Biology subjects

Lane, N.

Publications and source records attributed to Lane, N..

14 recordsLinked to original sources

bioRxiv2026

Mitonuclear interactions shape male cuticular hydrocarbon profiles with consequences on mating success

Sexual signals are thought to reflect metabolic capacity, allowing females to assess male genetic quality. In insects, cuticular hydrocarbons (CHCs) are central to mate recognition and sexual signalling, and their biosynthesis is directly tied to mitochondrial metabolism. Because mitochondrial performance requires coordination between the mitochondrial and nuclear genomes, non-compatible genomes may disrupt CHC production and reduce male attractiveness. We tested this prediction using a global Drosophila melanogaster mitonuclear panel comprising 80 cybrid genotypes. Multivariate analyses of male CHC profiles revealed strong nuclear effects, smaller but significant mitochondrial effects, and substantial non-additive mitonuclear interactions that accounted for ~10% of the variance after controlling for body mass. These interactions reorganised CHC blends in genotype-specific ways, with certain hydrocarbons contributing disproportionately to differentiation. In behavioural assays, females preferentially mated with males whose mitonuclear genomes were coadapted. Conversely, coadapted males had higher copulation success than males presenting disrupted combinations to the female. Our results demonstrate that mitonuclear compatibility influences the production of sexual signals and shapes reproductive outcomes, linking genomic interactions to mate choice.

evolutionary biology↗

bioRxiv2025

First growth, then information: the path to genetic heredity in protocells

Most theoretical work on the origin of heredity has focused on how genetic information can be maintained without mutational degradation in the absence of error-proofing systems. A simple and parsimonious solution assumes the first gene sequences evolved inside dividing protocells, which enables selection for functional sets. But these models of information maintenance do not consider how protocells acquired their genetic information in the first place. Clues to this transition are suggested by patterns in the genetic code, which indicate a strong link to autotrophic metabolism, with early translation based on direct physical interactions between amino acids and short RNA polymers, grounded in their hydrophobicity. Here, we develop a mathematical model to investigate how random RNA polymers inside autotrophically growing protocells could evolve better coding sequences for discrete functions. The model tracks a population of protocells that evolve towards two essential functions: CO2 fixation (which drives monomer synthesis and cell growth) and copying (which amplifies replication and translation of sequences inside protocells). The model shows that distinct coding sequences can emerge from random RNA sequences driving increased protocell division. The analysis reveals an important restriction: growth-supporting functions such as CO2 fixation must be more easily attained than informational processes such as RNA copying and translation. This uncovers a fundamental constraint on the emergence of genetic heredity: growth precedes information at the origin of life.

evolutionary biology↗

bioRxiv2025

N-acetyltransferase 10 promotes mRNA stability of immune response factors to modulate Zika virus infection

Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that poses serious risks to human health. In previous work, we used RNA immunoprecipitation and mass spectrometry to show that more than 30 distinct RNA modifications, or chemical moieties, were present on the RNA genome of ZIKV. Among these, N4-acetylcytosine (ac4C) was one of the most abundant modifications. In this study, we investigated the role of N-acetyltransferase 10 (NAT10), the writer enzyme that acetylates cytidine, in ZIKV gene expression. Using NAT10 knockout cell lines, RNA interference (RNAi), and overexpression rescue strategies, we found that loss of NAT10 led to increased levels of ZIKV protein and RNA. However, the production of infectious virus particles was not significantly affected. Interestingly, in NAT10-deficient cells compared to wild-type (WT) cells, ZIKV protein and RNA were detectable earlier during infection, suggesting that the loss of NAT10 facilitated increased viral replication. Despite this increase, ZIKV RNA was more rapidly degraded, although the accumulation of small flaviviral RNAs was not significantly altered by the absence of NAT10. Further analysis of key components of the innate immune response revealed that, in the absence of NAT10 and during early infection, STAT1, IFIT1, and MX1 mRNA transcripts were rapidly degraded, leading to reduced expression of the respective innate immune proteins. Taken together, our findings demonstrate that NAT10, the ac4C writer enzyme, modulates the stability of specific innate immune mRNAs and thereby plays a regulatory role in ZIKV infection dynamics. IMPORTANCERNA modifications are chemical groups that are deposited post-transcriptionally on RNA. In recent years, RNA modifications in viral RNAs have been shown to have profound effects on viral gene expression and hence viral function. Indeed, numerous studies have investigated the role of N6-methyladenosine and 5-methylcytosine RNA modifications and the respective enzymes that deposit (writer), remove (eraser) and facilitate (reader) function on viral infection. In this study we show how N4-acetyltransferase 10 (NAT10), a writer enzyme that acetylates cytidine to form N4-acetylcytidine (ac4C), affects Zika virus gene expression. Specifically, we found that NAT10 regulates viral infection kinetics by affecting the stability of select mRNAs involved in the innate immune response pathway. Our findings highlight another mode by which the innate immune response is robustly regulated in response to ZIKV infection.

microbiology↗

bioRxiv2025

Eukaryotic recombinases duplicated after divergence from known asgardarchaeal RadA: implications for the evolution of sex during eukaryogenesis

The origin of meiotic sex was a key milestone in the evolution of the eukaryotic cell. The DNA recombinases Rad51 and DMC1 have been used previously to trace the timing and origins of the meiotic machinery, and warrant revisiting in the face of the recent increased diversity of reported asgardarchaeal taxa. Here we perform comparative genomics and phylogenetic analyses of RadA protein sequences from a broad sampling of eukaryotic and archaeal taxa. We show that even with increased and new sampling, the eukaryotic Rad51 and DMC1 proteins still resolve separately from any archaeal RadA sequences. Taking into account recent evolutionary cell biological discoveries, our data are most consistent with a scenario whereby the asgardarchaeal host cell was evolving cytoskeletal and membrane-protein machinery that was later incorporated into eukaryotic endomembrane systems following the acquisition of mitochondria and the evolution of sex.

evolutionary biology↗

bioRxiv2023

Prebiotic membrane structures mimic the morphology of purported early traces of life on Earth

Elucidating the most probable compositions of the first cell membranes prior to the origin of life, within a laboratory setting, requires experiments with organic molecules and chemical conditions representative of those present on the early Earth. As such, the membrane forming molecules used in these experiments are described as prebiotically plausible, i.e., they could have formed through abiotic reactions and be available for membrane formation prior to the emergence of biology. Similarly, the chemical properties of solutions in which these membranes are formed (e.g., pH, temperature, ionic strength) must represent the early Earth environmental conditions under investigation. Here, using a combined confocal and transmission electron microscopy approach, we show that prebiotically plausible organic molecules, in solutions representative of Hadean submarine alkaline hydrothermal vents, form aggregated structures with substantial morphological diversity. The structures hold the potential for use as traces of prebiotic processes in the ancient rock record. In addition, many of the structures are morphologically similar to those which are presented as early microfossils, thus highlighting the limitations of morphological interpretation in these types of studies. Detailed analyses of abiotic organic structures are essential for our understanding of the earliest living organisms on Earth, as well as for our interpretation of any potential biosignatures recovered in the future from extra-terrestrial bodies.

paleontology↗

bioRxiv2023

Assessing the role of mitonuclear interactions on mitochondrial function and organismal fitness in natural Drosophila populations

Mitochondrial metabolism is regulated by a series of enzyme complexes, whose function depends on effective interactions between proteins and RNA encoded by the mitochondrial and nuclear genomes. These epistatic interactions are in turn highly sensitive to the environment. Many studies have found that mitochondrial haplotype frequencies of various taxa associate with latitude or altitude, leading to the hypothesis that mitochondrial genomes may respond to thermal selection and contribute to local adaptation. We used a Drosophila melanogaster panel comprising native (coadapted) populations from the extremes of the Australian east-coast cline, and generated mitonuclear cybrid populations. Our results indicate a strong phenotypic impact of mitonuclear interactions in cybrid lines, involving an apparent trade-off between aerobic capacity and key fitness aspects such as reproduction, growth, and survival. Overall, our study shows that naturally-occurring mitonuclear disruptions can have a meaningful impact on phenotypes, potentially influencing future ecological adaptation and population persistence.

evolutionary biology↗

bioRxiv2022

Repeat sequences limit the effectiveness of LGT and favoured the evolution of meiotic sex in early eukaryotes

The transition from prokaryotic lateral gene transfer to eukaryotic meiotic sex is poorly understood. Phylogenetic evidence suggests that it was tightly linked to eukaryogenesis, which involved an unprecedented rise in both genome size and the density of genetic repeats. Expansion of genome size raised the severity of Mullers ratchet, whilst limiting the effectiveness of lateral gene transfer (LGT) at purging deleterious mutations. In principle, an increase in recombination length combined with higher rates of LGT could solve this problem. Here we show using a computational model that this solution fails in the presence of genetic repeats prevalent in early eukaryotes. The model demonstrates that dispersed repeat sequences allow ectopic recombination, which leads to the loss of genetic information and curtails the capacity of LGT to prevent mutation accumulation. Increasing recombination length in the presence of repeat sequences exacerbates the problem. Mutational decay can only be resisted with homology along extended sequences of DNA. We conclude that the transition to homologous pairing along linear chromosomes was a key innovation in meiotic sex, which was instrumental in the expansion of eukaryotic genomes and morphological complexity. Relevance StatementThe origin of meiotic sex is a long-standing evolutionary enigma. This novel mechanism of reproduction replaced lateral gene transfer (LGT), the uptake and recombination of pieces of environmental DNA seen in bacteria and archaea. We link its origin to the expanded genome size and proliferation of genetic repeats found in early eukaryotes. Both factors led to high levels of mutation accumulation and gene loss under LGT which could not be retarded through increases in the rate of LGT or the length of DNA recombined. Meiotic sex with homologous pairing of long chromosome sized pieces of DNA promoted purifying selection and supressed ectopic recombination. It permitted the evolution of the expanded genome needed for the evolution of complex eukaryotic life.

evolutionary biology↗

bioRxiv2022

Mitonuclear interactions produce extreme differences in response to redox stress

Incompatibilities between mitochondrial and nuclear genes can perturb respiration, biosynthesis, signalling and gene expression. Here we investigate whether mild mitonuclear incompatibilities alter response to redox stress induced by N-acetyl cysteine (NAC). We studied three Drosophila melanogaster lines with mitochondrial genomes either coevolved (WT) or mildly mismatched (BAR, COX) to an isogenic nuclear background. Responses to NAC varied substantially with mitonuclear genotype, sex, tissue and dose. NAC caused infertility and high mortality in some groups but not others. Using tissue-specific fluorespirometry, we show that NAC did not alter H2O2 flux but suppressed complex I-linked respiration in female flies, maintaining a reduced glutathione pool. High mortality in BAR females was associated with severe suppression of complex I-linked respiration, rising H2O2 flux in ovaries and oxidation of the glutathione pool. Our results suggest that redox stress is attenuated by suppression of complex-I linked respiration, to the point of death in some mitonuclear lines.

biochemistry↗

bioRxiv2022

The limits of metabolic heredity in protocells

The universal core of metabolism could have emerged from thermodynamically favoured prebiotic pathways at the origin of life. Starting with H2 and CO2, the synthesis of amino acids and mixed fatty acids, which self-assemble into protocells, is favoured under warm anoxic conditions. Here we address whether it is possible for protocells to evolve greater metabolic complexity, through positive feedbacks involving nucleotide catalysis. Using mathematical simulations to model metabolic heredity in protocells, based on branch points in proto-metabolic flux, we show that nucleotide catalysis can indeed promote protocell growth. This outcome only occurs when nucleotides directly catalyse CO2 fixation. Strong nucleotide catalysis of other pathways (e.g. fatty acids, amino acids) generally unbalances metabolism and slows down protocell growth, and when there is competition between catalytic functions cell growth collapses. Autocatalysis of nucleotide synthesis can promote growth but only if nucleotides also catalyse CO2 fixation; autocatalysis alone leads to the accumulation of nucleotides at the expense of CO2 fixation and protocell growth rate. Our findings offer a new framework for the emergence of greater metabolic complexity, in which nucleotides catalyse broad-spectrum processes such as CO2 fixation, hydrogenation and phosphorylation important to the emergence of genetic heredity at the origin of life.

evolutionary biology↗

bioRxiv2021

A prebiotic basis for ATP as the universal energy currency

ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires six phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP-equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleotide triphosphates, remains a mystery. Here we show that the deep conservation of ATP reflects its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate, which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that acetyl phosphate can phosphorylate ADP to ATP at nearly 20 % yield in water in the presence of Fe3+ ions. We then show that Fe3+ and acetyl phosphate are surprisingly favoured: a panel of other prebiotically relevant ions and minerals did not catalyze ADP phosphorylation; nor did a number of other potentially prebiotic phosphorylating agents. Only carbamoyl phosphate showed some modest phosphorylating activity. Critically, we show that acetyl phosphate does not phosphorylate other nucleotide diphosphates or free pyrophosphate in water. The phosphorylation of ADP monomers seems to be favoured by the interaction between the N6 amino group on the adenine ring with Fe3+ coupled to acetyl phosphate. Our findings suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.

biochemistry↗

bioRxiv2020

Mother's curse is pervasive across a large mito-nuclear Drosophila panel

The maternal inheritance of mitochondrial genomes entails a sex-specific selective sieve, whereby mutations in mitochondrial DNA can only respond to selection acting directly on females. In theory, this enables male-harming mutations to accumulate in mitochondrial genomes if they are neutral, beneficial, or only slightly deleterious to females. Ultimately, this bias could drive the evolution of male-specific mitochondrial mutation loads, an idea known as mothers curse. Earlier work on this hypothesis has mainly used small Drosophila panels, in which naturally-sourced mitochondrial genomes were coupled to an isogenic nuclear background. However, the lack of nuclear genetic variation has precluded robust generalization. Here we test the predictions of mothers curse using a large Drosophila mito-nuclear genetic panel, comprising 9 isogenic nuclear genomes coupled to 9 mitochondrial haplotypes, giving a total of 81 different mito-nuclear genotypes. This enables systematic testing of both mito-nuclear interactions and mitochondrial genetic variance. Following a predictive framework, we performed a screen for wing centroid size, as this trait is highly sexually dimorphic and depends on metabolic function. We confirmed that the trait is sexually dimorphic, and show high levels of mito-nuclear epistasis. Importantly, we report that mitochondrial genetic variance has a greater impact on male versus female Drosophila, in 8 out of the 9 nuclear genetic backgrounds. These results demonstrate that the maternal inheritance of mitochondrial DNA does indeed modulate male life-history traits in a more generalisable way than previously envisaged.

evolutionary biology↗

bioRxiv2020

The need for high-quality oocyte mitochondria at extreme ploidy dictates germline development

Selection against deleterious mitochondrial mutations is facilitated by germline processes, lowering the risk of genetic diseases. How selection works is disputed: experimental data are conflicting and previous modelling work has not clarified the issues. Here we develop computational and evolutionary models that compare the outcome of selection at the level of individuals, cells and mitochondria. Using realistic de novo mutation rates and germline development parameters, the evolutionary model predicts the observed prevalence of mitochondrial mutations and diseases in human populations. We show the importance of organelle-level selection, seen in the selective pooling of mitochondria into the Balbiani body, in achieving high-quality mitochondria at extreme ploidy in mature oocytes. Alternative mechanisms debated in the literature, bottlenecks and follicular atresia, are unlikely to account for the clinical data, because neither process effectively eliminates mitochondrial mutations under realistic conditions. Our findings explain the major features of female germline architecture, notably the longstanding paradox of over-proliferation of primordial germ cells followed by massive loss. The near-universality of these processes across animal taxa makes sense in light of the need to maintain mitochondrial quality at extreme ploidy in mature oocytes, in the absence of sex and recombination.

evolutionary biology↗

bioRxiv2020

Genome expansion in early eukaryotes drove the transition from lateral gene transfer to meiotic sex

Prokaryotes generally reproduce clonally but can also acquire new genetic material via lateral gene transfer (LGT). Like sex, LGT can prevent the accumulation of deleterious mutations predicted by Mullers ratchet for asexual populations. This similarity between sex and LGT raises the question why did eukaryotes abandon LGT in favor of sexual reproduction? Understanding the limitations of LGT provides insight into this evolutionary transition. We model the evolution of a haploid population undergoing LGT at a rate{lambda} and subjected to a mutation rate . We take into account recombination length, L, and genome size, g, neglected by previous theoretical models. We confirm that LGT counters Mullers ratchet by reducing the rate of fixation of deleterious mutations in small genomes. We then demonstrate that this beneficial effect declines rapidly with genome size. Populations with larger genomes are subjected to a faster rate of fixation of deleterious mutations and become more vulnerable to stochastic frequency fluctuations. Mullers ratchet therefore generates a strong constraint on genome size. Importantly, we show that the degeneration of larger genomes can be resisted by increases in the recombination length, the average number of contiguous genes drawn from the environment for LGT. Large increases in genome size, as in early eukaryotes, are only possible as L reaches the same order of magnitude as g. This requirement for recombination across the whole genome can explain the strong selective pressure towards the evolution of sexual cell fusion and reciprocal recombination during early eukaryotic evolution - the origin of meiotic sex.

evolutionary biology↗

bioRxiv2020

CO2 reduction driven by a pH gradient

All life on Earth is built of organic molecules, so the primordial sources of reduced carbon are a major open question in studies of the origin of life. A variant of the alkaline-vent theory suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog--and proposed evolutionary predecessor--of the modern Wood-Ljungdahl acetyl-Co-A pathway of extant archaea and bacteria. The first energetic bottleneck of the pathway involves the endergonic reduction of CO2 with H2 to formate, which has proven elusive in low-temperature abiotic settings. Here we show the reduction of CO2 with H2 at moderate pressures (1.5 bar), driven by microfluidic pH gradients across inorganic Fe(Ni)S precipitates. Isotopic labelling with 13C confirmed production of formate. Separately, deuterium (2H) labelling indicated that electron transfer to CO2 did not occur via direct hydrogenation with H2. Instead, freshly deposited Fe(Ni)S precipitates appear to facilitate electron transfer in an electrochemical-cell mechanism with two distinct half-reactions. Decreasing the pH gradient significantly, or removing either H2 or the precipitate, yielded no detectable product. Our work demonstrates the feasibility of spatially separated, yet electrically coupled geochemical reactions as drivers of otherwise endergonic processes. Beyond corroborating the ability of early-Earth alkaline hydrothermal systems to couple carbon reduction to hydrogen oxidation through geologically plausible and biologically relevant mechanisms, these results may also be of significance for industrial and environmental applications, where other redox reactions could be facilitated using similarly mild approaches.

biochemistry↗