An official website of the United States government
The underlying genetic changes that regulate the appearance and disappearance of repeated traits, or serial homologs, remain poorly understood. One hypothesis is that variation in genomic regions flanking master regulatory genes, also known as input–output genes, controls variation in trait number, making the locus of evolution almost predictable. Another hypothesis implicates genetic variation in up- or downstream loci of master control genes. Here, we use the butterfly Bicyclus anynana , a species that exhibits natural variation in eyespot number on the dorsal hindwing, to test these two hypotheses. We first estimated the heritability of dorsal hindwing eyespot number by breeding multiple butterfly families differing in eyespot number and regressing eyespot numbers of offspring on midparent values. We then estimated the number and identity of independent genetic loci contributing to eyespot number variation by performing a genome-wide association study with restriction site-associated DNA sequencing from multiple individuals varying in number of eyespots sampled across a freely breeding laboratory population. We found that dorsal hindwing eyespot number has a moderately high heritability of ∼0.50 and is characterized by a polygenic architecture. Previously identified genomic regions involved in eyespot development, and novel ones, display high association with dorsal hindwing eyespot number, suggesting that homolog number variation is likely determined by regulatory changes at multiple loci that build the trait, and not by variation at single master regulators or input–output genes.
more »
« less
Master regulators of biological systems in higher dimensions
A longstanding goal of biology is to identify the key genes and species that critically impact evolution, ecology, and health. Network analysis has revealed keystone species that regulate ecosystems and master regulators that regulate cellular genetic networks. Yet these studies have focused on pairwise biological interactions, which can be affected by the context of genetic background and other species present, generating higher-order interactions. The important regulators of higher-order interactions are unstudied. To address this, we applied a high-dimensional geometry approach that quantifies epistasis in a fitness landscape to ask how individual genes and species influence the interactions in the rest of the biological network. We then generated and also reanalyzed 5-dimensional datasets (two genetic, two microbiome). We identified key genes (e.g., therbslocus andpykF) and species (e.g.,Lactobacilli) that control the interactions of many other genes and species. These higher-order master regulators can induce or suppress evolutionary and ecological diversification by controlling the topography of the fitness landscape. Thus, we provide a method and mathematical justification for exploration of biological networks in higher dimensions.
more »
« less
- PAR ID:
- 10496385
- Publisher / Repository:
- PNAS
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 120
- Issue:
- 51
- ISSN:
- 0027-8424
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
One of the main drivers of evolution is natural selection, which is when organisms better adapted to their environment are more likely to survive and reproduce. A common metaphor to explain this process is a landscape covered in peaks and valleys: the peaks represent genetic combinations or traits with high evolutionary fitness, while the valleys represent those with low fitness. As a population evolves and its environment changes, it moves among these peaks taking small steps across the landscape. However, there is a limit to how far an organism can travel in one leap. So, what happens when they need to cross a valley of low fitness to get to the next peak? To address this question, Patton et al. studied three young species of pupfish that recently evolved from a common ancestor and co-habit the same environment in the Caribbean. Patton et al. sequenced whole genomes of each new species and used this to build a genotypic fitness landscape, a network linking neighboring genotypes which each have a unique fitness value that was measured during field experiments. This revealed that most of the paths connecting the different species passed through valleys of low fitness. But there were rare, narrow ridges connecting each species. Next, Patton et al. found that new mutations as well as genetic variations that arose from mating with pupfish on other Caribbean islands altered genetic interactions and changed the shape of the fitness landscape. Ultimately, this significantly increased the accessibility of fitness peaks by both adding more ridges and decreasing the lengths of paths, expanding the realm of possible evolutionary outcomes. Understanding how fitness landscapes change during evolution could help to explain where new species come from. Other researchers could apply the same approach to estimate the genotypic fitness landscapes of other species, from bacteria to vertebrates. These networks could be used to visualize the complex fitness landscape that connects all lifeforms on Earth.more » « less
-
The effect of a mutation on the organism often depends on what other mutations are already present in its genome. Geneticists refer to such mutational interactions as epistasis. Pairwise epistatic effects have been recognized for over a century, and their evolutionary implications have received theoretical attention for nearly as long. However, pairwise epistatic interactions themselves can vary with genomic background. This is called higher-order epistasis, and its consequences for evolution are much less well understood. Here, we assess the influence that higher-order epistasis has on the topography of 16 published, biological fitness landscapes. We find that on average, their effects on fitness landscape declines with order, and suggest that notable exceptions to this trend may deserve experimental scrutiny. We conclude by highlighting opportunities for further theoretical and experimental work dissecting the influence that epistasis of all orders has on fitness landscape topography and on the efficiency of evolution by natural selection.more » « less
-
ABSTRACT Necrotrophic pathogens cause serious threats to agricultural crops, and understanding the resistance genes and their genetic networks is key to breeding new plant cultivars with better resistance traits. AlthoughAlternaria alternatacauses black spot in important leafy brassica vegetables, and leads to significant loss of yield and food quality, little is known about plant–A. alternatainteractions. In this study, we used a unique and large collection of single, double and triple mutant lines of defence metabolite regulators inArabidopsisto explore how these transcription factors and their epistatic networks may influenceA. alternatainfections. This identified nine novel regulators and 20 pairs of epistatic interactions that modulateArabidopsisplants' defence responses toA. alternatainfection. We further showed that the glucosinolate 4‐methoxy‐indol‐3‐ylmethyl is the only glucosinolate consistently responsive toA. alternatainfection in Col‐0 ecotype. With the further exploration of the regulators and the genetic networks on modulating the accumulation of glucosinolates underA. alternatainfection, an inverted triangle regulatory model was proposed forArabidopsisplants' defence responses at a metabolic level and a phenotypic level.more » « less
-
Summary Here, we investigated the molecular genetic basis of mite domatia, structures on the underside of leaves that house mutualistic mites, and intraspecific variation in domatia size inVitis riparia(riverbank grape).Domatia and leaf traits were measured, and the transcriptomes of mite domatia from two genotypes ofV. ripariawith distinct domatia sizes were sequenced to investigate the molecular genetic pathways that regulate domatia development and intraspecific variation in domatia traits.Key trichome regulators as well as auxin and jasmonic acid are involved in domatia development. Genes involved in cell wall biosynthesis, biotic interactions, and molecule transport/metabolism are upregulated in domatia, consistent with their role in domatia development and function.This work is one of the first to date that provides insight into the molecular genetic bases of mite domatia. We identified key genetic pathways involved in domatia development and function, and uncovered unexpected pathways that provide an avenue for future investigation. We also found that intraspecific variation in domatia size inV. ripariaseems to be driven by differences in overall leaf development between genotypes.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1073/pnas.2300634120
