Biology subjects

Fishman, L.

Publications and source records attributed to Fishman, L..

17 recordsLinked to original sources

bioRxiv2026

A centromere but not just a centromere: structure and evolution of a selfish chromosomal supergene in monkeyflowers

Meiotic drivers capitalize on vulnerabilities in eukaryotic meiosis and gametogenesis to gain greater-than-equal transmission to the next generation. In most plants and animals, asymmetric female meiosis is such an arena for selfishness; centromeric variants can bias their chromosomes segregation to the one egg cell with potentially profound effects on individual fitness, population dynamics, and genome structure. However, the mechanisms and consequences of selfish centromere evolution remain obscure, due to both the complexity of centromeric DNA and to a paucity of model systems. Here, we build on representative chromosome-scale assemblies of yellow monkeyflowers (M. guttatus species complex) to compare the structure, gene content, and sequence of three functionally distinct haplotypes at Meiotic Drive Locus on Chromosome 11 (MDL11), whose driving D allele was previously shown to be centromere-containing, costly, and maintained as a balanced polymorphism in wild populations. Relative to both moderately-resistant M. guttatus nondrivers (D-; IM767) and weak (d) M. nasutus, D minimally evolved via two rearrangements (including a hemicentric inversion creating dual arrays of M. guttatus centromeric satellite Cent728 separated by > 200 trapped genes), massive expansions of a novel MDL11-specific subfamily of satellite repeats (Cent728D) that increase D chromosome length by >50%, and the accumulation of >40 extra D-only genes (EDG) from diverse genomic sources in a hemizygous pericentromeric region. Under a strictly centromeric model of selfishness, the recent expansion of Cent728D is a primary candidate for generating centromere drive, either by directly altering the binding of centromeric histone CenH3 or by shifting kinetochore size or position as an epigenetic byproduct of chromosome size. However, elevated divergence in genic presence-absence variants (both in the EDG and elsewhere) and gene sequence across MDL11 strata points to strong candidates for both collusion with the D centromere and for interspecific (D- vs. d) variation in resistance. Overall, our findings support the sequential buildup of this model centromeric driver over time, reveal intriguing parallels with adaptive and gamete-killing supergenes, and provide a strong platform for further dissection of the molecular genetic basis of its dramatic deviations from Mendelian rules.

genetics↗

bioRxiv2025

Novel major loci shape habitat-associated flowering time variation in Yellowstone monkeyflowers

O_LIPlants harbor remarkable genetic diversity in flowering phenology, particularly in their responses to environmental cues such as photoperiod. Understanding the genetic basis of repeated evolution in flowering cues, which are key to reproduction, illuminates adaptation with gene flow and parallel evolution. C_LIO_LIWe characterized variation in minimum critical daylength for flowering (MCD) in yellow monkeyflower (Mimulus guttatus) accessions from a geothermal soil mosaic in Yellowstone National Park, mapped loci underlying the most extreme MCD in focal thermal annuals, and investigated environmental variables shaping phenology in the field. C_LIO_LIYellowstone monkeyflowers range in MCD from 12-15 hours, paralleling range-wide variation in M. guttatus; plants from thermal habitats flower under significantly shorter daylengths. Two QTLs govern the most extreme 12-hour MCD. Both contain candidates from gene families previously implicated in phenological evolution in monkeyflowers and other angiosperms, but the major loci appear novel. The frequency of 12-hour flowering across a microgeographic gradient is predicted by variation in soil temperature and the timing of dry-down. C_LIO_LIAdaptation to Yellowstones geothermal soil mosaic has generated dramatic evolution of flowering cues over short spatial scales. The genetic basis of 12-hour flowering does not indicate re-use of known M. guttatus alleles, but strong candidate genes nonetheless suggest molecular parallelism. C_LI

evolutionary biology↗

bioRxiv2024

An alpine plant shows no decrease in genetic diversity associated with rapid post-glacial range expansion

While range expansion is hypothesized to be a mechanism for species persistence under climate change, many eco-evolutionary models describe demographic and genetic processes during range expansion that may decrease genetic variation and increase genetic load at the leading edge (i.e., expansion load). These predictions are related to dispersal limitation at the leading edge driving colonization dynamics, a scenario common in post-glacial range expansion at the continental scale ([~]20,000 years ago). However, post-glacial range expansion can also occur on contemporary time scales, such as alpine glacier recession following the end of The Little Ice Age ([~]150 years ago) and our understanding of dispersal limitation structuring these instances of rapid range expansion are relatively understudied. Here, we test whether there is evidence supporting the role of dispersal limitation during range expansion following alpine glacier retreat using the native alpine plant Erythranthe (Mimulus) lewisii by examining patterns of neutral genetic diversity (single nucleotide polymorphisms) across the history of glacier recession (i.e., glacier chronosequence) across two glacier forelands in Garibaldi Provincial Park, BC. We find weak support for the prediction of increasing clines in genetic differentiation towards the range edge, and no support for decreasing clines in genetic diversity, suggesting dispersal limitation is not characterizing colonization during range expansion, with the implication that the accumulation of expansion load at the range edge is likely not applicable on these spatiotemporal scales. Together, our results suggest that loss of genetic diversity for range-shifting species in the alpine is likely not a key contributing factor to any decreased fitness over time.

evolutionary biology↗

bioRxiv2024

A comparative analysis across species of maternal mRNA regulation in embryos using QUANTA

AbstractThe post-transcriptional regulation of mRNAs greatly impacts gene expression dynamics, but the underlying regulatory kinetics and sequence rules and how they change between organisms remain elusive. Thousands of pre-loaded maternal transcripts are post-transcriptionally regulated within metazoan embryos, making it an ideal system to investigate mRNA regulation. We present QUANTA, a computational strategy to distinguish transcriptionally silent genes and analyze their regulation. QUANTA uses kinetic models to compare total and polyA+ expression patterns, and dissect quantitative rates of mRNA polyadenylation and degradation. QUANTA analysis of maternally provided mRNAs in zebrafish, frog, mouse and human embryos shows that widespread polyadenylation precedes their degradation. Degradation rates are proportional to the developmental pace of organisms and diverge between orthologs. Rates also scale by adjusting developmental pace of zebrafish with external temperature. Finally, we implement a massively parallel reporter assay that is compatible with QUANTA analysis in zebrafish embryos, and analyze the effects of 3UTR sequences on mRNA kinetics. We pinpoint potential regulatory signals in 3UTRs of each organism. These reveal signals to accelerate maternal degradation in fast-developing organisms, while in slow-developing organisms signals enhance mRNA stability. Our work provides a general strategy to quantify post-transcriptional mRNA kinetics and investigate its sequence-based rules.

systems biology↗

bioRxiv2024

The genetic architecture of floral trait divergence between hummingbird- and self-pollinated monkeyflower (Mimulus) species

O_LIPollination syndromes are a key component of flowering plant diversification, prompting questions about the architecture of single traits and genetic coordination among traits. Here, we investigate the genetics of extreme floral divergence between naturally hybridizing monkeyflowers Mimulus parishii (self-pollinated) and M. cardinalis (hummingbird-pollinated). C_LIO_LIWe mapped quantitative trait loci (QTLs) for 18 pigment, pollinator reward/handling, and dimensional traits in parallel sets of F2 hybrids plus recombinant inbred lines and generated nearly isogenic lines (NILs) for two dimensional traits, pistil length and corolla size. C_LIO_LIOur multi-population approach revealed a highly polygenic basis (n = 190 QTLs total) for pollination syndrome divergence, capturing minor QTLs even for pigment traits with leading major loci. There was significant QTL overlap within pigment and dimensional categories. Nectar volume QTLs clustered with those for floral dimensions, suggesting a partially shared module. The NILs refined two pistil length QTLs, only one of which has tightly correlated effects on other dimensional traits. C_LIO_LIAn overall polygenic architecture of floral divergence is partially coordinated by genetic modules formed by linkage (pigments) and likely pleiotropy (dimensions plus nectar). This work illuminates pollinator syndrome evolution in a model radiation and generates a robust framework for molecular and ecological genomics. C_LI

evolutionary biology↗

bioRxiv2024

Undoing the 'nasty: dissecting touch-sensitive stigma movement (thigmonasty) and its loss in self-pollinating monkeyflowers

Rapid touch-sensitive stigma closure is a novel plant reproductive trait found in hundreds of Lamiales species. The origins, mechanisms, and functions of stigma closure remain poorly understood, but its repeated loss in self-fertilizing taxa and direct tests implicate adaptive roles in animal-mediated cross-pollination. Here, we document several additional losses of stigma closure in monkeyflowers (Mimulus), then use quantitative trait locus (QTL) mapping and gene expression analyses to provide a first glimpse into the genetic and molecular basis of stigma mechanosensing and movement. Variation in stigma closure in hybrids between selfer/non-closer Mimulus nasutus and outcrosser/fast-closer M. guttatus has a moderately complex genetic basis, with four QTLs together explaining [~]70% of parental divergence.Loss of stigma closure in M. nasutus appears genetically independent from other aspects of the floral selfing syndrome and from a parallel loss in M. parishii. Analyses of stylar gene expression in closer M. guttatus, M. nasutus, and a rare M. guttatus non-closer genotype identify functional candidates involved in mechanosensing, turgor regulation, and cell wall remodeling. Together, these analyses reveal a polygenic genetic architecture underlying gain and loss of a novel plant movement, illuminate selfer-outcrosser reproductive divergence, and initiate mechanistic investigations of an unusually visible manifestation of plant intelligence.

plant biology↗

bioRxiv2023

Genomic mechanisms and consequences of diverse postzygotic barriers between monkeyflower species

The evolution of genomic incompatibilities causing postzygotic barriers to hybridization is a key step in species divergence. Incompatibilities take two general forms - structural divergence between chromosomes leading to severe hybrid sterility in F1 hybrids and epistatic interactions between genes causing reduced fitness of hybrid gametes or zygotes (Dobzhansky-Muller incompatibilities). Despite substantial recent progress in understanding the molecular mechanisms and evolutionary origins of both types of incompatibility, how each behaves across multiple generations of hybridization remains relatively unexplored. Here, we use genetic mapping in F2 and RIL hybrid populations between the phenotypically divergent but naturally hybridizing monkeyflowers Mimulus cardinalis and M. parishii to characterize the genetic basis of hybrid incompatibility and examine its changing effects over multiple generations of experimental hybridization. In F2s, we found severe hybrid pollen inviability (< 50% reduction vs. parental genotypes) and pseudolinkage caused by a reciprocal translocation between Chromosomes 6 and 7 in the parental species. RILs retained excess heterozygosity around the translocation breakpoints, which caused substantial pollen inviability when interstitial crossovers had not created compatible heterokaryotypic configurations. Strong transmission ratio distortion and inter-chromosomal linkage disequilibrium in both F2s and RILs identified a novel two-locus genic incompatibility causing sex-independent gametophytic (haploid) lethality. The latter interaction eliminated three of the expected nine F2 genotypic classes via F1 gamete loss without detectable effects on the pollen number or viability of F2 double heterozygotes. Along with the mapping of numerous milder incompatibilities, these key findings illuminate the complex genetics of plant hybrid breakdown and are an important step toward understanding the genomic consequences of natural hybridization in this model system.

genetics↗

bioRxiv2023

Single-cell temporal dynamics reveals the relative contributions of transcription and degradation to cell-type specific gene expression in zebrafish embryos

AbstractDuring embryonic development, pluripotent cells assume specialized identities by adopting particular gene expression profiles. However, systematically dissecting the underlying regulation of mRNA transcription and degradation remains a challenge, especially within whole embryos with diverse cellular identities. Here, we collect temporal cellular transcriptomes of zebrafish embryos, and decompose them into their newly-transcribed (zygotic) and pre-existing (maternal) mRNA components by combining single-cell RNA-Seq and metabolic labeling. We introduce kinetic models capable of quantifying regulatory rates of mRNA transcription and degradation within individual cell types during their specification. These reveal different regulatory rates between thousands of genes, and sometimes between cell types, that shape spatio-temporal expression patterns. Transcription drives most cell-type restricted gene expression. However, selective retention of maternal transcripts helps to define the gene expression profiles of germ cells and enveloping layer cells, two of the earliest specified cell-types. Coordination between transcription and degradation restricts expression of maternal-zygotic genes to specific cell types or times, and allows the emergence of spatio-temporal patterns when overall mRNA levels are held relatively constant. Sequence-based analysis links differences in degradation to specific sequence motifs. Our study reveals mRNA transcription and degradation events that control embryonic gene expression, and provides a quantitative approach to study mRNA regulation during a dynamic spatio-temporal response.

genomics↗

bioRxiv2022

A local sequence signature defines a subset of heterochromatin-associated CpGs with minimal loss of methylation in healthy tissues but extensive loss in cancer

Global loss of DNA methylation in mammalian genomes occurs during aging and cancer, primarily in heterochromatin-associated Partially Methylated Domains (PMDs). It has previously been shown that local sequence context (100bp) has a strong influence on the rate of demethylation of individual CpG dinucleotides within PMDs. Here, we train a deep learning model to capture this sequence dependence, finding that methylation loss in healthy tissues and cancer can be predicted with high accuracy based on the 150bp surrounding a CpG. We use a published whole-genome map of the re-methylation rate of newly synthesized DNA during mitosis to show that CpGs with a "slow-loss" sequence context are efficiently re-methylated, while CpGs with a "fast-loss" sequence context are inefficiently re-methylated. Intriguingly, we find that the 10% most slow-loss CpGs lose almost no DNA methylation in healthy cell types, but lose significant DNA methylation in many cancer types. This finding suggests that loss of DNA methylation at slow-loss CpGs could underlie some cancer-specific transcriptional deregulation that has been linked to DNA hypomethylation, including the derepression of cancer antigens and transposable elements.

genomics↗

bioRxiv2021

Population genomic consequences of novel life history and mating system adaptation to a geothermal soil mosaic in yellow monkeyflowers (Mimulus guttatus)

Local selection can promote phenotypic divergence despite gene flow across habitat mosaics, but adaptation itself may generate substantial barriers to genetic exchange. In plants, life-history, phenology, and mating system divergence have been particularly proposed to promote genetic differentiation in sympatry. In this study, we investigate phenotypic and genetic variation in Mimulus guttatus (yellow monkeyflowers) across a geothermal soil mosaic in Yellowstone National Park (YNP). Plants from thermal annual and nonthermal perennial habitats were heritably differentiated for life history and mating system traits, consistent with local adaptation to the ephemeral thermal-soil growing season. However, genome-wide genetic variation primarily clustered plants by geographic region, with little variation sorting by habitat. The one exception was an extreme thermal population also isolated by a 200m geographical gap. Individual inbreeding coefficients (FIS) were higher (and predicted by trait variation) in annual plants and annual pairs showed greater isolation by distance at local (<1km) scales. Finally, YNP adaptation does not re-use a widespread inversion polymorphism diagnostic of annual vs. perennial M. guttatus range-wide, suggesting a novel genetic mechanism. Overall, this work suggests that life history and mating system adaptation strong enough to shape individual mating patterns does not necessarily generate incipient speciation without geographical barriers.

evolutionary biology↗

bioRxiv2020

Divergence in bidirectional plant-soil feedbacks between montane annual and coastal perennial ecotypes of yellow monkeyflower (Mimulus guttatus)

O_LIUnderstanding the physiological and genetic mechanisms underlying plant variation in interactions with root-associated biota (RAB) requires a micro-evolutionary approach. We use locally adapted montane annual and coastal perennial ecotypes of Mimulus guttatus (yellow monkeyflower) to examine population-scale differences in plant-RAB-soil feedbacks. C_LIO_LIWe characterized fungal communities for the two ecotypes in-situ and used a full-factorial greenhouse experiment to investigate the effects of plant ecotype, RAB source, and soil origin on plant performance and endophytic root fungal communities. C_LIO_LIThe two ecotypes harbored different fungal communities and responsiveness to soil biota was highly context-dependent. Soil origin, RAB source, and plant ecotype all affected the intensity of biotic feedbacks on plant performance. Feedbacks were primarily negative, and we saw little evidence of local adaptation to either soils or RAB. Both RAB source and soil origin significantly shaped fungal communities in roots of experimental plants. Further, the perennial ecotype was more colonized by arbuscular mycorrhizal fungi (AMF) than the montane ecotype, and preferentially recruited home AMF taxa. C_LIO_LIOur results suggest life history divergence and distinct edaphic habitats shape plant responsiveness to RAB and influence specific associations with potentially mutualistic root endophytic fungi. Our results advance the mechanistic study of intraspecific variation in plant-soil-RAB interactions. C_LI

ecology↗

bioRxiv2020

Selfish chromosomal drive shapes recent centromeric histone evolution in monkeyflowers

Under the selfish centromere model, costs associated with female meiotic drive by centromeres select on interacting kinetochore proteins to restore Mendelian inheritance. We directly test this model in yellow monkeyflowers (Mimulus guttatus), which are polymorphic for a costly driving centromere (D). We show that the D haplotype is structurally and genetically distinct and swept to a high stable frequency within the past 1500 years. Quantitative genetic analyses reveal that variation in the strength of drive primarily depends on the identity of the non-D centromere, but also identified an unlinked modifier coincident with kinetochore protein Centromere-specific Histone 3 A (CenH3A). CenH3A has also experienced a recent (<1000 years) selective sweep in our focal population, consistent with ongoing interactions with D shaping its evolution. Together, our results demonstrate an active co-evolutionary arms race between the DNA and protein components of the meiotic machinery, with important consequences for individual fitness and molecular divergence.

evolutionary biology↗

bioRxiv2020

Ancient and recent introgression shape the evolutionary history of pollinator adaptation and speciation in a model monkeyflower radiation (Mimulus section Erythranthe)

Inferences about past processes of adaptation and speciation require a gene-scale and genome-wide understanding of the evolutionary history of diverging taxa. In this study, we use genome-wide capture of nuclear gene sequences, plus skimming of organellar sequences, to investigate the phylogenomics of monkeyflowers in Mimulus section Erythranthe (27 accessions from seven species). Taxa within Erythranthe, particularly the parapatric and putatively sister species M. lewisii (bee-pollinated) and M. cardinalis (hummingbird-pollinated), have been a model system for investigating the ecological genetics of speciation and adaptation for over five decades. Across >8000 nuclear loci, multiple methods resolve a predominant species tree in which M. cardinalis groups with other hummingbird-pollinated taxa (37% of gene trees), rather than being sister to M. lewisii (32% of gene trees). We independently corroborate a single evolution of hummingbird pollination syndrome in Erythranthe by demonstrating functional redundancy in genetic complementation tests of floral traits in hybrids; together, these analyses overturn a textbook case of pollination-syndrome convergence. Strong asymmetries in allele-sharing (Pattersons D-statistic and related tests) indicate that gene-tree discordance reflects ancient and recent introgression rather than incomplete lineage sorting. Consistent with abundant introgression blurring the history of divergence, low-recombination and adaptation-associated regions support the new species tree, while high-recombination regions generate phylogenetic evidence for sister status for M. lewisii and M. cardinalis. Population-level sampling of core taxa also revealed two instances of chloroplast capture, with Sierran M. lewisii and Southern Californian M. parishii each carrying organelle genomes nested within respective sympatric M. cardinalis clades. A recent organellar transfer from M. cardinalis, an outcrosser where selfish cytonuclear dynamics are more likely, may account for the unexpected cytoplasmic male sterility effects of selfer M. parishii organelles in hybrids with M. lewisii. Overall, our phylogenomic results reveal extensive reticulation throughout the evolutionary history of a classic monkeyflower radiation, suggesting that natural selection (re-)assembles and maintains species-diagnostic traits and barriers in the face of gene flow. Our findings further underline the challenges, even in reproductively isolated species, in distinguishing re-use of adaptive alleles from true convergence and emphasize the value of a phylogenomic framework for reconstructing the evolutionary genetics of adaptation and speciation. Author SummaryAdaptive radiations, which involve both divergent evolution of new traits and recurrent trait evolution, provide insight into the processes that generate and maintain organismal diversity. However, rapid radiations also generate particular challenges for inferring the evolutionary history and mechanistic basis of adaptation and speciation, as multiple processes can cause different parts of the genome to have distinct phylogenetic trees. Thus, inferences about the mode and timing of divergence and the causes of parallel trait evolution require a fine-grained understanding of the flow of genomic variation through time. In this study, we used genome-wide sampling of thousands of genes to re-construct the evolutionary histories of a model plant radiation, the monkeyflowers of Mimulus section Erythranthe. Work over the past half-century has established the parapatric and putatively sister species M. lewisii (bee-pollinated) and M. cardinalis (hummingbird-pollinated, as are three other species in the section) as textbook examples of both rapid speciation via shifts in pollination syndrome and convergent evolution of floral syndromes. Our phylogenomic analyses re-write both of these stories, placing M. cardinalis in a clade with other hummingbird-pollinated taxa and demonstrating that abundant introgression between ancestral lineages as well as in areas of current sympatry contributes to the real (but misleading) affinities between M. cardinalis and M. lewisii. This work illustrates the pervasive influence of gene flow and introgression during adaptive radiation and speciation, and underlines the necessity of a gene-scale and genome-wide phylogenomics framework for understanding trait divergence, even among well-established species.

evolutionary biology↗

bioRxiv2020

Quantitative trait locus mapping reveals an independent genetic basis for joint divergence in leaf function, life-history, and floral traits between scarlet monkeyflower (Mimulus cardinalis) populations

PREMISEAcross taxa, vegetative and floral traits that vary along a fast-slow life-history axis are often correlated with leaf functional traits arrayed along the leaf economics spectrum, suggesting a constrained set of adaptive trait combinations. Such broad-scale convergence may arise from genetic constraints imposed by pleiotropy (or tight linkage) within species, or from natural selection alone. Understanding the genetic basis of trait syndromes and their components is key to distinguishing these alternatives and predicting evolution in novel environments. METHODSWe used a line-cross approach and quantitative trait locus (QTL) mapping to characterize the genetic basis of twenty leaf functional/physiological, life history, and floral traits in hybrids between annualized and perennial populations of scarlet monkeyflower (Mimulus cardinalis). RESULTSWe mapped both single and multi-trait QTLs for life history, leaf function and reproductive traits, but found no evidence of genetic co-ordination across categories. A major QTL for three leaf functional traits (thickness, photosynthetic rate, and stomatal resistance) suggests that a simple shift in leaf anatomy may be key to adaptation to seasonally dry habitats. CONCLUSIONSOur results suggest that the co-ordination of resource-acquisitive leaf physiological traits with a fast life history and more selfing mating system results from environmental selection rather than functional or genetic constraint. Independent assortment of distinct trait modules, as well as a simple genetic basis to leaf physiological traits associated with drought escape, may facilitate adaptation to changing climates.

plant biology↗

bioRxiv2020

Predicting evolutionary change at the DNA level in a natural Mimulus population

Evolution by natural selection occurs when the frequencies of genetic variants change because individuals differ in Darwinian fitness components such as survival or reproductive success. Differential fitness has been demonstrated in field studies of many organisms, but our ability to quantitatively predict allele frequency changes from fitness measurements remains unclear. Here, we characterize natural selection on millions of Single Nucleotide Polymorphisms (SNPs) across the genome of the annual plant Mimulus guttatus. We use fitness estimates to calibrate population genetic models that effectively predict observed allele frequency changes into the next generation. Hundreds of SNPs experienced "male selection" in 2013 with one allele at each SNP elevated in frequency among successful male gametes relative to the entire population of adults. In the following generation, allele frequencies at these SNPs consistently shifted in the predicted direction. A second year of study revealed that SNPs had effects on both viability and reproductive success with pervasive trade-offs between fitness components. SNPs favored by male selection were, on average, detrimental to survival. These trade-offs (antagonistic pleiotropy and temporal fluctuations in fitness) may be essential to the long-term maintenance of alleles undergoing substantial changes from generation to generation. Despite the challenges of measuring selection in the wild, the strong correlation between predicted and observed allele frequency changes suggests that population genetic models have a much greater role to play in forward-time prediction of evolutionary change. Author summaryFor the last 100 years, population geneticists have been deriving equations for {Delta}p, the change in allele frequency owing to mutation, selection, migration, and genetic drift. Seldom are these equations used directly, to match a prediction for {Delta}p to an observation of {Delta}p. Here, we apply genomic sequencing technologies to samples from natural populations, obtaining millions of observations of {Delta}p. We estimate natural selection on SNPs in a natural population of yellow monkeyflowers and find extensive evidence for selection through differential male success. We use the SNP-specific fitness estimates to calibrate a population genetic model that predicts observed {Delta}p into the next generation. We find that when male selection favored one nucleotide at a SNP, that nucleotide increased in frequency in the next generation. Since neither observed nor predicted {Delta}p are generally large in magnitude, we developed a novel method called "haplotype matching" to improve prediction accuracy. The method leverages intensive whole genome sequencing of a reference panel (187 individuals) to infer sequence-specific selection in thousands of field individuals sequenced at much lower coverage. This method proved essential to accurately predicting {Delta}p in this experiment and further development may facilitate population genetic prediction more generally.

evolutionary biology↗

bioRxiv2018

Extreme copy number variation at a tRNA ligase affecting phenology and fitness in yellow monkeyflowers

Copy number variation (CNV) is a major part of the genetic diversity segregating within populations, but remains poorly understood relative to single nucleotide variation. Here, we report on a tRNA ligase gene (Migut.N02091; RLG1a) exhibiting unprecedented, and fitness-relevant, CNV within an annual population of the yellow monkeyflower Mimulus guttatus. RLG1a variation was associated with multiple traits in pooled population sequencing (PoolSeq) scans of phenotypic and phenological cohorts. Resequencing of inbred lines revealed intermediate frequency three-copy variants of RLG1a (trip+; 5/35 = 14%), and trip+ lines exhibited elevated RLG1a expression under multiple conditions. trip+ carriers, in addition to being over-represented in late-flowering and large-flowered PoolSeq populations, flowered later under stressful conditions in a greenhouse experiment (P < 0.05). In wild population samples, we discovered an additional rare RLG1a variant (high+) that carries 250-300 copies of RLG1a totaling [~]5.7Mb (20-40% of a chromosome). In the progeny of a high+ carrier, Mendelian segregation of diagnostic alleles and qPCR-based copy counts indicate that high+ is a single tandem array unlinked from the single copy RLG1a locus. In the wild, high+ carriers had highest fitness in two particularly dry and/or hot years (2015 and 2017; both p < 0.01), while single copy individuals were twice as fecund as either CNV type in a lush year (2016: p < 0.005). Our results demonstrate fluctuating selection on CNVs affecting phenological traits in a wild population, suggest that plant tRNA ligases mediate stress-responsive life-history traits, and introduce a novel system for investigating the molecular mechanisms of gene amplification.

evolutionary biology↗

bioRxiv2018

A synthesis of mapping experiments reveals extensive genomic structural diversity in the Mimulus guttatus species complex

Understanding genomic structural variation such as inversions and translocations is a key challenge in evolutionary genetics. In this paper, we tackle this challenge by developing a novel statistical approach to comparative genetic mapping. The procedure couples a Hidden Markov Model with a Genetic Algorithm to detect large-scale structural variation using low-level sequencing data from multiple genetic mapping populations. We demonstrate the method using five distinct crosses within the flowering plant genus Mimulus. The synthesis of data from these experiments is first used to correct numerous errors (misplaced sequences) in the M. guttatus reference genome. Second, we confirm and/or detect eight large inversions polymorphic within the M. guttatus species complex. Finally, we show how this method can be applied in genomic scans to improve the accuracy and resolution of Quantitative Trait Locus (QTL) mapping.\n\nAUTHOR SUMMARYGenome sequences have proved to be a critical experimental resource for genetic research in many species. However, in some species there is considerable variation in genomic organization, making a single reference genome sequence inadequate. This variation can cause issues in interpreting genomic signals, such as those coming from trait mapping. We introduce a new statistical method and computational tools that use linkage information to reorganize a single reference genome to 1) repair genome assembly errors, and 2) identify variation between individuals or populations of the same species. Using this method we can create a new genome order that improves upon the reference genome. We apply this method to five crosses among plants in the Mimulus guttatus species complex. In this system we detect eight large chromosomal inversions and improve the resolution of a trait mapping study. This work highlights the utility of our method, and indicates how others studying diverse species might use them to improve their own research.

genetics↗