The Evolutionary Dynamics of Genetic Conflict: the Origin, Maintenance and Loss of Paternal Genome Elimination.

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

Reproduction across the tree of life: Why so many ways of doing it?

During sexual reproduction, two unrelated individuals cooperate to achieve a common goal: pass on their genes to the next generation. This cooperation is however not without conflict, parents can fight over who raises the kids, and partners can cheat and mate with other mates. Despite these conflicts genes of the mother and father are, at least in most animals, equally represented in the offspring. This is, however, not always the case. In my research I study a group of insects whose reproduction is incredibly variable and where evolutionary innovations appear to have reduced the importance of males. For example in the citrus mealybug (a plant parasite) and the human body lice (our own parasite), males are still needed to fertilize females, but the female can eliminate his genes from her son. This unusual type of reproduction called "Paternal Genome Elimination" (PGE) is in the female's interest as her sons will always pass on her genes, instead of those of her partner. I use these two species to study how conflict between the sexes can have lead to the evolution of this strange reproductive behaviour.

I aim to understand how males and females compete by studying the behavior of their genes within their offspring, using a range of state-of-the-art genetic techniques. In mealybugs we know that a father's genes are not simply eliminated from its sons sperm, but also prevented from being expressed. I aim to study the expression of paternal genes in males of both mealybugs and lice to understand if these genes might have the opportunity to fight against their elimination.

The way a father's genes are eliminated from his sons is still unclear, although it seems to take place in the testis while sperm is produced. I aim to study the mechanism of elimination in lice by comparing the process of sperm production in males with and without PGE.

Some of the finest minds in evolutionary biology have theorized about the evolution of PGE, yet to date, none of these theories have been tested empirically. Here I will use the human body louse, in which PGE has only recently been discovered to test these theories. I will use crosses between individuals with and without PGE to study how this trait is inherited and how it can spread though the population.

In most species with PGE it seems that the mother's genes have won and ensured that they are the ones their sons will pass on to his children. This might not always be the case though. In the final project of this proposal I will study a clade of Australian insect, closely related to mealybugs. Previous research suggests that some species have lost PGE and might have reverted back to "normal" reproduction. I will study species across this clade to see how often PGE has been lost and which factors might be responsible.

Taken together, these approaches will address the forces responsible for the evolution of an unusual reproductive system. This knowledge will help scientists understand why reproduction, a process so fundamental, is so variable across life.

Planned Impact

I identify a number of groups of beneficiaries. The proposed project is primary research, as such the primary beneficiaries will be: (1) Academic beneficiaries (for more details see previous section). In addition, we identify a set of beneficiaries that includes both academics and possible commercial partners: (2) The biological control and parasitology community. Finally, we also identify a third set of beneficiaries: (3) The general public.

(1) Academic beneficiaries
This work will make a significant contribution to the field of biology, and will increase the prestige in which the UK scientific community is already perceived. Using an empirical and highly original approach, I will study the importance of genomic conflict, a topic that has generated a lot of interest in the community but which few labs have been able to address empirically. I therefore expect this work to generate considerable interest within the scientific community. Furthermore the proposed project uses state-of-the-art genomics techniques developed by epigenesists, to study insect reproduction in non-model organisms, showing that these techniques are transferable across fields and organisms. Finally, my work has captured the interest of a large number of international collaborators that are attracted by my unique approach. Collaborating with these researchers has introduced me to novel approaches and will allow me to attract international science funding. For example my previous collaborations with US researchers has resulted in a role of senior collaborator on two recently submitted NSF grants. Taken together these approaches, collaborations and expected results will increase my scientific breadth as well as the knowledge base of the UK scientific community.

(2) The biological control and parasitology community
Both of the insects utilized in this proposal have important implications for human wealth and health. 1) Mealybugs are among the most damaging agricultural pests to both crops and ornamentals. Some species can also act as vectors of plant pathogens. Furthermore mealybugs and other scale insects are notoriously hard to control, as they are resistant to many commonly used pesticides and are disproportionately common in invasive faunas. 2) The human body louse is a treat to human health due to its ability to act as a disease vector for typhus and trench and relapsing fever. The infection frequency of this species is on the rise, most likely due to the evolution of insecticide resistance.

Understanding the reproductive biology of pests is important to design successful pest management strategies (see pathways to impact for more details): It affects both the rate at which pests can spread, as well as the rate with which they can evolve insecticide resistance. I therefore expect my research to be of considerable interest to applied entomologist involved in pest control. As such I will regularly communicate with experts on scale insect biocontrol (e.g. Dr. Mike Copland, the director of Wyebugs a UK-based biocontrol company) and louse biology (e.g. Ian Burgess, Director of the Medical Entomology Centre).

(3) The general public.
Unusual reproductive behaviours are of considerable interest to the general public. My previous work was covered widely in the international media (including the New York Times). I aim to continue communicating my research by writing press releases for all my publications in collaboration with the University Press & Information Office. I also aim to deposit all published results into publicly available depositories and am involved in the development and maintenance of a more specific publicly available database: The Nescent funded "Tree of Sex" database (see Pathways to Impact). I will redesign my homepage to make it more accessible to a wide audience and will make the pdf's of my publications available through my website. Finally I aim to publish in open access journals whenever appropriate.

Publications

10 25 50
 
Description The main aim of the fellowship is to understand the evolution of a unusual type of reproduction found in some insects where males silence and subsequently eliminate all genes they inherited from their father (paternal genome elimination). In the first year of my fellowship I have published (in Ecology letters) important theoretical findings that could help explain the phylogenetic distribution of this type of reproduction across the tree of life. I have also conducted preliminary field studies and experiments to study the prevalence and mechanisms responsible for of this type of reproduction in mealybugs, Australian scale insects and in human head/body lice. The first manuscript on human lice was published in 2018. We show, for the first time, that this species reproduces through paternal genome elimination and discuss how this affects the way that traits, such as insecticide resistance are predicted to evolve. This manuscript and the first manuscripts on mealybug reproduction we published in 2019 were the first formal genetic analyses of inheritance patterns in species with PGE and we showed that while males indeed exclude the genes they received from their father from their sperm, this process is "leaky". Apart from focusing on patterns of inheritance we have also studied patterns of expression of maternal and paternal alleles in both lice and mealybugs and found that lice have a regular pattern of gene expression in males, however in mealybugs gene expression is strongly biased to expression from maternal genes. The manuscript on mealybug showing genome wide genomic imprinting in males is now published in Molecular Biology and Evolution. We also have followed up these results in mealybugs by studying the epigenetic modifications responsible for the differential behaviour of maternally and paternally deprived chromosomes and show that DNA methylation plays a key role. One manuscript focusing on sex-specific patterns of methylation is now out in Molecular Ecology, while a second manuscript comparing methylation in mealybug with that in other Arthropods is out in Plos Genetics. Finally together with a collaborator at the university of Queensland in Brisbane we have studied PGE across multiple species of insects and show rapid turnover of patterns of gene expression and are preparing a manuscript describing this pattern
Exploitation Route In terms of academic impact, my work was cited >300x in 2020 and I am regularly invited to give departmental seminars and keynote/invited talks both in the UK and abroad. We have also setup new collaborations with researcher in the UK, US and mainland Europe to continue our work on the evolutionary genomics of unusual reproduction in insects.

In terms of societal impact, our work on lice can help predict the way in which resistance to different pesticides can spread. Our mealybug genomic data is currently being used to design new methods to produce pheromone, a key aspect of biocontrol.
Sectors Agriculture, Food and Drink,Environment

 
Description 15k small research grant
Amount £14,646 (GBP)
Funding ID RG160842 
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2017 
End 03/2018
 
Description ERC starting grant
Amount € 1,494,055 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 01/2019 
End 12/2024
 
Description Institutional Strategic Support Fund
Amount £37,246 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 01/2018
 
Description MacLagan Travel Grant
Amount £1,500 (GBP)
Organisation Royal Society of Edinburgh (RSE) 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2014 
End 04/2015
 
Description Mary Kinross seedcore funding
Amount £8,038 (GBP)
Organisation Mary Kinross Charitable Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2014 
End 09/2015
 
Description PhD studentship
Amount £1 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2014 
End 09/2018
 
Description PhD studentship
Amount £1 (GBP)
Organisation British Society for the History of Science (BSHS) 
Department Darwin Trust of Edinburgh
Sector Charity/Non Profit
Country United Kingdom
Start 08/2014 
End 09/2018
 
Description PhD studentship
Amount £0 (GBP)
Organisation British Society for the History of Science (BSHS) 
Department Darwin Trust of Edinburgh
Sector Charity/Non Profit
Country United Kingdom
Start 09/2016 
End 10/2020
 
Description Royal Society Dorothy Hodgkin fellowship
Amount £573,590 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2019 
End 06/2024
 
Title Mealybugbase ENSEMBL genome database 
Description In collaboration with Mark Blaxter (Edinburgh) and T. McCucheon (Montana) we have developed a genome database to collate datasets for ~10 mealybug species and their symbionts. The database is based upon the ENSEMBL platform and is publically available. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact no impacts reported yet 
URL http://ensembl.mealybug.org/index.html
 
Title tree of sex database 
Description Comparative database of sex determination systems, compiled as part of the Nescent working group "The Tree of Sex" 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact The database and companion paper have been cited 14 times 
URL http://treeofsex.org
 
Description Body lice empirical work 
Organisation University of Massachusetts
Country United States 
Sector Academic/University 
PI Contribution Together with Prof John Clark at the University of Massachusetts Amherst I designed a number of experiments that are conducted by a master students in Prof Clark's lab with genetic analyses done by myself. I am currently analyzing the data and expect to start preparing a manuscript early 2015.
Collaborator Contribution Together with Prof John Clark at the University of Massachusetts Amherst I designed a number of experiments that are conducted by a master students in Prof Clark's lab with genetic analyses done by myself. I am currently analyzing the data and expect to start preparing a manuscript early 2015.
Impact no outcomes have been produced as of yet
Start Year 2013
 
Description Genome elimination in Australian scale insects 
Organisation University of Queensland
Department School of Chemistry and Molecular Biosciences
Country Australia 
Sector Academic/University 
PI Contribution I visited the lab of Dr Lyn Cook twice to analyze samples. My PhD student will go on another visit in May 2017 to finish this analysis and prepare a manuscript
Collaborator Contribution Dr Cook has provided samples and expertise, hosted me in her lab and is cosupervising a PhD student on the project
Impact none as of yet
Start Year 2013
 
Description "How We Do Sex" Blog with Twitter account https://medium.com/how-we-do-sex 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The blog platform releases posts every 1-2 months and intends to educate the general public on the diversity of genetic systems. This platform also welcomes guest posts from researchers and publishes interviews on scientists working on sex determination systems. Some of the posts were shared and retweeted in Twitter and Facebook.
Year(s) Of Engagement Activity 2017,2018
URL https://medium.com/how-we-do-sex
 
Description Café Scientifique. Public lecture on "The wondrously diverse world of animal reproduction and genetics" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact My public lecture attracted 20 members of the public and sparked questions and discussion afterwards
Year(s) Of Engagement Activity 2015
URL http://cafescientifique.org/index.php?option=com_contentbuilder&title=cafe-details-edinburgh&control...
 
Description Media coverage (Radio and print) of our publication on human lice 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact We released a press release on our paper on human lice. As a result we 1) got asked to record a 5-min interview for BBC Radio Scotland Newsdrive describing main findings and answering general questions about louse reproduction and insecticide resistance which was broadcast; 2) interviewed by a journalist for the Daily Mail which resulted in an article in the Scottish Daily Mail.
Year(s) Of Engagement Activity 2018
URL https://www.pressreader.com/uk/scottish-daily-mail/20180129/281539406390352
 
Description NERC ambassador at the London Natural History Museum's 'Science Uncovered' event. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I interacted with the public through several activities including a "speed dating" event
Year(s) Of Engagement Activity 2015
URL http://www.nhm.ac.uk/visit/exhibitions/science-uncovered-2015.html