The quantitative genetics of gene expression in Mimulus guttatus

Veltsos, Paris; Kelly, John K.

doi:10.1371/journal.pgen.1011072

Title: The quantitative genetics of gene expression in Mimulus guttatus

Journal Article · 10 April 2024 · PLoS Genetics

DOI: https://doi.org/10.1371/journal.pgen.1011072 · OSTI ID:2469705

^[1];

^[2]

Univ. of Kansas, Lawrence, KS (United States); Vrije Universiteit Brussel (VUB), Brussels (Belgium)
Univ. of Kansas, Lawrence, KS (United States)

Gene expression can be influenced by genetic variants that are closely linked to the expressed gene (cis eQTLs) and variants in other parts of the genome (trans eQTLs). We created a multiparental mapping population by sampling genotypes from a single natural population of Mimulus guttatus and scored gene expression in the leaves of 1,588 plants. We find that nearly every measured gene exhibits cis regulatory variation (91% have FDR < 0.05). cis eQTLs are usually allelic series with three or more functionally distinct alleles. The cis locus explains about two thirds of the standing genetic variance (on average) but varies among genes and tends to be greatest when there is high indel variation in the upstream regulatory region and high nucleotide diversity in the coding sequence. Despite mapping over 10,000 trans eQTL / affected gene pairs, most of the genetic variance generated by trans acting loci remains unexplained. This implies a large reservoir of trans acting genes with subtle or diffuse effects. Mapped trans eQTLs show lower allelic diversity but much higher genetic dominance than cis eQTLs. Several analyses also indicate that trans eQTLs make a substantial contribution to the genetic correlations in expression among different genes. They may thus be essential determinants of “gene expression modules,” which has important implications for the evolution of gene expression and how it is studied by geneticists.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2469705

Journal Information:: PLoS Genetics, Journal Name: PLoS Genetics Journal Issue: 4 Vol. 20; ISSN 1553-7404

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (72)

The genomic scale of fluctuating selection in a natural plant population Kelly, John K. Evolution Letters, Vol. 6, Issue 6 https://doi.org/10.1002/evl3.308	journal	December 2022
The investigation of linkage between a quantitative trait and a marker locus Haseman, J. K.; Elston, R. C. Behavior Genetics, Vol. 2, Issue 1 https://doi.org/10.1007/BF01066731	journal	March 1972
The relative importance of principal and modifying genes in determining some human diseases Haldane, J. B. S. Journal of Genetics, Vol. 41, Issue 2-3 https://doi.org/10.1007/BF02983018	journal	January 1941
Descent measures for two loci with some applications Cockerham, C. Clark; Weir, B. S. Theoretical Population Biology, Vol. 4, Issue 3 https://doi.org/10.1016/0040-5809(73)90013-0	journal	September 1973
An Expanded View of Complex Traits: From Polygenic to Omnigenic Boyle, Evan A.; Li, Yang I.; Pritchard, Jonathan K. Cell, Vol. 169, Issue 7 https://doi.org/10.1016/j.cell.2017.05.038	journal	June 2017
Trans Effects on Gene Expression Can Drive Omnigenic Inheritance Liu, Xuanyao; Li, Yang I.; Pritchard, Jonathan K. Cell, Vol. 177, Issue 4 https://doi.org/10.1016/j.cell.2019.04.014	journal	May 2019
The Evolution of Gene Expression in cis and trans Signor, Sarah A.; Nuzhdin, Sergey V. Trends in Genetics, Vol. 34, Issue 7 https://doi.org/10.1016/j.tig.2018.03.007	journal	July 2018
Evolution of amphimixis and recombination under fluctuating selection in one and many traits Kondrashov, Alexey S.; Yampolsky, Lev Yu. Genetical Research, Vol. 68, Issue 2 https://doi.org/10.1017/S0016672300034054	journal	October 1996
Partial self-fertilization and inbreeding depression in two populations of Mimulus guttatus Willis, John H. Heredity, Vol. 71, Issue 2 https://doi.org/10.1038/hdy.1993.118	journal	August 1993
Evolutionary changes in cis and trans gene regulation Wittkopp, Patricia J.; Haerum, Belinda K.; Clark, Andrew G. Nature, Vol. 430, Issue 6995 https://doi.org/10.1038/nature02698	journal	July 2004
Non-adaptive plasticity potentiates rapid adaptive evolution of gene expression in nature Ghalambor, Cameron K.; Hoke, Kim L.; Ruell, Emily W. Nature, Vol. 525, Issue 7569 https://doi.org/10.1038/nature15256	journal	September 2015
Dysregulation of expression correlates with rare-allele burden and fitness loss in maize Kremling, Karl A. G.; Chen, Shu-Yun; Su, Mei-Hsiu Nature, Vol. 555, Issue 7697 https://doi.org/10.1038/nature25966	journal	March 2018
Genome-wide efficient mixed-model analysis for association studies Zhou, Xiang; Stephens, Matthew Nature Genetics, Vol. 44, Issue 7 https://doi.org/10.1038/ng.2310	journal	June 2012
Advantages and pitfalls in the application of mixed-model association methods Yang, Jian; Zaitlen, Noah A.; Goddard, Michael E. Nature Genetics, Vol. 46, Issue 2 https://doi.org/10.1038/ng.2876	journal	January 2014
Genome-wide genetic association of complex traits in heterogeneous stock mice Valdar, William; Solberg, Leah C.; Gauguier, Dominique Nature Genetics, Vol. 38, Issue 8 https://doi.org/10.1038/ng1840	journal	July 2006
Salmon provides fast and bias-aware quantification of transcript expression Patro, Rob; Duggal, Geet; Love, Michael I. Nature Methods, Vol. 14, Issue 4 https://doi.org/10.1038/nmeth.4197	journal	March 2017
RNA-Seq: a revolutionary tool for transcriptomics Wang, Zhong; Gerstein, Mark; Snyder, Michael Nature Reviews Genetics, Vol. 10, Issue 1 https://doi.org/10.1038/nrg2484	journal	January 2009
A comprehensive evaluation of module detection methods for gene expression data Saelens, Wouter; Cannoodt, Robrecht; Saeys, Yvan Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-03424-4	journal	March 2018
Structural variants exhibit widespread allelic heterogeneity and shape variation in complex traits Chakraborty, Mahul; Emerson, J. J.; Macdonald, Stuart J. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12884-1	journal	October 2019
Array programming with NumPy Harris, Charles R.; Millman, K. Jarrod; van der Walt, Stéfan J. Nature, Vol. 585, Issue 7825 https://doi.org/10.1038/s41586-020-2649-2	journal	September 2020
The distribution of individual inbreeding coefficients and pairwise relatedness in a population of Mimulus guttatus Sweigart, Andrea; Karoly, Keith; Jones, Albyn Heredity, Vol. 83, Issue 5 https://doi.org/10.1038/sj.hdy.6886020	journal	November 1999
Dominance and the evolutionary accumulation of cis- and trans-effects on gene expression Lemos, B.; Araripe, L. O.; Fontanillas, P. Proceedings of the National Academy of Sciences, Vol. 105, Issue 38 https://doi.org/10.1073/pnas.0805160105	journal	September 2008
Association mapping reveals the role of purifying selection in the maintenance of genomic variation in gene expression Josephs, Emily B.; Lee, Young Wha; Stinchcombe, John R. Proceedings of the National Academy of Sciences, Vol. 112, Issue 50 https://doi.org/10.1073/pnas.1503027112	journal	November 2015
The Phenome-Wide Distribution of Genetic Variance Blows, Mark W.; Allen, Scott L.; Collet, Julie M. The American Naturalist, Vol. 186, Issue 1 https://doi.org/10.1086/681645	journal	July 2015
Identifying and removing haplotypic duplication in primary genome assemblies Guan, Dengfeng; McCarthy, Shane A.; Wood, Jonathan Bioinformatics, Vol. 36, Issue 9 https://doi.org/10.1093/bioinformatics/btaa025	journal	January 2020
Liftoff: accurate mapping of gene annotations Shumate, Alaina; Salzberg, Steven L. Bioinformatics, Vol. 37, Issue 12 https://doi.org/10.1093/bioinformatics/btaa1016	journal	May 2021
R/qtl: QTL mapping in experimental crosses Broman, K. W.; Wu, H.; Sen, S. Bioinformatics, Vol. 19, Issue 7 https://doi.org/10.1093/bioinformatics/btg112	journal	May 2003
Trimmomatic: a flexible trimmer for Illumina sequence data Bolger, Anthony M.; Lohse, Marc; Usadel, Bjoern Bioinformatics, Vol. 30, Issue 15 https://doi.org/10.1093/bioinformatics/btu170	journal	April 2014
BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs Simão, Felipe A.; Waterhouse, Robert M.; Ioannidis, Panagiotis Bioinformatics, Vol. 31, Issue 19 https://doi.org/10.1093/bioinformatics/btv351	journal	June 2015
The Number of Alleles that can be Maintained in a Finite Population Kimura, Motoo; Crow, James F. Genetics, Vol. 49, Issue 4 https://doi.org/10.1093/genetics/49.4.725	journal	April 1964
Genome-wide association mapping of transcriptome variation inMimulus guttatusindicates differing patterns of selection oncis- versustrans-acting mutations Brown, Keely E.; Kelly, John K. Genetics, Vol. 220, Issue 1 https://doi.org/10.1093/genetics/iyab189	journal	November 2021
The Evolutionary Forces Shaping Cis- and Trans-Regulation of Gene Expression within a Population of Outcrossing Plants Josephs, Emily B.; Lee, Young Wha; Wood, Corlett W. Molecular Biology and Evolution, Vol. 37, Issue 8 https://doi.org/10.1093/molbev/msaa102	journal	April 2020
Natural Variation in Abiotic Stress Responsive Gene Expression and Local Adaptation to Climate in Arabidopsis thaliana Lasky, Jesse R.; Des Marais, David L.; Lowry, David B. Molecular Biology and Evolution, Vol. 31, Issue 9 https://doi.org/10.1093/molbev/msu170	journal	May 2014
The genome portal of the Department of Energy Joint Genome Institute: 2014 updates Nordberg, Henrik; Cantor, Michael; Dusheyko, Serge Nucleic Acids Research, Vol. 42, Issue D1 https://doi.org/10.1093/nar/gkt1069	journal	November 2013
Evolution and Selection of Quantitative Traits Walsh, Bruce; Lynch, Michael Oxford Scholarship Online https://doi.org/10.1093/oso/9780198830870.001.0001	book	July 2018
Integrating genomics and multivariate evolutionary quantitative genetics: a case study of constraints on sexual selection in Drosophila serrata Reddiex, Adam J.; Chenoweth, Stephen F. Proceedings of the Royal Society B: Biological Sciences, Vol. 288, Issue 1960 https://doi.org/10.1098/rspb.2021.1785	journal	October 2021
Multiplexed shotgun genotyping for rapid and efficient genetic mapping Andolfatto, P.; Davison, D.; Erezyilmaz, D. Genome Research, Vol. 21, Issue 4 https://doi.org/10.1101/gr.115402.110	journal	January 2011
Canu: scalable and accurate long-read assembly via adaptive k -mer weighting and repeat separation Koren, Sergey; Walenz, Brian P.; Berlin, Konstantin Genome Research, Vol. 27, Issue 5 https://doi.org/10.1101/gr.215087.116	journal	March 2017
Expression Quantitative Trait Locus Mapping across Water Availability Environments Reveals Contrasting Associations with Genomic Features in Arabidopsis Lowry, David B.; Logan, Tierney L.; Santuari, Luca The Plant Cell, Vol. 25, Issue 9 https://doi.org/10.1105/tpc.113.115352	journal	September 2013
Severe inbreeding depression is predicted by the “rare allele load” inMimulus guttatus* Brown, Keely E.; Kelly, John K. Evolution, Vol. 74, Issue 3 https://doi.org/10.1111/evo.13876	journal	November 2019
Divergent Selection on Flowering time Contributes to Local Adaptation in Mimulus Guttatus Populations Hall, Megan C.; Willis, John H. Evolution, Vol. 60, Issue 12 https://doi.org/10.1111/j.0014-3820.2006.tb01882.x	journal	December 2006
Spatially and temporally varying selection on intrapopulation quantitative trait loci for a life history trade-off inMimulus guttatus Mojica, Julius P.; Lee, Young Wha; Willis, John H. Molecular Ecology, Vol. 21, Issue 15 https://doi.org/10.1111/j.1365-294X.2012.05662.x	journal	June 2012
Contribution of chromosomal polymorphisms to the G‐matrix ofMimulus guttatus Scoville, Alison; Lee, Young Wha; Willis, John H. New Phytologist, Vol. 183, Issue 3 https://doi.org/10.1111/j.1469-8137.2009.02947.x	journal	July 2009
Connecting qtls to the G-Matrix of Evolutionary Quantitative Genetics Kelly, John K. Evolution, Vol. 63, Issue 4 https://doi.org/10.1111/j.1558-5646.2008.00590.x	journal	April 2009
The genetic architecture of local adaptation and reproductive isolation in sympatry within the Mimulus guttatus species complex Ferris, Kathleen G.; Barnett, Laryssa L.; Blackman, Benjamin K. Molecular Ecology, Vol. 26, Issue 1 https://doi.org/10.1111/mec.13763	journal	August 2016
Population structure and local selection yield high genomic variation in Mimulus guttatus Puzey, Joshua R.; Willis, John H.; Kelly, John K. Molecular Ecology, Vol. 26, Issue 2 https://doi.org/10.1111/mec.13922	journal	December 2016
Structure and stability of genetic variance–covariance matrices: A Bayesian sparse factor analysis of transcriptional variation in the three‐spined stickleback Siren, J.; Ovaskainen, O.; Merilä, J. Molecular Ecology, Vol. 26, Issue 19 https://doi.org/10.1111/mec.14265	journal	August 2017
Rapid evolutionary changes in gene expression in response to climate fluctuations Hamann, Elena; Pauli, Christopher S.; Joly‐Lopez, Zoé Molecular Ecology, Vol. 30, Issue 1 https://doi.org/10.1111/mec.15583	journal	August 2020
On the importance of balancing selection in plants Delph, Lynda F.; Kelly, John K. New Phytologist, Vol. 201, Issue 1 https://doi.org/10.1111/nph.12441	journal	August 2013
What can genome‐wide association studies tell us about the evolutionary forces maintaining genetic variation for quantitative traits? Josephs, Emily B.; Stinchcombe, John R.; Wright, Stephen I. New Phytologist, Vol. 214, Issue 1 https://doi.org/10.1111/nph.14410	journal	February 2017
Centromere-Associated Female Meiotic Drive Entails Male Fitness Costs in Monkeyflowers Fishman, Lila; Saunders, Arpiar Science, Vol. 322, Issue 5907 https://doi.org/10.1126/science.1161406	journal	December 2008
The Genetic Architecture of Maize Flowering Time Buckler, E. S.; Holland, J. B.; Bradbury, P. J. Science, Vol. 325, Issue 5941, p. 714-718 https://doi.org/10.1126/science.1174276	journal	August 2009
Paternal Dominance of Trans-eQTL Influences Gene Expression Patterns in Maize Hybrids Swanson-Wagner, R. A.; DeCook, R.; Jia, Y. Science, Vol. 326, Issue 5956 https://doi.org/10.1126/science.1178294	journal	November 2009
Winter storms drive rapid phenotypic, regulatory, and genomic shifts in the green anole lizard Campbell-Staton, Shane C.; Cheviron, Zachary A.; Rochette, Nicholas Science, Vol. 357, Issue 6350 https://doi.org/10.1126/science.aam5512	journal	August 2017
Selective trade-offs maintain alleles underpinning complex trait variation in plants Troth, Ashley; Puzey, Joshua R.; Kim, Rebecca S. Science, Vol. 361, Issue 6401 https://doi.org/10.1126/science.aat5760	journal	August 2018
WGCNA: an R package for weighted correlation network analysis Langfelder, Peter; Horvath, Steve BMC Bioinformatics, Vol. 9, Issue 1 https://doi.org/10.1186/1471-2105-9-559	journal	December 2008
Versatile and open software for comparing large genomes Kurtz, Stefan; Phillippy, Adam; Delcher, Arthur L. Genome Biology, Vol. 5, Issue 2, R12 https://doi.org/10.1186/gb-2004-5-2-r12	journal	January 2004
Mixture modeling of transcript abundance classes in natural populations Hsieh, Wen-Ping; Passador-Gurgel, Gisele; Stone, Eric A. Genome Biology, Vol. 8, Issue 6 https://doi.org/10.1186/gb-2007-8-6-r98	journal	June 2007
voom: precision weights unlock linear model analysis tools for RNA-seq read counts Law, Charity W.; Chen, Yunshun; Shi, Wei Genome Biology, Vol. 15, Issue 2 https://doi.org/10.1186/gb-2014-15-2-r29	journal	January 2014
GOOGA: A platform to synthesize mapping experiments and identify genomic structural diversity Flagel, Lex E.; Blackman, Benjamin K.; Fishman, Lila PLOS Computational Biology, Vol. 15, Issue 4 https://doi.org/10.1371/journal.pcbi.1006949	journal	April 2019
Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings Visscher, Peter M.; Medland, Sarah E.; Ferreira, Manuel A. R. PLoS Genetics, Vol. 2, Issue 3 https://doi.org/10.1371/journal.pgen.0020041	journal	January 2006
A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana Kover, Paula X.; Valdar, William; Trakalo, Joseph PLoS Genetics, Vol. 5, Issue 7 https://doi.org/10.1371/journal.pgen.1000551	journal	July 2009
Genetic Dissection of the Drosophila melanogaster Female Head Transcriptome Reveals Widespread Allelic Heterogeneity King, Elizabeth G.; Sanderson, Brian J.; McNeil, Casey L. PLoS Genetics, Vol. 10, Issue 5 https://doi.org/10.1371/journal.pgen.1004322	journal	May 2014
Gene co-expression network connectivity is an important determinant of selective constraint Mähler, Niklas; Wang, Jing; Terebieniec, Barbara K. PLOS Genetics, Vol. 13, Issue 4 https://doi.org/10.1371/journal.pgen.1006402	journal	April 2017
Predicting evolutionary change at the DNA level in a natural Mimulus population Monnahan, Patrick J.; Colicchio, Jack; Fishman, Lila PLOS Genetics, Vol. 17, Issue 1 https://doi.org/10.1371/journal.pgen.1008945	journal	January 2021
Segregating Variation in the Transcriptome:CisRegulation and Additivity of Effects Hughes, Kimberly A.; Ayroles, Julien F.; Reedy, Melissa M. Genetics, Vol. 173, Issue 3 https://doi.org/10.1534/genetics.105.051474	journal	July 2006
Properties and Power of the Drosophila Synthetic Population Resource for the Routine Dissection of Complex Traits King, Elizabeth G.; Macdonald, Stuart J.; Long, Anthony D. Genetics, Vol. 191, Issue 3 https://doi.org/10.1534/genetics.112.138537	journal	April 2012
A Segregating Inversion Generates Fitness Variation in Yellow Monkeyflower (Mimulus guttatus) Lee, Young Wha; Fishman, Lila; Kelly, John K. Genetics, Vol. 202, Issue 4 https://doi.org/10.1534/genetics.115.183566	journal	February 2016
The Measurement of Selection on Correlated Characters Lande, Russell; Arnold, Stevan J. Evolution, Vol. 37, Issue 6 https://doi.org/10.2307/2408842	journal	November 1983
Adaptive Radiation Along Genetic Lines of Least Resistance Schluter, Dolph Evolution, Vol. 50, Issue 5 https://doi.org/10.2307/2410734	journal	October 1996
Response to Selection in Partially Self-Fertilizing Populations. II. Selection on Multiple Traits Kelly, John K. Evolution, Vol. 53, Issue 2 https://doi.org/10.2307/2640772	journal	April 1999
Novel Traits, Flower Symmetry, and Transcriptional Autoregulation: New Hypotheses From Bioinformatic and Experimental Data Sengupta, Aniket; Hileman, Lena C. Frontiers in Plant Science, Vol. 9 https://doi.org/10.3389/fpls.2018.01561	journal	October 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
alleles
gene expression
gene loci
gene mapping
genetics
genomics
heterozygosity
quantitative trait loci

Title: The quantitative genetics of gene expression in Mimulus guttatus

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