Sexual selection, condition dependence and meiotic drive

Lead Research Organisation: University College London
Department Name: Genetics Evolution and Environment

Abstract

In many species, females show strong sexual preferences to mate with particular males - those with elaborate and exaggerated sexual ornaments. These traits are thought to be honest signals of male genetic quality. But what is the nature of the "good genes" benefits that females derive from mate preference?

We will address this fundamental question using the stalk-eyed fly, an iconic example of extreme sexually-selected morphological evolution. Male flies have greatly exaggerated eyespan and females prefer to mate with males with the most extreme eyespan. Of great interest, stalk-eyed flies harbour a selfish genetic element on the X chromosome that causes sex-ratio distortion through meiotic drive. In normal male meiosis, the X and Y chromosomes segregate equally into sperm. But the meiotic drive element produces a toxin that attacks the Y chromosome, causing Y-bearing sperm to die. So all sperm contain the drive X chromosome, and only female offspring are produced.

Meiotic drive persists in populations of stalk-eyed flies because of the two-fold advantage the element gains in meiosis (it is passed on to all offspring, whereas other genes are only passed to half the offspring). But its spread is limited because it has overt deleterious effects on the fitness of the organism. Most obviously, it is bad because it kills half of a male's sperm. But it is also bad because the genes causing meiotic drive exist in an "inversion" - a part of the X chromosome that has been flipped around and is orientated in the opposite direction. Inversions cannot undergo normal processes like genetic recombination, and tend to accumulate deleterious mutations.

We hypothesise that females gain benefits from avoiding mating with meiotic drive males, as they have low genetic quality. We will test the prediction that females discriminate against drive males. Preliminary work supports this, as drive males have small eyespan. We will investigate this further by exposing males to a range of environmental stresses that are typical of those experienced in the wild, to test whether the sexual ornament is an "honest" signal of genetic quality, in turn explaining why females use it to select a mate. We will characterise in depth how meiotic drive disrupts fertility (by measuring reproductive organ size, sperm allocation and sperm competition) and survival components of fitness, again under variable environmental stress. An interesting prediction is that the rest of the genome has evolved counter-adaptations to drive that will ameliorate loss of performance. We will investigate evidence for this at both the organismal and genomic levels. Evolutionary responses will be tracked at the sequence level by creating high-quality reference genomes of drive and non-drive chromosomes and investigating genomic signatures of changes that are deleterious or beneficial to fitness. Intensive laboratory experiments will be backed up by extensive field investigations of female mating behaviour and male trait distribution of drive-carrying flies in the wild, and how the frequency of drive varies with environmental stress under field conditions. All these strands contribute to our overarching goal: to show how sexual selection, on males and females, interacts with a chromosomal region with clear deleterious effects on organismal fitness.

Planned Impact

Our findings will be of immediate interest to the private sector and policy makers. In recent years there has been considerable interest in commercialising technology via spin-out companies (Oxitec, for example) to control invasive species and disease insect vectors. One method of control is the development of applied gene-drive technologies which exploit CRISPR gene editing and are a synthetic equivalent of naturally occurring meiotic drive systems. Trials using such constructs are already being used for insect vectors of human disease but it remains unclear how they will fare after release into the environment. Valuable insights can be obtained from the evolutionary behaviour of existing natural meiotic drive systems. In addition, there has been considerable interest from policy makers about the release of synthetic constructs into the wild, especially concerning contamination of natural species, and unforeseen deleterious consequences. There is considerable scope for an effective exchange of ideas and insights between researchers in fundamental research and the applied science community. It is important that commercial approaches take account of any evidence that genomes can respond to the presence of drive by evolving counter-adaptations to reduce impaired host performance. Such responses may act as a brake on the efficacy of synthetic gene-drive technology.

We will use a range of dissemination methods: publishing in front-line open-access journals, research conference presentations, and invited talks to other research groups. These provide the bedrock outputs of our research. They will be all open access and hence readily available. We will place our results in a broader perspective and enhance its impact by organising a one-day workshop: "What do natural drive systems tell us about the prospects of synthetic gene-drive technology?" in mid-year 3 of the project. This event will bring leading academic researchers of naturally occurring drive in a range of species together with leaders in the rapidly growing field of synthetic gene-drive technology, to provide a state-of-the-art review and evaluate future research prospects. We will also invite policy makers interested in the ethical issues surrounding synthetic gene-drive technology. In the longer term, there are exciting opportunities for extensive collaborations and knowledge transfer with the private sector and policy makers via secondments and CASE project development. Progress of the project will be regularly publicised via blogs on our websites.

Our findings will also be of broad interest to a wider community of undergraduates, school pupils and the general public. These communities are fascinated by environmental science in general and have a natural curiosity about sexual selection and the interactions between the sexes. Stalk-eyed flies are especially charismatic exemplars of sexual selection. They appear in many textbooks in evolutionary and ecological science, so the research has broad generality. These communities will benefit from seeing how cutting-edge techniques are used to further advance the UK science base. We will offer summer placements (one per year) to engage undergraduate students midway through their studies. We will contribute to both Institutions Researcher Evenings (aimed at adults) and Discovery Evenings (aimed at children), and to education outreach programmes, fostering contact with local schools and provide several places annually for school pupils to have laboratory placements. Our outreach will involve talks at schools and also the provision of a resource pack aimed at 14-18 year olds and their teachers. The pack will explain our project's use of phenotypic and genetic approaches to understand evolution. Our aim is to foster interest among schoolchildren in science careers.
 
Description 2019
1. Meiotic drive is a genetic disease of males. We are studying it in flies. Drive males have a fertility problem as all their Y-bearing sperm die. So males with drive only have competent X-bearing sperm and hence only produce female offspring (females are XX and males XY).
2. We have shown that adaptive compensation has evolved in drive males - they produce as many sperm per ejacuate as normal males, despite the death of half their sperm.
3. This has prompted further study

2020
4. Paper on adaptive compensation has been published.
5. A further paper on the viability costs of meiotic drive in males and females has been published. This contradicts previous findings on viability and further contradicts previous interpretations of fertility differences. It represents an important finding in the field.
6. A paper on adaptive change in mating behaviour was published showing no direct effect of drive, contrary to prediction. This shows limits to adaptive change relating to the mating ecology.
7. A paper on the evolution of mating types has been published.

2021
8. A review paper on resistance to natural and synthetic drive was published. This was a cooperative paper engaging basic scientists whose investigations are relevant in applied contexts using gene drive technology, meeting the Pathways to Impact objectives of the grant
9. Data was uploaded in agreement with the DMP at the NERC site.
10. A theoretical paper was published on how X-linked drive can have beneficial effects on population persistence, as well as causing extinction when it becomes too common
11. A paper was published on lateral gene transfer in bacteria in contrast to meiotic sex in eukaryotes
12. A paper was published on the structure of the stalk-eyed fly leg and how it generates force for jumping
13. A paper was published which shows that meiotic drive does not cause a condition-dependent loss of sexual ornament size

2022
14. Analysis of field samples is under way. Analysis has been impeded because the postdoc has left.
15. The whole genome sequencing project has been seriously delayed by COVID and close down of the NERC NEOF Sheffield and associated NEOFs. The SR drive genome has been sequenced and a draft genome constructed; the ST wildtype drive genome has been sequenced and is being constructed at the moment. RNAseq samples have been extracted and are being sequenced shortly. This work is severely delayed due to COVID.
16. A PhD student spent 3 months at the Swiss Bioinformatics Institute, Lausanne, developing tools for integrative gene mapping in previously unstudied species. This methodology is being written up. It will then be applied to the stalk-eyed fly data.
Exploitation Route The finding will have relevance to those developing "gene drive" technology for suppressing insect vectors of disease. A review paper on adaptive response to meiotic drive has been published. This allowed engagement with end-users. Further dissemination of the scientific work has been interupted due to Covid, but will be presented at future meetings.
Sectors Agriculture, Food and Drink,Education,Healthcare,Pharmaceuticals and Medical Biotechnology,Other

 
Description The findings were used in a presentation to scientists involved in developing "gene drives" technology in Arolla Switzerland in June 2018. This has led to a joint article being written which hopefully was published in 2020 on resistance to drive. This is an important consideration in the development of this new technology, and places limits on its utility. It is important to understand how resistance develops. My contribution is to study adaptive change to drive, which is slightly different from straight forward resistance, and leads to the greater spread of drive. This is of importance in evaluating the spread of synthetic gene drives. I was invited to submit an article to a special edition of Proceedings of the Royal Society B on "Natural and synthetic gene drive systems" which has been published. A review paper on resistance to natural and synthetic drive was published. This was a cooperative paper engaging basic scientists whose investigations are relevant in applied contexts using gene drive technology, meeting the Pathways to Impact objectives of the grant. COVID has serious disrupted the opportunities to relay this research to a wider audience
First Year Of Impact 2019
Sector Agriculture, Food and Drink,Education,Healthcare,Pharmaceuticals and Medical Biotechnology,Other
Impact Types Societal,Policy & public services

 
Title Data from: Does meiotic drive alter male mate preference? 
Description Data from male mate preference assays 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Paper published doi:10.1093/beheco/arz176 
URL https://datadryad.org/stash/dataset/doi:10.5061/dryad.2f8v175
 
Title Data from: Maintenance of fertility in the face of meiotic drive 
Description These data are from an experiment examining fertility and reproductive organ size of males that do or do not carry sex-ratio meiotic drive. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Paper published https://www.journals.uchicago.edu/doi/pdfplus/10.1086/707372 
URL https://datadryad.org/stash/dataset/doi:10.5061/dryad.088kq34
 
Title Data from: Meiotic drive reduces egg-to-adult viability in stalk-eyed flies 
Description raw egg-to-adult viability data https://doi.org/10.5061/dryad.kc49jk1 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Data analysed in published paper 
URL http://dx.doi.org/10.1098/rspb.2019.1414
 
Description Prof Christophe Dessimoz, tools for gene discovery 
Organisation Swiss Institute of Bioinformatics (SIB)
Country Switzerland 
Sector Charity/Non Profit 
PI Contribution PhD secondment to the Dessimoz lab
Collaborator Contribution Developing tools for gene discovery in un-annotated genomes using the OMA database
Impact None yet. Work being written up
Start Year 2021
 
Description Discussion with author of popular science article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Ancient cells has sex fusion proteins before sex evolved, reporter Jake Buehler, Quanta Magazine
Year(s) Of Engagement Activity 2022
URL https://www.quantamagazine.org/ancient-cells-had-sex-fusion-proteins-long-before-sex-evolved-2022021...
 
Description Provided information for publication 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Helped reporter Majorie Hecht at Current Science Daily write about my eLife paper on control of mitochondrial mutations
Year(s) Of Engagement Activity 2021
URL https://currentsciencedaily.com/stories/608581962-university-college-london-research-team-develops-m...
 
Description Workshop Arolla, Switzerland 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentations, discussion, and article writing as a collective
Year(s) Of Engagement Activity 2018