Predictive Models of Genetic Redundancy in Arabidopsis thaliana

Abstract

Genetic redundancy refers to a situation where an individual with a loss-of-function mutation in one gene (single mutant) does not show an apparent phenotype until one or more paralogs are also knocked out (double/higher-order mutant). Previous studies have identified some characteristics common among redundant gene pairs, but a predictive model of genetic redundancy incorporating a wide variety of features derived from accumulating omics and mutant phenotype data is yet to be established. In addition, the relative importance of these features for genetic redundancy remains largely unclear. Here, we establish machine learning models for predicting whether a gene pair is likely redundant or not in the model plant Arabidopsis thaliana based on six feature categories: functional annotations, evolutionary conservation including duplication patterns and mechanisms, epigenetic marks, protein properties including post-translational modifications, gene expression, and gene network properties. The definition of redundancy, data transformations, feature subsets, and machine learning algorithms used significantly affected model performance based on hold-out, testing phenotype data. Among the most important features in predicting gene pairs as redundant were having a paralog(s) from recent duplication events, annotation as a transcription factor, downregulation during stress conditions, and having similar expression patterns under stress conditions. We also explored the potential reasons underlying mispredictions and limitations of our studies. This genetic redundancy model sheds light on characteristics that may contribute to long-term maintenance of paralogs, and will ultimately allow for more targeted generation of functionally informative double mutants, advancing functional genomic studies.

Understanding redundancy and resilience

“…As we gather more fitness data in plants and initiate a similar modelling study in yeast, it becomes clear that what we learned from the multiple definitions capture overlapping but distinct properties compared to defining genetic redundancy based on fitness". Having established a successful model in plants and yeast (Cusack et al, 2021), Shiu's aim is now to extend it to animals where gene duplication events are considerably rarer. "A key component determining the degree of redundancy is history of recent duplication", he added.…”

“…Having established a successful model in plants and yeast (Cusack et al , 2021), Shiu’s aim is now to extend it to animals where gene duplication events are considerably rarer. “A key component determining the degree of redundancy is history of recent duplication”, he added.…”

Solanum lycopersicum, a Model Plant for the Studies in Developmental Biology, Stress Biology and Food Science

“…Functional redundancy of gene families is always caused by gene duplications and gene family expansion, resulting in so-termed phenotypic robustness [ 18 ]. However, how such phenotypic robustness is maintained in the specific cellular contexts is still seldom studied in plants.…”

Heterotypic transcriptional condensates formed by prion-like paralogous proteins canalize flowering transition in tomato

“…Flowering plants have developed genetic circuitry that buffers against genetic and/or abiotic perturbations to avoid drastic morphological consequences. This type of canalization mechanisms not only maintain the robustness of core developmental programs to preserve phenotypes shaped by long history of natural selection, but also retain the flexibility for phenotypic innovation [ 3 , 4 ]. Not surprisingly, in flowering plants, flowering time and inflorescence architecture, which convey reproductive success, are heavily canalized and show great robustness.…”

“…Not surprisingly, in flowering plants, flowering time and inflorescence architecture, which convey reproductive success, are heavily canalized and show great robustness. Functional redundancy following gene duplications and gene family expansion are commonly hypothesized to underlie phenotypic robustness [ 3 ]. However, exactly how phenotypic robustness is maintained in the context of duplicated genes’ fates is rarely studied and illustrated in plants.…”