Author:
Christmas Matthew J.,Kaplow Irene M.,Genereux Diane P.,Dong Michael X.,Hughes Graham M.,Li Xue,Sullivan Patrick F.,Hindle Allyson G.,Andrews Gregory,Armstrong Joel C.,Bianchi Matteo,Breit Ana M.,Diekhans Mark,Fanter Cornelia,Foley Nicole M.,Goodman Daniel B.,Goodman Linda,Keough Kathleen C.,Kirilenko Bogdan,Kowalczyk Amanda,Lawless Colleen,Lind Abigail L.,Meadows Jennifer R. S.,Moreira Lucas R.,Redlich Ruby W.,Ryan Louise,Swofford Ross,Valenzuela Alejandro,Wagner Franziska,Wallerman Ola,Brown Ashley R.,Damas Joana,Fan Kaili,Gatesy John,Grimshaw Jenna,Johnson Jeremy,Kozyrev Sergey V.,Lawler Alyssa J.,Marinescu Voichita D.,Morrill Kathleen M.,Osmanski Austin,Paulat Nicole S.,Phan BaDoi N.,Reilly Steven K.,Schäffer Daniel E.,Steiner Cynthia,Supple Megan A.,Wilder Aryn P.,Wirthlin Morgan E.,Xue James R.,Birren Bruce W.,Gazal Steven,Hubley Robert M.,Koepfli Klaus-Peter,Marques-Bonet Tomas,Meyer Wynn K.,Nweeia Martin,Sabeti Pardis C.,Shapiro Beth,Smit Arian F. A.,Springer Mark,Teeling Emma,Weng Zhiping,Hiller Michael,Levesque Danielle L.,Lewin Harris A.,Murphy William J.,Navarro Arcadi,Paten Benedict,Pollard Katherine S.,Ray David A.,Ruf Irina,Ryder Oliver A.,Pfenning Andreas R.,Lindblad-Toh Kerstin,Karlsson Elinor K.,
Abstract
AbstractEvolutionary constraint and acceleration are powerful, cell-type agnostic measures of functional importance. Previous studies in mammals were limited by species number and reliance on human-referenced alignments. We explore the evolution of placental mammals, including humans, through reference-free whole-genome alignment of 240 species and protein-coding alignments for 428 species. We estimate 10.7% of the human genome is evolutionarily constrained. We resolve constraint to single nucleotides, pinpointing functional positions, and refine and expand by over seven-fold the catalog of ultraconserved elements. Overall, 48.5% of constrained bases are as yet unannotated, suggesting yet-to-be-discovered functional importance. Using species-level phenotypes and an updated phylogeny, we associate coding and regulatory variation with olfaction and hibernation. Focusing on biodiversity conservation, we identify genomic metrics that predict species at risk of extinction.
Publisher
Cold Spring Harbor Laboratory