A compendium of human gene functions derived from evolutionary modelling

M Marc Feuermann H Huaiyu Mi P Pascale Gaudet A Anushya Muruganujan S Suzanna E. Lewis D Dustin Ebert T Tremayne Mushayahama S Suzanne A. Aleksander J James Balhoff S Seth Carbon J J. Michael Cherry H Harold J. Drabkin N Nomi L. Harris D David P. Hill R Raymond Lee C Colin Logie S Sierra Moxon C Christopher J. Mungall P Paul W. Sternberg K Kimberly Van Auken J Jolene Ramsey D Deborah A. Siegele R Rex L. Chisholm P Petra Fey M Michelle Giglio S Suvarna Nadendla G Giulia Antonazzo H Helen Attrill N Nicholas H. Brown P Phani V. Garapati S Steven Marygold S Saadullah H. Ahmed P Praoparn Asanitthong D Diana Luna Buitrago M Meltem N. Erdol M Matthew C. Gage S Siyao Huang M Mohamed Ali Kadhum K Kan Yan Chloe Li M Miao Long A Aleksandra Michalak A Angeline Pesala A Armalya Pritazahra S Shirin C. C. Saverimuttu R Renzhi Su Q Qianhan Xu R Ruth C. Lovering J Judith Blake K Karen Christie L Lori Corbani M Mary E. Dolan L Li Ni D Dmitry Sitnikov C Cynthia Smith M Manuel Lera-Ramirez K Kim Rutherford V Valerie Wood P Peter D’Eustachio W Wendy M. Demos J Jeffrey L. De Pons M Melinda R. Dwinell G G. Thomas Hayman M Mary L. Kaldunski A Anne E. Kwitek S Stanley J. F. Laulederkind J Jennifer R. Smith M Marek A. Tutaj M Mahima Vedi S Shur-Jen Wang S Stacia R. Engel K Kalpana Karra S Stuart R. Miyasato R Robert S. Nash M Marek S. Skrzypek S Shuai Weng E Edith D. Wong T Tilmann Achsel M Maria Andres-Alonso C Claudia Bagni Àlex Bayés T Thomas Biederer N Nils Brose J John Jia En Chua M Marcelo P. Coba L L. Niels Cornelisse J Jaime de Juan-Sanz H Hana L. Goldschmidt E Eckart D. Gundelfinger R Richard L. Huganir C Cordelia Imig R Reinhard Jahn H Hwajin Jung P Pascal S. Kaeser E Eunjoon Kim F Frank Koopmans M Michael R. Kreutz N Noa Lipstein H Harold D. MacGillavry P Peter S. McPherson V Vincent O’Connor R Rainer Pielot T Timothy A. Ryan C Carlo Sala M Morgan Sheng K Karl-Heinz Smalla A A. B. Smit R Ruud F. Toonen J Jan R. T. van Weering M Matthijs Verhage C Chiara Verpelli E Erika Bakker T Tanya Z. Berardini L Leonore Reiser A Andrea Auchincloss K Kristian Axelsen G Ghislaine Argoud-Puy M Marie-Claude Blatter E Emmanuel Boutet L Lionel Breuza A Alan Bridge C Cristina Casals-Casas E Elisabeth Coudert A Anne Estreicher M Maria Livia Famiglietti A Arnaud Gos N Nadine Gruaz-Gumowski C Chantal Hulo N Nevila Hyka-Nouspikel F Florence Jungo P Philippe Le Mercier D Damien Lieberherr P Patrick Masson A Anne Morgat I Ivo Pedruzzi L Lucille Pourcel S Sylvain Poux C Catherine Rivoire S Shyamala Sundaram E Emily Bowler-Barnett H Hema Bye-A-Jee P Paul Denny A Alexandr Ignatchenko R Rizwan Ishtiaq A Antonia Lock Y Yvonne Lussi M Michele Magrane M Maria J. Martin S Sandra Orchard P Pedro Raposo E Elena Speretta N Nidhi Tyagi K Kate Warner R Rossana Zaru J Juancarlos Chan S Stavros Diamantakis D Daniela Raciti M Malcolm Fisher C Christina James-Zorn V Virgilio Ponferrada A Aaron Zorn S Sridhar Ramachandran L Leyla Ruzicka M Monte Westerfield P Paul D. Thomas

Abstract

Abstract A comprehensive, computable representation of the functional repertoire of all macromolecules encoded within the human genome is a foundational resource for biology and biomedical research. The Gene Ontology Consortium has been working towards this goal by generating a structured body of information about gene functions, which now includes experimental findings reported in more than 175,000 publications for human genes and genes in experimentally tractable model organisms1,2. Here, we describe the results of a large, international effort to integrate all of these findings to create a representation of human gene functions that is as complete and accurate as possible. Specifically, we apply an expert-curated, explicit evolutionary modelling approach to all human protein-coding genes. This approach integrates available experimental information across families of related genes into models that reconstruct the gain and loss of functional characteristics over evolutionary time. The models and the resulting set of 68,667 integrated gene functions cover approximately 82% of human protein-coding genes. The functional repertoire reveals a marked preponderance of molecular regulatory functions, and the models provide insights into the evolutionary origins of human gene functions. We show that our set of descriptions of functions can improve the widely used genomic technique of Gene Ontology enrichment analysis. The experimental evidence for each functional characteristic is recorded, thereby enabling the scientific community to help review and improve the resource, which we have made publicly available.

Article Details

Journal Nature
Volume / Issue Vol. 640, Issue 8057
Published April 03, 2025
Pages 146-154
ISSN 0028-0836
Publisher Nature Portfolio

Journal Info

Nature

Nature Portfolio

ISSN: 0028-0836 Health Sciences

Authors (164)

M

Marc Feuermann

H

Huaiyu Mi

P

Pascale Gaudet

A

Anushya Muruganujan

S

Suzanna E. Lewis

D

Dustin Ebert

T

Tremayne Mushayahama

S

Suzanne A. Aleksander

J

James Balhoff

S

Seth Carbon

J

J. Michael Cherry

H

Harold J. Drabkin

N

Nomi L. Harris

D

David P. Hill

R

Raymond Lee

C

Colin Logie

S

Sierra Moxon

C

Christopher J. Mungall

P

Paul W. Sternberg

K

Kimberly Van Auken

J

Jolene Ramsey

D

Deborah A. Siegele

R

Rex L. Chisholm

P

Petra Fey

M

Michelle Giglio

S

Suvarna Nadendla

G

Giulia Antonazzo

H

Helen Attrill

N

Nicholas H. Brown

P

Phani V. Garapati

S

Steven Marygold

S

Saadullah H. Ahmed

P

Praoparn Asanitthong

D

Diana Luna Buitrago

M

Meltem N. Erdol

M

Matthew C. Gage

S

Siyao Huang

M

Mohamed Ali Kadhum

K

Kan Yan Chloe Li

M

Miao Long

A

Aleksandra Michalak

A

Angeline Pesala

A

Armalya Pritazahra

S

Shirin C. C. Saverimuttu

R

Renzhi Su

Q

Qianhan Xu

R

Ruth C. Lovering

J

Judith Blake

K

Karen Christie

L

Lori Corbani

M

Mary E. Dolan

L

Li Ni

D

Dmitry Sitnikov

C

Cynthia Smith

M

Manuel Lera-Ramirez

K

Kim Rutherford

V

Valerie Wood

P

Peter D’Eustachio

W

Wendy M. Demos

J

Jeffrey L. De Pons

M

Melinda R. Dwinell

G

G. Thomas Hayman

M

Mary L. Kaldunski

A

Anne E. Kwitek

S

Stanley J. F. Laulederkind

J

Jennifer R. Smith

M

Marek A. Tutaj

M

Mahima Vedi

S

Shur-Jen Wang

S

Stacia R. Engel

K

Kalpana Karra

S

Stuart R. Miyasato

R

Robert S. Nash

M

Marek S. Skrzypek

S

Shuai Weng

E

Edith D. Wong

T

Tilmann Achsel

M

Maria Andres-Alonso

C

Claudia Bagni

Àlex Bayés

T

Thomas Biederer

N

Nils Brose

J

John Jia En Chua

M

Marcelo P. Coba

L

L. Niels Cornelisse

J

Jaime de Juan-Sanz

H

Hana L. Goldschmidt

E

Eckart D. Gundelfinger

R

Richard L. Huganir

C

Cordelia Imig

R

Reinhard Jahn

H

Hwajin Jung

P

Pascal S. Kaeser

E

Eunjoon Kim

F

Frank Koopmans

M

Michael R. Kreutz

N

Noa Lipstein

H

Harold D. MacGillavry

P

Peter S. McPherson

V

Vincent O’Connor

R

Rainer Pielot

T

Timothy A. Ryan

C

Carlo Sala

M

Morgan Sheng

K

Karl-Heinz Smalla

A

A. B. Smit

R

Ruud F. Toonen

J

Jan R. T. van Weering

M

Matthijs Verhage

C

Chiara Verpelli

E

Erika Bakker

T

Tanya Z. Berardini

L

Leonore Reiser

A

Andrea Auchincloss

K

Kristian Axelsen

G

Ghislaine Argoud-Puy

M

Marie-Claude Blatter

E

Emmanuel Boutet

L

Lionel Breuza

A

Alan Bridge

C

Cristina Casals-Casas

E

Elisabeth Coudert

A

Anne Estreicher

M

Maria Livia Famiglietti

A

Arnaud Gos

N

Nadine Gruaz-Gumowski

C

Chantal Hulo

N

Nevila Hyka-Nouspikel

F

Florence Jungo

P

Philippe Le Mercier

D

Damien Lieberherr

P

Patrick Masson

A

Anne Morgat

I

Ivo Pedruzzi

L

Lucille Pourcel

S

Sylvain Poux

C

Catherine Rivoire

S

Shyamala Sundaram

E

Emily Bowler-Barnett

H

Hema Bye-A-Jee

P

Paul Denny

A

Alexandr Ignatchenko

R

Rizwan Ishtiaq

A

Antonia Lock

Y

Yvonne Lussi

M

Michele Magrane

M

Maria J. Martin

S

Sandra Orchard

P

Pedro Raposo

E

Elena Speretta

N

Nidhi Tyagi

K

Kate Warner

R

Rossana Zaru

J

Juancarlos Chan

S

Stavros Diamantakis

D

Daniela Raciti

M

Malcolm Fisher

C

Christina James-Zorn

V

Virgilio Ponferrada

A

Aaron Zorn

S

Sridhar Ramachandran

L

Leyla Ruzicka

M

Monte Westerfield

P

Paul D. Thomas