Publications by year
In Press
Wotton KR (In Press). Annotation files for the marmalade hoverfly (Episyrphus balteatus) genome.
Abstract:
Annotation files for the marmalade hoverfly (Episyrphus balteatus) genome
Gene annotation file in gtf format and repeats annotation file in bed format. Gene annotation file includes gene_id; transcript_id; gene_name (Drosophila=Human BLAST hit) and gene_description. Protein-coding gene models from Augustus were named EBAG0xxxxxx, non-coding RNA gene models EBAG1xxxxxx and Stringtie RNAseq based ones EBAG2xxxxxx. For details see: Genome-wide transcriptomic changes reveal the genetic pathways involved in insect migration” by Doyle et al. The sequence datasets associated with this annotation have been deposited at DDBJ/ENA/GenBank and are available via Bioproject PRJNA720810. The genome assembly described in this paper has been deposited under the accession JAGTYB000000000. The version described in the above paper is version JAGTYB010000000.
Doyle et al (2022) Genome-wide transcriptomic changes reveal the genetic pathways involved in insect migration. Molecular Ecology.
Abstract.
Wotton KR (In Press). Supporting information: Hawkes et al. (2022) Huge spring migrations of insects from the Middle East to Europe.
Abstract:
Supporting information: Hawkes et al. (2022) Huge spring migrations of insects from the Middle East to Europe
From: Hawkes et al. (2022) Huge spring migrations of insects from the Middle East to Europe: quantifying the migratory assemblage and ecosystem services
Abstract.
2023
Hawkes WL, Davies K, Weston S, Moyes K, Chapman JW, Wotton KR (2023). Bat activity correlated with migratory insect bioflows in the Pyrenees.
Royal Society Open Science,
10(8).
Abstract:
Bat activity correlated with migratory insect bioflows in the Pyrenees
. High altitude mountain passes in the Pyrenees are known to be important migratory hotspots for autumn migrating insects originating from large swathes of northern Europe. In the Pyrenees, prior research has focused on diurnal migratory insects. In this study, we investigate the nocturnal component of the migratory assemblage and ask if this transient food source is also used by bat species. Three seasons of insect trapping revealed 66 species of four different orders, 90% of which were Noctuid moths, including the destructive pest
. Helicoverpa armigera
. otherwise known as the cotton bollworm. Acoustic bat detectors revealed that high activity of
. Nyctalus
. spp. and
. Tadarida teniotis
. bats were closely synchronized with the arrival of the migratory moths, suggesting this food source is important for both resident and migratory bats to build or maintain energy reserves. Bats of the
. Nyctalus
. spp
.
. are likely migrating through the study site using fly-and-forage strategies or stopping over in the area, while resident
. T. teniotis
. may be exploiting the abundant food source to build fat stores for hibernation. This study shows that nocturnal migratory insects are abundant in the Pyrenees during autumn and interact during migration, not only with their co-migrant bats but also with resident bat species.
.
Abstract.
Hawkes WL, Ozden O, Foster O, Walliker T, Lacey K, Gao B, Chapman JW, Wotton KR (2023). High mortality of beetle migrants along the Eastern Mediterranean Flyway.
INSECT CONSERVATION AND DIVERSITY Author URL.
Massy R, Wotton KR (2023). The efficiency of varying methods and degrees of time compensation for the solar azimuth.
Biol Lett,
19(11).
Abstract:
The efficiency of varying methods and degrees of time compensation for the solar azimuth.
Daytime migrants are known to orientate using the position of the sun, compensating for its changing position throughout the day with a 'time-compensated sun compass'. This compass has been demonstrated in many migratory species, with various degrees of accuracy for the actual movement of the sun. Here, we present a model for differing levels of compensation for the solar ephemeris that shows that a high degree of efficiency, in terms of distance travelled, can be achieved without full time compensation. In our model, compensating for the sun's position had a diminishing return with an accuracy of 80% leading to only a 2% reduction in distance travelled. We compare various modes of time compensation-full, partial, time averaged and step-revealing their directional efficiency in terms of distance travelled under an autumn migration scenario. We find that the benefit of time compensation varies with latitude, with time averaging performing very well, especially at all high latitudes, but step compensation performing better at very low latitudes. Importantly, even rudimentary adjustment can dramatically increase the efficiency of migration, which suggests an easy pathway for the independent evolution of time compensation.
Abstract.
Author URL.
Hawkes WLS, Wotton KR (2023). The genome sequence of the Batman Hoverfly, Myathropa florea (Linnaeus, 1758). Wellcome Open Research, 8
Crowley LM, Mitchell R, Doyle T, Wotton KR (2023). The genome sequence of the Common Snout Hoverfly, Rhingia campestris (Meigen, 1822). Wellcome Open Research, 8
Hawkes WLS, Wotton KR (2023). The genome sequence of the Common Spotted Hoverfly, Eupeodes luniger (Meigen, 1822). Wellcome Open Research, 8
Crowley LM, Poole O, Wotton KR (2023). The genome sequence of the Grey-backed Snout-hoverfly, Rhingia rostrata (Linnaeus, 1758). Wellcome Open Research, 8
Crowley LM, Mitchell R, Lab UOOAWWGA, Lab NHMGA, collective DTOLB, programme WSITOL, collective WSISODP, collective TOLCI, Weston ST, Wotton KR, et al (2023). The genome sequence of the Lesser Hornet Hoverfly, Volucella inanis (Linnaeus, 1758). Wellcome Open Research, 8
Hawkes WL, Sivell O, Wotton KR (2023). The genome sequence of the Marmalade Hoverfly, Episyrphus balteatus (De Geer, 1776). Wellcome Open Research, 8
Sivell D, Sivell O, Lab NHMGA, collective DTOLB, programme WSITOL, collective WSISODP, collective TOLCI, Hawkes WL, Wotton KR, Consortium DTOL, et al (2023). The genome sequence of the Vagrant Hoverfly, Eupeodes corollae (Fabricius, 1794). Wellcome Open Research, 8
Hawkes W, Sivell O, Sivell D, Massy R, Wotton KR (2023). The genome sequence of the pied hoverfly, Scaeva pyrastri (Linnaeus, 1758). Wellcome Open Research, 8
Hawkes WLS, Wotton KR (2023). The genome sequence of the slender grass hoverfly, Melanostoma scalare (Fabricius, 1794). Wellcome Open Research, 8
Hawkes WL, Doyle T, Massy R, Weston S, Davies K, Cornelius E, Collier C, Chapman JW, Reynolds DR, Wotton K, et al (2023). The most remarkable migrants – systematic analysis of the Western European insect flyway at a Pyrenean mountain pass.
2022
Doyle T, Jimenez-Guri E, Hawkes WLS, Massy R, Mantica F, Permanyer J, Cozzuto L, Hermoso Pulido T, Baril T, Hayward A, et al (2022). Genome-wide transcriptomic changes reveal the genetic pathways involved in insect migration.
Mol Ecol,
31(16), 4332-4350.
Abstract:
Genome-wide transcriptomic changes reveal the genetic pathways involved in insect migration.
Insects are capable of extraordinary feats of long-distance movement that have profound impacts on the function of terrestrial ecosystems. The ability to undertake these movements arose multiple times through the evolution of a suite of traits that make up the migratory syndrome, however the underlying genetic pathways involved remain poorly understood. Migratory hoverflies (Diptera: Syrphidae) are an emerging model group for studies of migration. They undertake seasonal movements in huge numbers across large parts of the globe and are important pollinators, biological control agents and decomposers. Here, we assembled a high-quality draft genome of the marmalade hoverfly (Episyrphus balteatus). We leveraged this genomic resource to undertake a genome-wide transcriptomic comparison of actively migrating Episyrphus, captured from a high mountain pass as they flew south to overwinter, with the transcriptomes of summer forms which were non-migratory. We identified 1543 genes with very strong evidence for differential expression. Interrogation of this gene set reveals a remarkable range of roles in metabolism, muscle structure and function, hormonal regulation, immunity, stress resistance, flight and feeding behaviour, longevity, reproductive diapause and sensory perception. These features of the migrant phenotype have arisen by the integration and modification of pathways such as insulin signalling for diapause and longevity, JAK/SAT for immunity, and those leading to octopamine production and fuelling to boost flight capabilities. Our results provide a powerful genomic resource for future research, and paint a comprehensive picture of global expression changes in an actively migrating insect, identifying key genomic components involved in this important life-history strategy.
Abstract.
Author URL.
Hawkes WLS, Walliker E, Gao B, Forster O, Lacey K, Doyle T, Massy R, Roberts NW, Reynolds DR, Özden Ö, et al (2022). Huge spring migrations of insects from the Middle East to Europe: quantifying the migratory assemblage and ecosystem services.
Ecography,
2022(10).
Abstract:
Huge spring migrations of insects from the Middle East to Europe: quantifying the migratory assemblage and ecosystem services
Migratory insects are a key component of terrestrial ecosystems, but understanding their full contribution is challenging as they are difficult to track, and migration often takes place at high altitude. Migration hotspots offer an exceptional opportunity to study these otherwise indiscernible movements as migration can be visible at ground level; however these events are often also ephemeral and reported only from chance encounters. It is therefore often difficult to fully characterise the range and number of species involved, the drivers of migration or to appreciate the potential interactions and ecological roles of the migrants. Here we pursue field evidence suggesting that the Karpaz peninsula in northeast Cyprus is a suitable location to systematically collect data on migratory insects. In the spring of 2019, using a combination of timed‐counts, migration‐camera traps and netting we documented over 39 million day‐flying insects from eight orders arriving on Cyprus at rates of up to 5900 insects m‐1 min‐1. Mass arrivals were correlated with higher temperatures and easterly winds. Wind direction and normalised vegetation difference index (NDVI) data suggest that these insects had their natal origins in locations including Syria, Iraq and Saudi Arabia. It is estimated that many billions of insects left the coast of the Middle East heading west into Europe during the study period. While the migrant assemblage was diverse, Diptera were by far the most numerous insect order (86%) followed by Lepidoptera (10%). These migrating insects play a range of vital ecological roles including cross‐continental pollination and the transfer of important nutrients. We believe that the very infrequently explored processes described in this manuscript have important consequences for ecosystems in the destinations of these migratory insects across Europe.
Abstract.
Hawkes WLS, Weston ST, Cook H, Doyle T, Massy R, Guri EJ, Jimenez REW, Wotton KR (2022). Migratory hoverflies orientate north during spring migration.
Hawkes WL, Weston ST, Cook H, Doyle T, Massy R, Guri EJ, Wotton Jimenez RE, Wotton KR (2022). Migratory hoverflies orientate north during spring migration.
Biol Lett,
18(10).
Abstract:
Migratory hoverflies orientate north during spring migration.
Migratory hoverflies are long-range migrants that, in the Northern Hemisphere, move seasonally to higher latitudes in the spring and lower latitudes in the autumn. The preferred migratory direction of hoverflies in the autumn has been the subject of radar and flight simulator studies, while spring migration has proved to be more difficult to characterize owing to a lack of ground observations. Consequently, the preferred migratory direction during spring has only been inferred from entomological radar studies and patterns of local abundance, and currently lacks ground confirmation. Here, during a springtime arrival of migratory insects onto the Isles of Scilly and mainland Cornwall, UK, we provide ground proof that spring hoverfly migrants have an innate northward preference. Captured migratory hoverflies displayed northward vanishing bearings when released under sunny conditions under both favourable wind and zero-wind conditions. In addition, and unlike autumn migrants, spring individuals were also able to orientate when the sun was obscured. Analysis of winds suggests an origin for insects arriving on the Isles of Scilly as being in western France. These findings of spring migration routes and preferred migration directions are likely to extend to the diverse set of insects found within the western European migratory assemblage.
Abstract.
Author URL.
Mantica F, Iñiguez LP, Marquez Y, Permanyer J, Torres-Mendez A, Cruz J, Franch-Marro X, Tulenko F, Burguera D, Bertrand S, et al (2022). Pervasive evolution of tissue-specificity of ancestral genes differentially shaped vertebrates and insects.
Hawkes W, Wotton K, University of Oxford and Wytham Woods Genome Acquisition Lab, Darwin Tree of Life Barcoding collective, Wellcome Sanger Institute Tree of Life programme, Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective, Tree of Life Core Informatics collective, Darwin Tree of Life Consortium (2022). The genome sequence of the dumpy grass hoverfly, <i>Melanostoma mellinum</i> (Linnaeus, 1758).
Wellcome open research,
7Abstract:
The genome sequence of the dumpy grass hoverfly, Melanostoma mellinum (Linnaeus, 1758).
We present a genome assembly from an individual male Melanostoma mellinum (the dumpy grass hoverfly; Arthropoda; Insecta; Diptera; Syriphidae). The genome sequence is 731 megabases in span. The majority of the assembly (99.67%) is scaffolded into five chromosomal pseudomolecules, with the X and Y sex chromosomes assembled. The complete mitochondrial genome was also assembled and is 16.1 kilobases in length.
Abstract.
Hawkes W, Wotton K, Lab UOOAWWGA, collective DTOLB, programme WSITOL, collective WSISODP, collective TOLCI, Consortium DTOL (2022). The genome sequence of the dumpy grass hoverfly, Melanostoma mellinum (Linnaeus, 1758). Wellcome Open Research, 7
Hawkes W, Wotton K (2022). The genome sequence of the plain-faced dronefly, Eristalis arbustorum (Linnaeus, 1758). Wellcome Open Research, 7
2021
Walliker T (2021). Bird and Insect migration through Cyprus and the eastern Mediterranean region.
Abstract:
Bird and Insect migration through Cyprus and the eastern Mediterranean region
Twice each year, vast numbers of birds and insects undergo poleward migrations. Species which cross between Europe and Africa must negotiate traversing the Mediterranean region. Many birds are known to avoid crossing seas and therefore in the east they bypass the Mediterranean by taking an overland route and migrating through Israel, Lebanon and Syria. However, some birds do make the sea crossing and use Cyprus as a steppingstone between Africa and Europe. Despite widespread knowledge of this route, no dedicated studies on bird migration have been carried out in the north of Cyprus, and no season-long assessments of insect migrants has been carried out on the island. From March through to May of 2019, a team of five University of Exeter students surveyed insect and bird spring migration occurring through the northeast peninsular of Cyprus over a 39-day period; this survey was to be repeated in spring 2020, but the COVID-19 pandemic rendered fieldwork impossible. In Chapter 1 observations of bird migration on Cyprus were contextualised by comparing them with ornithological radar data from Israel (a known migratory hotspot), then assessing broad migration trends and the effect of wind on bird migration intensity. In agreement with existing studies, larger birds like raptors were less impacted by wind currents than smaller birds such as songbirds. Moreover, when beneficial tailwinds were scarce, songbirds chose to migrate in lower wind speeds. Migration traffic rates for day-migrating birds were found to be proportionally greater over the Karpaz peninsular than in the Hula valley of Israel. Thirdly, temporal migration patterns for raptors over Cyprus and Israel correlated significantly. Chapter 2 takes a natural history focus by detailing the taxonomic assemblages of migrants recorded on Cyprus, and then discussing the implications of our findings. Higher than expected numbers of migrating crag martins (Ptyonoprogne rupestris), common kestrels (Falco tinnunculus) and pallid harriers (Circus macrourus) for Cyprus were recorded during our spring survey. Observed numbers for pallid harriers suggest that the Karpaz peninsular may possibly be Europe’s most significant flyway for the species. These provisional findings are of great conservation importance as pallid harriers are listed as a globally near threatened species on the IUCN Redlist. In addition, the first African migrant butterfly (Catopsilia florella) on Cyprus since 1986 and the first ever Cyprus record of the ladybird Harmonia quadripunctata were recorded. Furthermore, evidence of mass migratory behaviour in the flies Delia platura and Stomoxys calcitrans is presented, both of which were not previously considered migratory. Observations of signs of illegal bird trapping at the Cyprus study sites is discussed anecdotally.
Abstract.
Massy R, Hawkes WLS, Doyle T, Troscianko J, Menz MHM, Roberts NW, Chapman JW, Wotton KR (2021). Hoverflies use a time-compensated sun compass to orientate during autumn migration.
Proceedings of the Royal Society B: Biological Sciences,
288(1959), 20211805-20211805.
Abstract:
Hoverflies use a time-compensated sun compass to orientate during autumn migration
The sun is the most reliable celestial cue for orientation available to daytime migrants. It is widely assumed that diurnal migratory insects use a ‘time-compensated sun compass’ to adjust for the changing position of the sun throughout the day, as demonstrated in some butterfly species. The mechanisms used by other groups of diurnal insect migrants remain to be elucidated. Migratory species of hoverflies (Diptera: Syrphidae) are one of the most abundant and beneficial groups of diurnal migrants, providing multiple ecosystem services and undergoing directed seasonal movements throughout much of the temperate zone. To identify the hoverfly navigational strategy, a flight simulator was used to measure orientation responses of the hoverfliesScaeva pyrastriandScaeva seleniticato celestial cues during their autumn migration. Hoverflies oriented southwards when they could see the sun and shifted this orientation westward following a 6 h advance of their circadian clocks. Our results demonstrate the use of a time-compensated sun compass as the primary navigational mechanism, consistent with field observations that hoverfly migration occurs predominately under clear and sunny conditions.
Abstract.
Ebdon S, Mackintosh A, Hayward A, Wotton K, Darwin Tree of Life Barcoding collective, Wellcome Sanger Institute Tree of Life programme, Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective, Tree of Life Core Informatics collective, Darwin Tree of Life Consortium (2021). The genome sequence of the clouded yellow, <i>Colias crocea</i> (Geoffroy, 1785).
Wellcome open research,
6Abstract:
The genome sequence of the clouded yellow, Colias crocea (Geoffroy, 1785).
We present a genome assembly from an individual female Colias crocea (also known as Colias croceus; the clouded yellow; Arthropoda; Insecta; Lepidoptera; Pieridae). The genome sequence is 325 megabases in span. The complete assembly is scaffolded into 32 chromosomal pseudomolecules, with the W and Z sex chromosome assembled. Gene annotation of this assembly on Ensembl has identified 13,803 protein coding genes.
Abstract.
Ebdon S, Mackintosh A, Hayward A, Wotton K, collective DTOLB, programme WSITOL, collective WSISODP, collective TOLCI, Consortium DTOL (2021). The genome sequence of the clouded yellow, Colias crocea (Geoffroy, 1785). Wellcome Open Research, 6
Hawkes W, Wotton K (2021). The genome sequence of the drone fly, Eristalis tenax (Linnaeus, 1758). Wellcome Open Research, 6
Hawkes W, Wotton K, University of Oxford and Wytham Woods Genome Acquisition Lab, Darwin Tree of Life Barcoding collective, Wellcome Sanger Institute Tree of Life programme, Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective, Tree of Life Core Informatics collective, Darwin Tree of Life Consortium (2021). The genome sequence of the tapered dronefly, <i>Eristalis pertinax</i> (Scopoli, 1763).
Wellcome open research,
6Abstract:
The genome sequence of the tapered dronefly, Eristalis pertinax (Scopoli, 1763).
We present a genome assembly from an individual male Eristalis pertinax (the tapered dronefly; Arthropoda; Insecta; Diptera; Syriphidae). The genome sequence is 487 megabases in span. The majority of the assembly (95.23%) is scaffolded into seven chromosomal pseudomolecules, with the X and Y sex chromosomes assembled. The complete mitochondrial genome was also assembled and is 17.2 kilobases in length.
Abstract.
Hawkes W, Wotton K (2021). The genome sequence of the tapered dronefly, Eristalis pertinax (Scopoli, 1763). Wellcome Open Research, 6
Hawkes W, Wotton K, Lab UOOAWWGA, collective DTOLB, programme WSITOL, collective WSISODP, collective TOLCI, Consortium DTOL (2021). The genome sequence of the tapered dronefly, Eristalis pertinax (Scopoli, 1763). Wellcome Open Research, 6
Hawkes W, Wotton K, Smith M, University of Oxford and Wytham Woods Genome Acquisition Lab, Natural History Museum Genome Acquisition Lab, Darwin Tree of Life Barcoding collective, Wellcome Sanger Institute Tree of Life programme, Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective, Tree of Life Core Informatics collective, Darwin Tree of Life Consortium, et al (2021). The genome sequence of the two-banded wasp hoverfly, <i>Chrysotoxum bicinctum</i> (Linnaeus, 1758).
Wellcome open research,
6Abstract:
The genome sequence of the two-banded wasp hoverfly, Chrysotoxum bicinctum (Linnaeus, 1758).
We present a genome assembly from an individual female Chrysotoxum bicinctum (the two-banded wasp hoverfly; Arthropoda; Insecta; Diptera; Syriphidae). The genome sequence is 913 megabases in span. The majority of the assembly (98.81%) is scaffolded into five chromosomal pseudomolecules, with the X sex chromosome assembled.
Abstract.
Hawkes W, Wotton K, Smith M, Lab UOOAWWGA, Lab NHMGA, collective DTOLB, programme WSITOL, collective WSISODP, collective TOLCI, Consortium DTOL, et al (2021). The genome sequence of the two-banded wasp hoverfly, Chrysotoxum bicinctum (Linnaeus, 1758). Wellcome Open Research, 6
2020
Gao B, Wotton KR, Hawkes WLS, Menz MHM, Reynolds DR, Zhai B-P, Hu G, Chapman JW (2020). Adaptive strategies of high-flying migratory hoverflies in response to wind currents.
Proceedings of the Royal Society B: Biological Sciences,
287(1928), 20200406-20200406.
Abstract:
Adaptive strategies of high-flying migratory hoverflies in response to wind currents
Large migrating insects, flying at high altitude, often exhibit complex behaviour. They frequently elect to fly on winds with directions quite different from the prevailing direction, and they show a degree of common orientation, both of which facilitate transport in seasonally beneficial directions. Much less is known about the migration behaviour of smaller (10–70 mg) insects. To address this issue, we used radar to examine the high-altitude flight of hoverflies (Diptera: Syrphidae), a group of day-active, medium-sized insects commonly migrating over the UK. We found that autumn migrants, which must move south, did indeed show migration timings and orientation responses that would take them in this direction, despite the unfavourability of the prevailing winds. Evidently, these hoverfly migrants must have a compass (probably a time-compensated solar mechanism), and a means of sensing the wind direction (which may be determined with sufficient accuracy at ground level, before take-off). By contrast, hoverflies arriving in the UK in spring showed weaker orientation tendencies, and did not correct for wind drift away from their seasonally adaptive direction (northwards). However, the spring migrants necessarily come from the south (on warm southerly winds), so we surmise that complex orientation behaviour may not be so crucial for the spring movements.
Abstract.
Doyle T, Hawkes WLS, Massy R, Powney GD, Menz MHM, Wotton KR (2020). Pollination by hoverflies in the Anthropocene.
Proceedings of the Royal Society B: Biological Sciences,
287(1927), 20200508-20200508.
Abstract:
Pollination by hoverflies in the Anthropocene
Pollinator declines, changes in land use and climate-induced shifts in phenology have the potential to seriously affect ecosystem function and food security by disrupting pollination services provided by insects. Much of the current research focuses on bees, or groups other insects together as ‘non-bee pollinators’, obscuring the relative contribution of this diverse group of organisms. Prominent among the ‘non-bee pollinators’ are the hoverflies, known to visit at least 72% of global food crops, which we estimate to be worth around US$300 billion per year, together with over 70% of animal pollinated wildflowers. In addition, hoverflies provide ecosystem functions not seen in bees, such as crop protection from pests, recycling of organic matter and long-distance pollen transfer. Migratory species, in particular, can be hugely abundant and unlike many insect pollinators, do not yet appear to be in serious decline. In this review, we contrast the roles of hoverflies and bees as pollinators, discuss the need for research and monitoring of different pollinator responses to anthropogenic change and examine emerging research into large populations of migratory hoverflies, the threats they face and how they might be used to improve sustainable agriculture.
Abstract.
2019
Wotton KR, Boya G, Menz M, Morris R, Ball S, Lim K, Reynolds D, Hu G, Chapman J (2019). Mass Seasonal Migrations of Hoverflies Provide Extensive Pollination and Crop Protection Services. Current Biology, 29(13), 2167-2173.
Menz MHM, Reynolds DR, Gao B, Hu G, Chapman JW, Wotton KR (2019). Mechanisms and Consequences of Partial Migration in Insects. Frontiers in Ecology and Evolution, 7
Menz M, Brown B, Wotton KR (2019). Quantification of migrant hoverfly movements (Diptera: Syrphidae) on the West Coast of North America. Royal Society Open Science, 6
2018
Verd B, Clark E, Wotton K, Janssens H, Jimenez-Guri E, Crombach A, Jaeger J (2018). A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila. PLoS Biology
Jimenez-Guri E, Wotton KR, Jaeger J (2018). tarsal-less is expressed as a gap gene but has no gap gene phenotype in the moth midge Clogmia albipunctata. Royal Society Open Science
2017
Wotton KR, Alcaine-Colet A, Jaeger J, Jiménez-Guri E (2017). Non-canonical dorsoventral patterning in the moth midge Clogmia albipunctata. EvoDevo, 20178:20
2016
Verd B, Clark E, Wotton KR, Janssens H, Jiménez-Guri E, Crombach A, Jaeger J (2016). A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila.
Crombach A, Wotton KR, Jiménez-Guri E, Jaeger J (2016). Gap Gene Regulatory Dynamics Evolve along a Genotype Network.
Mol Biol Evol,
33(5), 1293-1307.
Abstract:
Gap Gene Regulatory Dynamics Evolve along a Genotype Network.
Developmental gene networks implement the dynamic regulatory mechanisms that pattern and shape the organism. Over evolutionary time, the wiring of these networks changes, yet the patterning outcome is often preserved, a phenomenon known as "system drift." System drift is illustrated by the gap gene network-involved in segmental patterning-in dipteran insects. In the classic model organism Drosophila melanogaster and the nonmodel scuttle fly Megaselia abdita, early activation and placement of gap gene expression domains show significant quantitative differences, yet the final patterning output of the system is essentially identical in both species. In this detailed modeling analysis of system drift, we use gene circuits which are fit to quantitative gap gene expression data in M. abdita and compare them with an equivalent set of models from D. melanogaster. The results of this comparative analysis show precisely how compensatory regulatory mechanisms achieve equivalent final patterns in both species. We discuss the larger implications of the work in terms of "genotype networks" and the ways in which the structure of regulatory networks can influence patterns of evolutionary change (evolvability).
Abstract.
Author URL.
2015
Wotton KR, Jiménez-Guri E, Crombach A, Cicin-Sain D, Jaeger J (2015). High-resolution gene expression data from blastoderm embryos of the scuttle fly Megaselia abdita.
Sci Data,
2Abstract:
High-resolution gene expression data from blastoderm embryos of the scuttle fly Megaselia abdita.
Gap genes are involved in segment determination during early development in dipteran insects (flies, midges, and mosquitoes). We carried out a systematic quantitative comparative analysis of the gap gene network across different dipteran species. Our work provides mechanistic insights into the evolution of this pattern-forming network. As a central component of our project, we created a high-resolution quantitative spatio-temporal data set of gap and maternal co-ordinate gene expression in the blastoderm embryo of the non-drosophilid scuttle fly, Megaselia abdita. Our data include expression patterns in both wild-type and RNAi-treated embryos. The data-covering 10 genes, 10 time points, and over 1,000 individual embryos-consist of original embryo images, quantified expression profiles, extracted positions of expression boundaries, and integrated expression patterns, plus metadata and intermediate processing steps. These data provide a valuable resource for researchers interested in the comparative study of gene regulatory networks and pattern formation, an essential step towards a more quantitative and mechanistic understanding of developmental evolution.
Abstract.
Author URL.
Wotton KR, Schubert FR, Dietrich S (2015). Hypaxial muscle: controversial classification and controversial data?.
Results Probl Cell Differ,
56, 25-48.
Abstract:
Hypaxial muscle: controversial classification and controversial data?
Hypaxial muscle is the anatomical term commonly used when referring to all the ventrally located musculature in the body of vertebrates, including muscles of the body wall and the limbs. Yet these muscles had very humble beginnings when vertebrates evolved from their chordate ancestors, and complex anatomical changes and changes in underlying gene regulatory networks occurred. This review summarises the current knowledge and controversies regarding the development and evolution of hypaxial muscles.
Abstract.
Author URL.
Wotton KR, Jiménez-Guri E, Jaeger J (2015). Maternal co-ordinate gene regulation and axis polarity in the scuttle fly Megaselia abdita.
PLoS Genet,
11(3).
Abstract:
Maternal co-ordinate gene regulation and axis polarity in the scuttle fly Megaselia abdita.
Axis specification and segment determination in dipteran insects are an excellent model system for comparative analyses of gene network evolution. Antero-posterior polarity of the embryo is established through systems of maternal morphogen gradients. In Drosophila melanogaster, the anterior system acts through opposing gradients of Bicoid (Bcd) and Caudal (Cad), while the posterior system involves Nanos (Nos) and Hunchback (Hb) protein. These systems act redundantly. Both Bcd and Hb need to be eliminated to cause a complete loss of polarity resulting in mirror-duplicated abdomens, so-called bicaudal phenotypes. In contrast, knock-down of bcd alone is sufficient to induce double abdomens in non-drosophilid cyclorrhaphan dipterans such as the hoverfly Episyrphus balteatus or the scuttle fly Megaselia abdita. We investigate conserved and divergent aspects of axis specification in the cyclorrhaphan lineage through a detailed study of the establishment and regulatory effect of maternal gradients in M. abdita. Our results show that the function of the anterior maternal system is highly conserved in this species, despite the loss of maternal cad expression. In contrast, hb does not activate gap genes in this species. The absence of this activatory role provides a precise genetic explanation for the loss of polarity upon bcd knock-down in M. abdita, and suggests a general scenario in which the posterior maternal system is increasingly replaced by the anterior one during the evolution of the cyclorrhaphan dipteran lineage.
Abstract.
Author URL.
Wotton KR, Jiménez-Guri E, Crombach A, Janssens H, Alcaine-Colet A, Lemke S, Schmidt-Ott U, Jaeger J (2015). Quantitative system drift compensates for altered maternal inputs to the gap gene network of the scuttle fly Megaselia abdita.
Elife,
4Abstract:
Quantitative system drift compensates for altered maternal inputs to the gap gene network of the scuttle fly Megaselia abdita.
The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species. We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae). It combines quantification of gene expression at high spatio-temporal resolution with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics of gap gene expression differ markedly between M. abdita and Drosophila melanogaster, while the output of the system converges to equivalent patterns at the end of the blastoderm stage. Although the qualitative structure of the gap gene network is conserved, there are differences in the strength of regulatory interactions between species. We term such network rewiring 'quantitative system drift'. It provides a mechanistic explanation for the developmental hourglass model in the dipteran lineage. Quantitative system drift is likely to be a widespread mechanism for developmental evolution.
Abstract.
Author URL.
Alcaine-Colet A, Wotton KR, Jimenez-Guri E (2015). Rearing the scuttle fly Megaselia scalaris (Diptera: Phoridae) on industrial compounds: implications on size and lifespan.
PeerJ,
3Abstract:
Rearing the scuttle fly Megaselia scalaris (Diptera: Phoridae) on industrial compounds: implications on size and lifespan.
Megaselia scalaris (Loew, 1866) (Diptera, phoridae) is a cosmopolitan fly species used in forensic science, and has been developed as a laboratory model species. They feed on decaying corpses as well as a wide variety of organic matter, and previous studies have even found them feeding on liquid paint or shoe polish, suggesting the possibility that they could breakdown industrial compounds. To test this possibility, we fed M. scalaris on a variety of industrially obtained materials and found that it was unable to complete its life cycle, dying at the larval stage, with the majority of compounds tested. However, when fed on modeling clay, a substrate that contains starch and inedible compounds, it was able to complete its life cycle. On this diet we observed increased larval development time, decreased pupal development time and a shortened adult life span. Additionally, pupae and adult flies were smaller than control flies. Contrary to previous reports, we find no evidence that M. scalaris is able to survive on modern formulations of liquid paint.
Abstract.
Author URL.
Cicin-Sain D, Pulido AH, Crombach A, Wotton KR, Jiménez-Guri E, Taly J-F, Roma G, Jaeger J (2015). SuperFly: a comparative database for quantified spatio-temporal gene expression patterns in early dipteran embryos.
Nucleic Acids Res,
43(Database issue), D751-D755.
Abstract:
SuperFly: a comparative database for quantified spatio-temporal gene expression patterns in early dipteran embryos.
We present SuperFly (http://superfly.crg.eu), a relational database for quantified spatio-temporal expression data of segmentation genes during early development in different species of dipteran insects (flies, midges and mosquitoes). SuperFly has a special focus on emerging non-drosophilid model systems. The database currently includes data of high spatio-temporal resolution for three species: the vinegar fly Drosophila melanogaster, the scuttle fly Megaselia abdita and the moth midge Clogmia albipunctata. At this point, SuperFly covers up to 9 genes and 16 time points per species, with a total of 1823 individual embryos. It provides an intuitive web interface, enabling the user to query and access original embryo images, quantified expression profiles, extracted positions of expression boundaries and integrated datasets, plus metadata and intermediate processing steps. SuperFly is a valuable new resource for the quantitative comparative study of gene expression patterns across dipteran species. Moreover, it provides an interesting test set for systems biologists interested in fitting mathematical gene network models to data. Both of these aspects are essential ingredients for progress toward a more quantitative and mechanistic understanding of developmental evolution.
Abstract.
Author URL.
2014
Jiménez-Guri E, Wotton KR, Gavilán B, Jaeger J (2014). A staging scheme for the development of the moth midge Clogmia albipunctata.
PLoS One,
9(1).
Abstract:
A staging scheme for the development of the moth midge Clogmia albipunctata.
Model organisms, such as Drosophila melanogaster, allow us to address a wide range of biological questions with experimental rigour. However, studies in model species need to be complemented by comparative studies if we are to fully understand the functional properties and evolutionary history of developmental processes. The establishment of new model organisms is crucial for this purpose. One of the first essential steps to establish a species as an experimental model is to carefully describe its life cycle and development. The resulting staging scheme serves as a framework for molecular studies, and allows us to homologise developmental processes between species. In this paper, we have characterised the life cycle and development of an emerging non-drosophilid dipteran model system: the moth midge Clogmia albipunctata. In particular, we focus on early embryogenesis (cleavage and blastoderm cycles before gastrulation), on formation and retraction of extraembryonic tissues, and on formation of the germ line. Considering the large evolutionary distance between the two species (approximately 250 million years), we find that the development of C. albipunctata is remarkably conserved compared to D. melanogaster. On the other hand, we detect significant differences in morphology and timing affecting the development of extraembryonic tissues and the germ line. Moreover, C. albipunctata shows several heterochronic shifts, and lacks head involution and associated processes during late stages of development.
Abstract.
Author URL.
Wotton KR, Jiménez-Guri E, García Matheu B, Jaeger J (2014). A staging scheme for the development of the scuttle fly Megaselia abdita.
PLoS One,
9(1).
Abstract:
A staging scheme for the development of the scuttle fly Megaselia abdita.
Model organisms, such as Drosophila melanogaster, provide powerful experimental tools for the study of development. However, approaches using model systems need to be complemented by comparative studies for us to gain a deeper understanding of the functional properties and evolution of developmental processes. New model organisms need to be established to enable such comparative work. The establishment of new model system requires a detailed description of its life cycle and development. The resulting staging scheme is essential for providing morphological context for molecular studies, and allows us to homologise developmental processes between species. In this paper, we provide a staging scheme and morphological characterisation of the life cycle for an emerging non-drosophilid dipteran model system: the scuttle fly Megaselia abdita. We pay particular attention to early embryogenesis (cleavage and blastoderm stages up to gastrulation), the formation and retraction of extraembryonic tissues, and the determination and formation of germ (pole) cells. Despite the large evolutionary distance between the two species (approximately 150 million years), we find that M. abdita development is remarkably similar to D. melanogaster in terms of developmental landmarks and their relative timing.
Abstract.
Author URL.
Lours-Calet C, Alvares LE, El-Hanfy AS, Gandesha S, Walters EH, Sobreira DR, Wotton KR, Jorge EC, Lawson JA, Kelsey Lewis A, et al (2014). Evolutionarily conserved morphogenetic movements at the vertebrate head-trunk interface coordinate the transport and assembly of hypopharyngeal structures.
Dev Biol,
390(2), 231-246.
Abstract:
Evolutionarily conserved morphogenetic movements at the vertebrate head-trunk interface coordinate the transport and assembly of hypopharyngeal structures.
The vertebrate head-trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head-trunk interface.
Abstract.
Author URL.
Wotton KR (2014). Heterochronic shifts in germband movements contribute to the rapid embryonic development of the coffin fly Megaselia scalaris. , 2
Wotton KR (2014). Heterochronic shifts in germband movements contribute to the rapid embryonic development of the coffin fly Megaselia scalaris. , 2
Wotton KR (2014). Heterochronic shifts in germband movements contribute to the rapid embryonic development of the coffin fly Megaselia scalaris.
Wotton KR (2014). Heterochronic shifts in germband movements contribute to the rapid embryonic development of the coffin fly Megaselia scalaris.
Arthropod Struct Dev,
43(6), 589-594.
Abstract:
Heterochronic shifts in germband movements contribute to the rapid embryonic development of the coffin fly Megaselia scalaris.
The coffin fly, Megaselia scalaris, is a species of medical and forensic importance and is increasingly being used for the study of genetics. Postmortem interval can be estimated based on the life stage of M. scalaris recovered from corpses, therefore many studies have addressed the duration of each life stage. These studies demonstrate that embryogenesis completes significantly faster in M. scalaris than in the congener Megaselia abdita and faster even than the 24 h needed for Drosophila melanogaster embryogenesis. However, until now it has been unclear if this increased speed is achieved by reducing developmental time across all embryonic stages or by the acceleration of individual stages and processes. Here I use time-lapse imaging to create a staging scheme for M. scalaris embryogenesis. Comparison of stages between D. melanogaster and both Megaselia species reveals that heterochronic shifts, simultaneous morphogenetic movements and compression of individual stages all contribute to the rapid development of M. scalaris.
Abstract.
Author URL.
Fernández-Jaén A, Suela J, Fernández-Mayoralas DM, Fernández-Perrone AL, Wotton KR, Dietrich S, Castellanos MDC, Cigudosa JC, Calleja-Pérez B, López-Martín S, et al (2014). Microduplication 10q24.31 in a Spanish girl with scoliosis and myopathy: the critical role of LBX.
Am J Med Genet A,
164A(8), 2074-2078.
Abstract:
Microduplication 10q24.31 in a Spanish girl with scoliosis and myopathy: the critical role of LBX.
LBX1 plays a cardinal role in neuronal and muscular development in animal models. Its function in humans is unknown; it has been reported as a candidate gene for idiopathic scoliosis. Our goal is to document the first clinical case of a microduplication at 10q24.31 (chr10:102927883-103053612, hg19), affecting exclusively LBX1. The patient, a 12-year-old girl, showed attention problems, dyspraxia, idiopathic congenital scoliosis, and marked hypotrophy of paravertebral muscles. Her paternal aunt had a severe and progressive myopathy with a genetic study that revealed the same duplication. We propose to consider genetic studies, particularly of LBX1, in patients with scoliosis and/or hypotrophy-hypoplasia of paravertebral muscles of unknown etiology.
Abstract.
Author URL.
2013
Jiménez-Guri E, Huerta-Cepas J, Cozzuto L, Wotton KR, Kang H, Himmelbauer H, Roma G, Gabaldón T, Jaeger J (2013). Comparative transcriptomics of early dipteran development.
BMC Genomics,
14Abstract:
Comparative transcriptomics of early dipteran development.
BACKGROUND: Modern sequencing technologies have massively increased the amount of data available for comparative genomics. Whole-transcriptome shotgun sequencing (RNA-seq) provides a powerful basis for comparative studies. In particular, this approach holds great promise for emerging model species in fields such as evolutionary developmental biology (evo-devo). RESULTS: We have sequenced early embryonic transcriptomes of two non-drosophilid dipteran species: the moth midge Clogmia albipunctata, and the scuttle fly Megaselia abdita. Our analysis includes a third, published, transcriptome for the hoverfly Episyrphus balteatus. These emerging models for comparative developmental studies close an important phylogenetic gap between Drosophila melanogaster and other insect model systems. In this paper, we provide a comparative analysis of early embryonic transcriptomes across species, and use our data for a phylogenomic re-evaluation of dipteran phylogenetic relationships. CONCLUSIONS: We show how comparative transcriptomics can be used to create useful resources for evo-devo, and to investigate phylogenetic relationships. Our results demonstrate that de novo assembly of short (Illumina) reads yields high-quality, high-coverage transcriptomic data sets. We use these data to investigate deep dipteran phylogenetic relationships. Our results, based on a concatenation of 160 orthologous genes, provide support for the traditional view of Clogmia being the sister group of Brachycera (Megaselia, Episyrphus, Drosophila), rather than that of Culicomorpha (which includes mosquitoes and blackflies).
Abstract.
Author URL.
Wotton KR, Alcaine Colet A, Jaeger J, Jimenez-Guri E (2013). Evolution and expression of BMP genes in flies.
Dev Genes Evol,
223(5), 335-340.
Abstract:
Evolution and expression of BMP genes in flies.
Bone morphogenetic proteins (BMPs) play key roles in development. In Drosophila melanogaster, there are three BMP-encoding genes: decapentaplegic (dpp), glass bottom boat (gbb) and screw (scw). dpp and gbb are found in all groups of insects. In contrast, the origin of scw via duplication of an ancestral gbb homologue is more recent, with new evidence placing it within the Diptera. Recent studies show that scw appeared basal to the Schizophora, since scw orthologues exist in aschizan cyclorrhaphan flies. In order to further localise the origin of scw, we have utilised new genomic resources for the nematoceran moth midge Clogmia albipunctata (Psychodidae). We identified the BMP subclass members dpp and gbb from an early embryonic transcriptome and show that their expression patterns in the blastoderm differ considerably from those seen in cyclorrhaphan flies. Further searches of the genome of C. albipunctata were unable to identify a scw-like gbb duplicate, but confirm the presence of dpp and gbb. Our phylogenetic analysis shows these to be clear orthologues of dpp and gbb from other non-cyclorrhaphan insects, with C. albipunctata gbb branching ancestrally to the cyclorrhaphan gbb/scw split. Furthermore, our analysis suggests that scw is absent from all Nematocera, including the Bibionomorpha. We conclude that the gbb/scw duplication occurred between the separation of the lineage leading to Brachycera and the origin of cyclorrhaphan flies 200-150 Ma ago.
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Author URL.
Janssens H, Crombach A, Wotton KR, Cicin-Sain D, Surkova S, Lim CL, Samsonova M, Akam M, Jaeger J (2013). Lack of tailless leads to an increase in expression variability in Drosophila embryos.
Dev Biol,
377(1), 305-317.
Abstract:
Lack of tailless leads to an increase in expression variability in Drosophila embryos.
Developmental processes are robust, or canalised: dynamic patterns of gene expression across space and time are regulated reliably and precisely in the presence of genetic and environmental perturbations. It remains unclear whether canalisation relies on specific regulatory factors (such as heat-shock proteins), or whether it is based on more general redundancy and distributed robustness at the network level. The latter explanation implies that mutations in many regulatory factors should exhibit loss of canalisation. Here, we present a quantitative characterisation of segmentation gene expression patterns in mutants of the terminal gap gene tailless (tll) in Drosophila melanogaster. Our analysis provides new insights into the dynamic mechanisms underlying gap gene regulation, and reveals significantly increased variability of gene expression in the mutant compared to the wild-type background. We show that both position and timing of posterior segmentation gene expression domains vary strongly from embryo-to-embryo in tll mutants. This variability must be caused by a vulnerability in the regulatory system which is hidden or buffered in the wild-type, but becomes uncovered by the deletion of tll. Our analysis provides evidence that loss of canalisation in mutants could be more widespread than previously thought.
Abstract.
Author URL.
2012
Crombach A, Wotton KR, Cicin-Sain D, Ashyraliyev M, Jaeger J (2012). Efficient reverse-engineering of a developmental gene regulatory network.
PLoS Comput Biol,
8(7).
Abstract:
Efficient reverse-engineering of a developmental gene regulatory network.
Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms.
Abstract.
Author URL.
Crombach A, Cicin-Sain D, Wotton KR, Jaeger J (2012). Medium-throughput processing of whole mount in situ hybridisation experiments into gene expression domains.
PLoS One,
7(9).
Abstract:
Medium-throughput processing of whole mount in situ hybridisation experiments into gene expression domains.
Understanding the function and evolution of developmental regulatory networks requires the characterisation and quantification of spatio-temporal gene expression patterns across a range of systems and species. However, most high-throughput methods to measure the dynamics of gene expression do not preserve the detailed spatial information needed in this context. For this reason, quantification methods based on image bioinformatics have become increasingly important over the past few years. Most available approaches in this field either focus on the detailed and accurate quantification of a small set of gene expression patterns, or attempt high-throughput analysis of spatial expression through binary pattern extraction and large-scale analysis of the resulting datasets. Here we present a robust, "medium-throughput" pipeline to process in situ hybridisation patterns from embryos of different species of flies. It bridges the gap between high-resolution, and high-throughput image processing methods, enabling us to quantify graded expression patterns along the antero-posterior axis of the embryo in an efficient and straightforward manner. Our method is based on a robust enzymatic (colorimetric) in situ hybridisation protocol and rapid data acquisition through wide-field microscopy. Data processing consists of image segmentation, profile extraction, and determination of expression domain boundary positions using a spline approximation. It results in sets of measured boundaries sorted by gene and developmental time point, which are analysed in terms of expression variability or spatio-temporal dynamics. Our method yields integrated time series of spatial gene expression, which can be used to reverse-engineer developmental gene regulatory networks across species. It is easily adaptable to other processes and species, enabling the in silico reconstitution of gene regulatory networks in a wide range of developmental contexts.
Abstract.
Author URL.
2011
Wotton KR, Shimeld SM (2011). Analysis of lamprey clustered Fox genes: insight into Fox gene evolution and expression in vertebrates.
Gene,
489(1), 30-40.
Abstract:
Analysis of lamprey clustered Fox genes: insight into Fox gene evolution and expression in vertebrates.
In the human genome, members of the FoxC, FoxF, FoxL1, and FoxQ1 gene families are found in two paralagous clusters. One cluster contains the genes FOXQ1, FOXF2, FOXC1 and the second consists of FOXF1, FOXC2, and FOXL1. In jawed vertebrates these genes are known to be expressed in different pharyngeal tissues and all, except FoxQ1, are involved in patterning the early embryonic mesoderm. We have previously traced the evolution of this cluster in the bony vertebrates, and the gene content is identical in the dogfish, a member of the most basally branching lineage of the jawed vertebrates. Here we extend these analyses to jawless vertebrates. Using genomic searches and molecular approaches we have identified homologues of these genes from lampreys. We identify two FoxC genes, two FoxF genes, two FoxQ1 genes and single FoxL1 gene. We examine the embryonic expression of one predominantly mesodermally expressed gene family, FoxC, and the endodermally expressed member of the cluster, FoxQ1. We identified FoxQ1 transcripts in the pharyngeal endoderm, while the two FoxC genes are differentially expressed in the pharyngeal mesenchyme and ectoderm. Furthermore we identify conserved expression of lamprey FoxC genes in the paraxial and intermediate mesoderms. We interpret our results through a chordate-wide comparison of expression patterns and discuss gene content in the context of theories on the evolution of the vertebrate genome.
Abstract.
Author URL.
2009
Wotton KR, Weierud FK, Juárez-Morales JL, Alvares LE, Dietrich S, Lewis KE (2009). Conservation of gene linkage in dispersed vertebrate NK homeobox clusters.
Dev Genes Evol,
219(9-10), 481-496.
Abstract:
Conservation of gene linkage in dispersed vertebrate NK homeobox clusters.
Nk homeobox genes are important regulators of many different developmental processes including muscle, heart, central nervous system and sensory organ development. They are thought to have arisen as part of the ANTP megacluster, which also gave rise to Hox and ParaHox genes, and at least some NK genes remain tightly linked in all animals examined so far. The protostome-deuterostome ancestor probably contained a cluster of nine Nk genes: (Msx)-(Nk4/tinman)-(Nk3/bagpipe)-(Lbx/ladybird)-(Tlx/c15)-(Nk7)-(Nk6/hgtx)-(Nk1/slouch)-(Nk5/Hmx). of these genes, only NKX2.6-NKX3.1, LBX1-TLX1 and LBX2-TLX2 remain tightly linked in humans. However, it is currently unclear whether this is unique to the human genome as we do not know which of these Nk genes are clustered in other vertebrates. This makes it difficult to assess whether the remaining linkages are due to selective pressures or because chance rearrangements have "missed" certain genes. In this paper, we identify all of the paralogs of these ancestrally clustered NK genes in several distinct vertebrates. We demonstrate that tight linkages of Lbx1-Tlx1, Lbx2-Tlx2 and Nkx3.1-Nkx2.6 have been widely maintained in both the ray-finned and lobe-finned fish lineages. Moreover, the recently duplicated Hmx2-Hmx3 genes are also tightly linked. Finally, we show that Lbx1-Tlx1 and Hmx2-Hmx3 are flanked by highly conserved noncoding elements, suggesting that shared regulatory regions may have resulted in evolutionary pressure to maintain these linkages. Consistent with this, these pairs of genes have overlapping expression domains. In contrast, Lbx2-Tlx2 and Nkx3.1-Nkx2.6, which do not seem to be coexpressed, are also not associated with conserved noncoding sequences, suggesting that an alternative mechanism may be responsible for the continued clustering of these genes.
Abstract.
Author URL.
2008
Wotton KR, Weierud FK, Dietrich S, Lewis KE (2008). Comparative genomics of Lbx loci reveals conservation of identical Lbx ohnologs in bony vertebrates.
BMC Evol Biol,
8Abstract:
Comparative genomics of Lbx loci reveals conservation of identical Lbx ohnologs in bony vertebrates.
BACKGROUND: Lbx/ladybird genes originated as part of the metazoan cluster of Nk homeobox genes. In all animals investigated so far, both the protostome genes and the vertebrate Lbx1 genes were found to play crucial roles in neural and muscle development. Recently however, additional Lbx genes with divergent expression patterns were discovered in amniotes. Early in the evolution of vertebrates, two rounds of whole genome duplication are thought to have occurred, during which 4 Lbx genes were generated. Which of these genes were maintained in extant vertebrates, and how these genes and their functions evolved, is not known. RESULTS: Here we searched vertebrate genomes for Lbx genes and discovered novel members of this gene family. We also identified signature genes linked to particular Lbx loci and traced the remnants of 4 Lbx paralogons (two of which retain Lbx genes) in amniotes. In teleosts, that have undergone an additional genome duplication, 8 Lbx paralogons (three of which retain Lbx genes) were found. Phylogenetic analyses of Lbx and Lbx-associated genes show that in extant, bony vertebrates only Lbx1- and Lbx2-type genes are maintained. of these, some Lbx2 sequences evolved faster and were probably subject to neofunctionalisation, while Lbx1 genes may have retained more features of the ancestral Lbx gene. Genes at Lbx1 and former Lbx4 loci are more closely related, as are genes at Lbx2 and former Lbx3 loci. This suggests that during the second vertebrate genome duplication, Lbx1/4 and Lbx2/3 paralogons were generated from the duplicated Lbx loci created during the first duplication event. CONCLUSION: Our study establishes for the first time the evolutionary history of Lbx genes in bony vertebrates, including the order of gene duplication events, gene loss and phylogenetic relationships. Moreover, we identified genetic hallmarks for each of the Lbx paralogons that can be used to trace Lbx genes as other vertebrate genomes become available. Significantly, we show that bony vertebrates only retained copies of Lbx1 and Lbx2 genes, with some Lbx2 genes being highly divergent. Thus, we have established a base on which the evolution of Lbx gene function in vertebrate development can be evaluated.
Abstract.
Author URL.
Wotton KR, Mazet F, Shimeld SM (2008). Expression of FoxC, FoxF, FoxL1, and FoxQ1 genes in the dogfish Scyliorhinus canicula defines ancient and derived roles for Fox genes in vertebrate development.
Dev Dyn,
237(6), 1590-1603.
Abstract:
Expression of FoxC, FoxF, FoxL1, and FoxQ1 genes in the dogfish Scyliorhinus canicula defines ancient and derived roles for Fox genes in vertebrate development.
In the human genome, members of the FoxC, FoxF, FoxL1, and FoxQ1 gene families are found in two paralagous clusters. Here we characterize all four gene families in the dogfish Scyliorhinus canicula, a member of the cartilaginous fish lineage that diverged before the radiation of osteichthyan vertebrates. We identify two FoxC genes, two FoxF genes, and single FoxQ1 and FoxL1 genes, demonstrating cluster duplication preceded the radiation of gnathostomes. The expression of all six genes was analyzed by in situ hybridization. The results show conserved expression of FoxL1, FoxF, and FoxC genes in different compartments of the mesoderm and of FoxQ1 in pharyngeal endoderm and its derivatives, confirming these as ancient sites of Fox gene expression, and also illustrate multiple cases of lineage-specific expression domains. Comparison to invertebrate chordates shows that the majority of conserved vertebrate expression domains mark tissues that are part of the primitive chordate body plan.
Abstract.
Author URL.
2007
Wotton KR, French KEM, Shimeld SM (2007). The developmental expression of foxl2 in the dogfish Scyliorhinus canicula.
Gene Expr Patterns,
7(7), 793-797.
Abstract:
The developmental expression of foxl2 in the dogfish Scyliorhinus canicula.
The FoxL2 genes are a subfamily of the Fox (forkhead box) gene family. FOXL2 is mutated in the disorder Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome (BPES), which is characterized by eyelid malformations, and Premature Ovarian Failure (POF). In the mouse expression is seen in the perioptic mesenchyme, developing eyelids, ovary and pituitary. We have isolated a foxl2 cDNA from the dogfish Scyliorhinus canicula (also known as the lesser spotted catshark), allowing the characterisation of this gene's sequence and expression from a lineage that diverged early in the evolution of gnathostomes. Molecular phylogenetic analysis strongly grouped this sequence with the gnathostomes within the FoxL2 subfamily. We demonstrate the early expression of Scyliorhinus canicula foxl2 in the mandibular head mesoderm and later in continuous populations of mandibular arch cells and mandibular head mesenchyme cells around the developing pituitary. As development proceeds expression decreases in the mesenchyme of the head but is seen in the mesenchyme around the eye and later in the developing eyelids. Additionally expression is seen in regions of pharyngeal arch mesoderm and in ectoderm from which gill buds will form. This expression is maintained in the developing and elongating gill buds. Thus, S. canicula foxl2 is a marker for the mandibular mesoderm and gill buds and its expression is conserved in the perioptic mesenchyme, developing eyelids and pituitary.
Abstract.
Author URL.
2006
Wotton KR, Shimeld SM (2006). Comparative genomics of vertebrate Fox cluster loci.
BMC Genomics,
7Abstract:
Comparative genomics of vertebrate Fox cluster loci.
BACKGROUND: Vertebrate genomes contain numerous duplicate genes, many of which are organised into paralagous regions indicating duplication of linked groups of genes. Comparison of genomic organisation in different lineages can often allow the evolutionary history of such regions to be traced. A classic example of this is the Hox genes, where the presence of a single continuous Hox cluster in amphioxus and four vertebrate clusters has allowed the genomic evolution of this region to be established. Fox transcription factors of the C, F, L1 and Q1 classes are also organised in clusters in both amphioxus and humans. However in contrast to the Hox genes, only two clusters of paralogous Fox genes have so far been identified in the Human genome and the organisation in other vertebrates is unknown. RESULTS: to uncover the evolutionary history of the Fox clusters, we report on the comparative genomics of these loci. We demonstrate two further paralogous regions in the Human genome, and identify orthologous regions in mammalian, chicken, frog and teleost genomes, timing the duplications to before the separation of the actinopterygian and sarcopterygian lineages. An additional Fox class, FoxS, was also found to reside in this duplicated genomic region. CONCLUSION: Comparison of loci identifies the pattern of gene duplication, loss and cluster break up through multiple lineages, and suggests FoxS1 is a likely remnant of Fox cluster duplication.
Abstract.
Author URL.
2005
Wotton KR, Mazet F, Shimeld SM (2005). Fox gene duplication in vertebrate evolution.
Author URL.