA expression. Additionally, researchers correlated genetic variations with the risk of diseases, including cancer, demonstrating that evolutionary conservation can illuminate links between specific mutations and health outcomes. The Zoonomia Project, led by Elinor Karlsson and Kerstin Lindblad-Toh, emphasizes biodiversity conservation, indicating that species with fewer genetic changes at crucial sites may be more vulnerable to extinction. The collaborative effort, involving teams from over 50 institutions, underscores the importance of reference genomes in identifying at-risk species and enhances the understanding of genome evolution. These findings pave the way for future research into both the evolution of genomes and the underlying causes of human diseases.