Biology subjects

Munasinghe, M.

Publications and source records attributed to Munasinghe, M..

10 recordsLinked to original sources

bioRxiv2026

Promoter Structural Variants are Drivers of Genome-Wide Differential Expression in Maize

BackgroundStructural variants (SVs) are large insertions or deletions of DNA sequences. While less numerous than single nucleotide polymorphisms, SVs often account for a greater proportion of nucleotide differences between genomes. Their size and frequent association with repetitive sequences has historically hindered their detection, which has limited the ability to associate this variation with molecular and phenotypic trait variation. While some SVs have been linked to observable traits, it remains unclear whether such effects are rare or broadly distributed across the genome. ResultsTo test for genome-wide relationships between SVs and gene expression, we analyzed genome assemblies and transcriptomic data from 10 tissues across 26 diverse maize inbred lines. We identified SVs amongst these lines and examined variants located within the 1kb promoter region upstream of genes. Thousands of genes showed expression differences associated with promoter SVs, often in a tissue-specific manner. One common feature of these SVs was the presence of transposable element sequences. LTR retrotransposons were enriched amongst promoter SVs associated with differential expression and often reduced expression of the nearby gene. Despite widespread expression changes, we found no enrichment for specific biological functions or pathways among affected genes. ConclusionsOur findings indicate that extant TE-mediated promoter SVs play a significant role in shaping gene expression patterns across the maize genome. However, their phenotypic effects appear limited or context-dependent, suggesting that many variants may have minimal impact outside specific developmental stages or environmental conditions.

genomics↗

bioRxiv2025

Genome-wide selection on transposable elements in maize

While most evolutionary research has focused on single nucleotide polymorphisms (SNPs), transposable elements (TEs) represent a major but understudied source of mutations that can influence organismal fitness. Previous studies on TEs often overlook the mechanisms and rates of transposition, rely on short-read sequencing that limits TE detection, or focus on small genomes such as Arabidopsis or Drosophila. In this study, we leveraged high-quality, long-read genome assemblies from 26 maize inbreds to investigate natural selection on TEs. We developed a novel and interpretable method, {Phi}SFS, which incorporates TE age and improves resolution for detecting selection. Using this approach, we identified key factors influencing selection on TEs: (1) the distance to the nearest gene, (2) the pre-insertion DNA methylation level at the insertion site, and (3) intrinsic TE characteristics, including copy number and expression level. This work represents the first application of long-read genome assemblies to study TE selection in a major crop species with a typical plant genome size. Our {Phi}SFSmethod offers a broadly applicable framework for detecting selection on TEs, and the factors uncovered provide new insights into the evolutionary dynamics and trade-offs between TEs and host genes.

evolutionary biology↗

bioRxiv2025

SWIF-TE: identifying novel transposable element insertions from short read data

Transposable element (TE) insertion polymorphisms (TIPs) are TEs not in the same location between individuals. TIPs have contributed to genomic and phenomic variation but have been historically difficult to study due to their repetitive nature. Here, we describe a fast and memory-efficient tool to identify novel TIPs from short read sequences. SWIF-TE was able to identify 1,438 insertions at a precision rate of 27% using 0.10 Gb of memory and 0.82 hours of runtime from 15x resequencing data of a non-reference maize inbred. SWIF-TE is a powerful tool for studying TE variation in species with TE-rich genomes.

bioinformatics↗

bioRxiv2024

Structural variants contribute to phenotypic variation in maize

Comprehensively identifying the loci shaping trait variation has been challenging, in part because standard approaches often miss many types of genetic variants. Structural variants (SVs), especially transposable elements (TEs), are likely to affect phenotypic variation but we lack methods that can detect polymorphic structural variants and TEs using short-read sequencing data. Here, we used a whole genome alignment between two maize genotypes to identify polymorphic structural variants and then genotyped a large maize diversity panel for these variants using short-read sequencing data. After characterizing SV variation in the panel, we identified SV polymorphisms that are associated with life history traits and genotype-by-environment (GxE) interactions. While most of the SVs associated with traits contained TEs, only two of the SVs had boundaries that clearly matched TE breakpoints indicative of a TE insertion, while the other polymorphisms were likely caused by deletions. One of the SVs that appeared to be caused by a TE insertion had the most associations with gene expression compared to other trait-associated SVs. All of the SVs associated with traits were in linkage disequilibrium with nearby single nucleotide polymorphisms (SNPs), suggesting that the approach used here did not identify unique associations that would have been missed in a SNP association study. Overall, we have created a technique to genotype SV polymorphisms across a large diversity panel using support from genomic short-read sequencing alignments and connecting this presence/absence SV variation to diverse traits and GxE interactions.

genetics↗

bioRxiv2023

Together Inbreeding and Reproductive Compensation Favor Lethal t-Haplotypes

Male mice who are heterozygous for distorting and non-distorting alleles at the t-haplotype transmit the driving t-haplotype around 90% of the time - a drastic departure from Mendelian expectations. This selfish act comes at a cost. The mechanism underlying transmission distortion in this system causes severe sterility in males homozygous for the drive alleles, ultimately preventing its fixation. Curiously, many driving t-haplotypes also induce embryonic lethality in both sexes when homozygous, however, this is neither universal nor a necessity for this distortion mechanism. Charlesworth provided an adaptive explanation for the evolution of lethal t-haplotypes in a population segregating for distorting and non-distorting t alleles - namely, if mothers compensate by replacing dead embryos with new offspring (or by transferring energy to surviving offspring), a recessive lethal can be favored because it effectively allows mothers the opportunity to trade in infertile males for potentially fertile offspring. However, this model requires near complete reproductive compensation for the invasion of the lethal t-haplotype and produces an equilibrium frequency of lethal drivers well below what is observed in nature. We show that even low levels of systemic inbreeding, which we model as brother-sister mating, allows lethal t-haplotypes to invade with much lower levels of reproductive compensation. Furthermore, inbreeding allows these lethal haplotypes to largely displace the ancestral male-sterile haplotypes. Our results show that together inbreeding and reproductive compensation move expected equilibria closer to observed haplotype frequencies in natural populations and occur under more reasonable parameter combinations.

evolutionary biology↗

bioRxiv2023

Combined analysis of transposable elements and structural variation in maize genomes reveals genome contraction outpaces expansion

BackgroundStructural differences between genomes are a major source of genetic variation that contributes to phenotypic differences. Transposable elements, mobile genetic sequences capable of increasing their copy number and propagating themselves within genomes, can generate structural variation. However, their repetitive nature makes it difficult to characterize fine-scale differences in their presence at specific positions, limiting our understanding of their impact on genome variation. Domesticated maize is a particularly good system for exploring the impact of transposable element proliferation as over 70% of the genome is annotated as transposable elements. High-quality transposable element annotations were recently generated for de-novo genome assemblies of 26 diverse inbred maize lines. ResultsWe generated base-pair resolved pairwise alignments between the B73 maize reference genome and the remaining 25 inbred maize line assemblies. From this data, we classified transposable elements as either shared or polymorphic in a given pairwise comparison. Our analysis uncovered substantial structural variation between lines, representing both putative insertion and deletion events. Putative insertions in SNP depleted regions, which represent recently diverged identity by state blocks, suggest some TE families may still be active. However, our analysis reveals that, genome-wide, deletions of transposable elements account for more structural variation than insertions. These deletions are often large structural variants containing multiple transposable elements. ConclusionsCombined, our results highlight how transposable elements contribute to structural variation and demonstrate that deletion events are a major contributor to genomic differences.

genomics↗

bioRxiv2022

Critical Role of Insertion Preference for Invasion Trajectory of Transposons

Transposable elements (TEs) are mobile DNA sequences that have been highly successful at invading eukaryotic genomes. It is unclear how TE families reach high copy number given the expectation that some novel insertions will be deleterious. It has been hypothesized that TE families may evolve to target and insert into specific DNA sequences to adjust the underlying distribution of fitness effects for new insertions. Preferentially inserting into neutral sites could minimize the cumulative deleterious load of a TE family, allowing the mean TE copy number to increase with less risk for host population extinction. To test this hypothesis, we constructed simulations to explore how the transposition probability and insertion preference of a TE family influence the evolution of mean TE copy number and host population size, allowing for extinction. We find that extinction is most common in our simulations under high transposition probabilities, but, as we reduce transposition rates, the risk of extinction persists while the preference for neutral insertion sites is high. In the absence of mechanisms that regulate TE transposition, a preference for neutral insertion sites is not protective and, in fact, actively accelerates both an increase in TE copy number and the time to population extinction.

evolutionary biology↗

bioRxiv2021

Migration Restores Hybrid Incompatibility Driven By Nuclear-Mitochondrial Sexual Conflict

In the mitochondrial genome, sexual asymmetry in transmission allows the accumulation of male-harming mutations since selection acts only on the effect of the mutation in females. Called the "Mothers Curse", this phenomenon induces a selective pressure for nuclear variants that compensate for this reduction in male fitness. Previous work has demonstrated the existence of these interactions and their potential to act as Dobzhansky-Muller incompatibilities, contributing to reproductive isolation between populations. However, it is not clear how readily they would give rise to and sustain hybrid incompatibilities. Here, we use computer simulations in SLiM 3 to investigate the consequences of sexually antagonistic mitochondrial-nuclear interactions in a subdivided population. We consider distinct migration schemes and vary the chromosomal location, and consequently the transmission pattern, of nuclear restorers. Disrupting these co-evolved interactions results in less-fit males, skewing the sex ratio toward females. Restoration of male fitness depends on both the chromosomal location of nuclear restorer loci and the migration scheme. Our results show that these interactions may act as Dobzhansky-Muller incompatibilities, but their strength is not enough to drive population isolation. Overall, this model shows the varied ways in which populations can respond to migrations disruption of co-evolved mitochondrial-nuclear interactions.

evolutionary biology↗

bioRxiv2019

Mitochondrial-Y chromosome epistasis in Drosophila melanogaster

The coordination between mitochondrial and nuclear genes is crucial to eukaryotic organisms. Predicting the nature of these epistatic interactions can be difficult because of the transmission asymmetry of the genes involved. While autosomes and X-linked genes are transmitted through both sexes, genes on the Y chromosome and in the mitochondrial genome are uniparentally transmitted through males and females respectively. Here, we generate 36 otherwise isogenic Drosophila melanogaster strains differing only in the geographical origin of their mitochondrial genome and Y chromosome to experimentally examine the effects of the uniparentally inherited parts of the genome, as well as their interaction, in males. We assay longevity and gene expression through RNA-sequencing. We detect an important role for both mitochondrial and Y-linked genes, as well as extensive mitochondrial-Y chromosome epistasis, in both traits. In particular, genes involved in male reproduction appear to be especially sensitive. Despite these interactions, we find no evidence that the mitochondrial genome and Y chromosome are co-adapted within a geographic region. Overall, our study demonstrates a key role for the uniparentally inherited parts of the genome for male biology, but also that mito-nuclear interactions are complex and not easily predicted from simple transmission asymmetries.

evolutionary biology↗

bioRxiv2018

Sexual Conflict through Mother’s Curse and Father’s Curse

In contrast with autosomes, lineages of sex chromosomes reside for different amounts of time in males and females, and this transmission asymmetry makes them hotspots for sexual conflict. Similarly, the maternal inheritance of the mitochondrial genome (mtDNA) means that mutations that are beneficial in females can spread in a population even if they are deleterious in males, a form of sexual conflict known as Mothers Curse. While both Mothers Curse and sex chromosome induced sexual conflict have been well studied on their own, the interaction between mitochondrial genes and genes on sex chromosomes is poorly understood. Here, we use analytical models and computer simulations to perform a comprehensive examination of how transmission asymmetries of nuclear, mitochondrial, and sex chromosome-linked genes may both cause and resolve sexual conflicts. For example, the accumulation of male-biased Mothers Curse mtDNA mutations will lead to selection in males for compensatory nuclear modifier loci that alleviate the effect. We show how the Y chromosome, being strictly paternally transmitted provides a particularly safe harbor for such modifiers. This analytical framework also allows us to discover a novel kind of sexual conflict, by which Y chromosome-autosome epistasis may result in the spread of male beneficial but female deleterious mutations in a population. We christen this phenomenon Fathers Curse. Extending this analytical framework to ZW sex chromosome systems, where males are the heterogametic sex, we also show how W-autosome epistasis can lead to a novel kind of nuclear Mothers Curse. Overall, this study provides a comprehensive framework to understand how genetic transmission asymmetries may both cause and resolve sexual conflicts.

evolutionary biology↗