Elucidating the patterns of pleiotropy and its biological relevance in maize

Authors: KHAIPHO-BURCH, MERRITT - Cornell University; FEREBEE, TAYLOR - Cornell University; GIRI, ANJU - Cornell University; RAMSTEIN, GUILLAUME - Aarhuis University; MONIER, BRANDON - Cornell University; YI, EMILY - Cornell University; ROMAY, MARIA CINTA - Cornell University; Buckler, Edward - Ed

Submitted to: PLoS Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/9/2023
Publication Date: 3/21/2023
Citation: Khaipho-Burch, M., Ferebee, T., Giri, A., Ramstein, G., Monier, B., Yi, E., Romay, M., Buckler IV, E.S. 2023. Elucidating the patterns of pleiotropy and its biological relevance in maize. PLoS Genetics. PLoS Genet 19(3): e1010664. https://doi.org/10.1371/journal.pgen.1010664.
DOI: https://doi.org/10.1371/journal.pgen.1010664

Interpretive Summary: Here we investigated the prevalence and biological mechanisms regulating pleiotropy in maize, a phenomenon where a single gene can affect multiple traits. Estimates of pleiotropy in the past have been limited by their genomic resolution, the number of traits under investigation, and statistical models used to analyze their data. Our paper addresses these issues and gained a better understanding of the implications of pleiotropy for breeding and crop improvement. This paper investigated pleiotropy in maize. To do this we analyzed a large dataset of publicly available maize traits and found that pleiotropy is not very common; however, it does vary depending on the type of trait under investigation. Additionally, we identified several genetic and biological factors that play a role in regulating the amount of pleiotropy present. This research helps us understand how genes impact multiple traits in maize, which can be important for improving crops through plant breeding. This study advances our understanding of the genetic architecture of maize by describing the limited nature of pleiotropy. Past studies have typically conflated the amount of pleiotropy present within the maize genome, leading to a false assumption of its importance. Here we challenged the assumption of pervasive pleiotropy with numerous machine-learning models and determined that pleiotropy is determined by the type of trait under investigation. Additionally, our results suggest that many of the known pleiotropic loci described in the past are likely caused by statistical noise imparted by common genetic mapping techniques. Our results can also aid plant breeders in better understanding the maize genome in order to adapt new maize varieties to changing environments, produce higher yields, and be more nutritious.

Technical Abstract: Pleiotropy—when a single gene controls two or more seemingly unrelated traits—has been shown to impact genes with effects on flowering time, leaf architecture, and inflorescence morphology in maize. However, the genome-wide impact of biological pleiotropy across all maize phenotypes is largely unknown. Here, we investigate the extent to which biological pleiotropy impacts phenotypes within maize using GWAS summary statistics reanalyzed from previously published metabolite, field, and expression phenotypes across the Nested Association Mapping population and Goodman Association Panel. Through phenotypic saturation of 120,597 traits, we obtain over 480 million significant quantitative trait nucleotides. We estimate that only 1.56–32.3% of intervals show some degree of pleiotropy. We then assess the relationship between pleiotropy and various biological features such as gene expression, chromatin accessibility, sequence conservation, and enrichment for gene ontology terms. We find very little relationship between pleiotropy and these variables when compared to permuted pleiotropy. We hypothesize that biological pleiotropy of common alleles is not widespread in maize and is highly impacted by nuisance terms such as population structure and linkage disequilibrium. Natural selection on large standing natural variation in maize populations may target wide and large effect variants, leaving the prevalence of detectable pleiotropy relatively low.