Leveraging Massively Parallel Reporter Assays for Evolutionary Questions

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2023 Feb 15

PMID 36788564

Authors

Irene Gallego Romero

Amanda J Lea

Affiliations

Soon will be listed here.

Abstract

A long-standing goal of evolutionary biology is to decode how gene regulation contributes to organismal diversity. Doing so is challenging because it is hard to predict function from non-coding sequence and to perform molecular research with non-model taxa. Massively parallel reporter assays (MPRAs) enable the testing of thousands to millions of sequences for regulatory activity simultaneously. Here, we discuss the execution, advantages, and limitations of MPRAs, with a focus on evolutionary questions. We propose solutions for extending MPRAs to rare taxa and those with limited genomic resources, and we underscore MPRA's broad potential for driving genome-scale, functional studies across organisms.

Citing Articles

Novelty versus innovation of gene regulatory elements in human evolution and disease.

Katikaneni A, Lowe C Curr Opin Genet Dev. 2024; 90:102279.

PMID: 39591813 PMC: 11769741. DOI: 10.1016/j.gde.2024.102279.

Large-scale analysis of the integration of enhancer-enhancer signals by promoters.

Martinez-Ara M, Comoglio F, van Steensel B Elife. 2024; 12.

PMID: 39466837 PMC: 11517252. DOI: 10.7554/eLife.91994.

Translation of genome-wide association study: from genomic signals to biological insights.

Bruner W, Grant S Front Genet. 2024; 15:1375481.

PMID: 39421299 PMC: 11484060. DOI: 10.3389/fgene.2024.1375481.

Decoding biology with massively parallel reporter assays and machine learning.

La Fleur A, Shi Y, Seelig G Genes Dev. 2024; 38(17-20):843-865.

PMID: 39362779 PMC: 11535156. DOI: 10.1101/gad.351800.124.

Massively parallel approaches for characterizing noncoding functional variation in human evolution.

Rong S, Root E, Reilly S Curr Opin Genet Dev. 2024; 88:102256.

PMID: 39217658 PMC: 11648527. DOI: 10.1016/j.gde.2024.102256.

References

Anderson J, Vilgalys T, Tung J . Broadening primate genomics: new insights into the ecology and evolution of primate gene regulation. Curr Opin Genet Dev. 2020; 62:16-22. PMC: 7483836. DOI: 10.1016/j.gde.2020.05.009. View

Housman G, Gilad Y . Prime time for primate functional genomics. Curr Opin Genet Dev. 2020; 62:1-7. PMC: 8170550. DOI: 10.1016/j.gde.2020.04.007. View

Gallego Romero I, Ruvinsky I, Gilad Y . Comparative studies of gene expression and the evolution of gene regulation. Nat Rev Genet. 2012; 13(7):505-16. PMC: 4034676. DOI: 10.1038/nrg3229. View

CARROLL S . Endless forms: the evolution of gene regulation and morphological diversity. Cell. 2000; 101(6):577-80. DOI: 10.1016/s0092-8674(00)80868-5. View

Mack K, Nachman M . Gene Regulation and Speciation. Trends Genet. 2016; 33(1):68-80. PMC: 5182078. DOI: 10.1016/j.tig.2016.11.003. View

Rubinstein M, de Souza F . Evolution of transcriptional enhancers and animal diversity. Philos Trans R Soc Lond B Biol Sci. 2013; 368(1632):20130017. PMC: 3826491. DOI: 10.1098/rstb.2013.0017. View

Pennacchio L, Bickmore W, Dean A, Nobrega M, Bejerano G . Enhancers: five essential questions. Nat Rev Genet. 2013; 14(4):288-95. PMC: 4445073. DOI: 10.1038/nrg3458. View

Long H, Prescott S, Wysocka J . Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution. Cell. 2016; 167(5):1170-1187. PMC: 5123704. DOI: 10.1016/j.cell.2016.09.018. View

Ong C, Corces V . Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat Rev Genet. 2011; 12(4):283-93. PMC: 3175006. DOI: 10.1038/nrg2957. View

10.

Maston G, Evans S, Green M . Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet. 2006; 7:29-59. DOI: 10.1146/annurev.genom.7.080505.115623. View

11.

Pacis A, Mailhot-Leonard F, Tailleux L, Randolph H, Yotova V, Dumaine A . Gene activation precedes DNA demethylation in response to infection in human dendritic cells. Proc Natl Acad Sci U S A. 2019; 116(14):6938-6943. PMC: 6452747. DOI: 10.1073/pnas.1814700116. View

12.

Carroll S . Evolution at two levels: on genes and form. PLoS Biol. 2005; 3(7):e245. PMC: 1174822. DOI: 10.1371/journal.pbio.0030245. View

13.

Wray G . The evolutionary significance of cis-regulatory mutations. Nat Rev Genet. 2007; 8(3):206-16. DOI: 10.1038/nrg2063. View

14.

Rebeiz M, Tsiantis M . Enhancer evolution and the origins of morphological novelty. Curr Opin Genet Dev. 2017; 45:115-123. PMC: 5623808. DOI: 10.1016/j.gde.2017.04.006. View

15.

Chan Y, Marks M, Jones F, Villarreal Jr G, Shapiro M, Brady S . Adaptive evolution of pelvic reduction in sticklebacks by recurrent deletion of a Pitx1 enhancer. Science. 2009; 327(5963):302-5. PMC: 3109066. DOI: 10.1126/science.1182213. View

16.

Capra J, Erwin G, Mckinsey G, Rubenstein J, Pollard K . Many human accelerated regions are developmental enhancers. Philos Trans R Soc Lond B Biol Sci. 2013; 368(1632):20130025. PMC: 3826498. DOI: 10.1098/rstb.2013.0025. View

17.

Moon J, Capra J, Abbot P, Rokas A . Signatures of Recent Positive Selection in Enhancers Across 41 Human Tissues. G3 (Bethesda). 2019; 9(8):2761-2774. PMC: 6686946. DOI: 10.1534/g3.119.400186. View

18.

Sholtis S, Noonan J . Gene regulation and the origins of human biological uniqueness. Trends Genet. 2010; 26(3):110-8. DOI: 10.1016/j.tig.2009.12.009. View

19.

Colbran L, Chen L, Capra J . Sequence Characteristics Distinguish Transcribed Enhancers from Promoters and Predict Their Breadth of Activity. Genetics. 2019; 211(4):1205-1217. PMC: 6456323. DOI: 10.1534/genetics.118.301895. View

20.

Zeng X, Park S, Nakai K . Characterizing Promoter and Enhancer Sequences by a Deep Learning Method. Front Genet. 2021; 12:681259. PMC: 8239401. DOI: 10.3389/fgene.2021.681259. View