Evolutionary constraint and innovation across hundreds of placental mammals.

Christmas MJ, Kaplow IM, Genereux DP, Dong MX, Hughes GM, Li X, Sullivan PF, Hindle AG, Andrews G, Armstrong JC, Bianchi M, Breit AM, Diekhans M, Fanter C, Foley NM, Goodman DB, Goodman L, Keough KC, Kirilenko B, Kowalczyk A, Lawless C, Lind AL, Meadows JRS, Moreira LR, Redlich RW, Ryan L, Swofford R, Valenzuela A, Wagner F, Wallerman O, Brown AR, Damas J, Fan K, Gatesy J, Grimshaw J, Johnson J, Kozyrev SV, Lawler AJ, Marinescu VD, Morrill KM, Osmanski A, Paulat NS, Phan BN, Reilly SK, Schäffer DE, Steiner C, Supple MA, Wilder AP, Wirthlin ME, Xue JR, Zoonomia Consortium§ , Birren BW, Gazal S, Hubley RM, Koepfli K, Marques-Bonet T, Meyer WK, Nweeia M, Sabeti PC, Shapiro B, Smit AFA, Springer MS, Teeling EC, Weng Z, Hiller M, Levesque DL, Lewin HA, Murphy WJ, Navarro A, Paten B, Pollard KS, Ray DA, Ruf I, Ryder OA, Pfenning AR, Lindblad-Toh K, Karlsson EK

Science 380 (6643) eabn3943 [2023-04-28; online 2023-04-28]

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

Bioinformatics Support for Computational Resources [Service]

NGI Short read [Service]

NGI Uppsala (SNP&SEQ Technology Platform) [Service]

National Genomics Infrastructure [Service]

PubMed 37104599

DOI 10.1126/science.abn3943

Crossref 10.1126/science.abn3943

mid: NIHMS1896905
pmc: PMC10250106

Publications 9.5.0