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Record W4367173653 · doi:10.1126/science.abn3943

Evolutionary constraint and innovation across hundreds of placental mammals

2023· article· en· W4367173653 on OpenAlex
Matthew J. Christmas, Irene M. Kaplow, Diane P. Genereux, Patrick F. Sullivan, Allyson G. Hindle, Matteo Bianchi, Ana M. Breit, Mark Diekhans, Cornelia Fanter, Nicole M. Foley, Daniel B. Goodman, Linda Goodman, Bogdan Kirilenko, Abigail Lind, Jennifer R. S. Meadows, Ruby Redlich, Louise Ryan, Ross Swofford, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Ashley R. Brown, Joana Damas, Kaili Fan, John Gatesy, Jenna Grimshaw, Jeremy Johnson, Alyssa J. Lawler, Voichita D. Marinescu, Kathleen M. Morrill, Austin Osmanski, BaDoi N. Phan, Steven K. Reilly, Daniel E. Schäffer, Cynthia Steiner, Megan A. Supple, Aryn P. Wilder, Morgan Wirthlin, James R. Xue, Susan J. Birren, Steven Gazal, Tomàs Marquès‐Bonet, Wynn K. Meyer, Martin Nweeia, Pardis C. Sabeti, Beth Shapiro, Arian F. A. Smit, Mark S. Springer, Emma C. Teeling, Zhiping Weng, Michael Hiller, Danielle L. Levesque, Harris A. Lewin, William J. Murphy, Arcadi Navarro, Benedict Paten, Katherine S. Pollard, David A. Ray, Irina Ruf, Oliver A. Ryder, Andreas R. Pfenning, Kerstin Lindblad‐Toh, Kevin R. Bredemeyer, Hiram Clawson, Federica Di Palma, Eduardo Eizirik, Karin Forsberg‐Nilsson, Carlos J. Garcia, Michaela K. Halsey, Andrew J. Harris, Glenn Hickey, David Juan, Jennifer M. Korstian, Thomas Lehmann, Ava Mackay-Smith, Victor C. Mason, Jill E. Moore, Diana D. Moreno-Santillán, Gerard Muntané, Sylvia Ortmann, Henry Pratt, Jeb Rosen, Aitor Serres, Chaitanya Srinivasan, Jessica M. Storer, Kevin A. Sullivan, Elisabeth Sundström, Joy-El Talbot, Jason Turner-Maier, Chao Wang, Juehan Wang, Xiaomeng Zhang

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueScience · 2023
Typearticle
Languageen
FieldEarth and Planetary Sciences
TopicEvolution and Paleontology Studies
Canadian institutionsCanadian Museum of Nature
FundersNational Human Genome Research InstituteAgencia Estatal de InvestigaciónVetenskapsrådetUniversity of California, DavisNational Science FoundationScience Foundation IrelandScience for Life LaboratoryUppsala Multidisciplinary Center for Advanced Computational ScienceIrish Research CouncilHigh Performance Research Computing, Texas A and M UniversityUniversity of MaineUniversity College DublinEuropean CommissionBroad InstituteRoddenberry FoundationCarnegie Mellon UniversityGladstone InstitutesNational Cancer InstituteKnut och Alice Wallenbergs StiftelseLehigh UniversityAlfred P. Sloan FoundationNational Institutes of HealthNational Institute on AgingNational Institute on Drug Abuse
KeywordsConstraint (computer-aided design)Evolutionary biologyBiologyBiological evolutionComputational biologyGeneticsMathematics

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.723

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.035
GPT teacher head0.298
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it