Finding genes that determine variation in sperm morphology and motility
Lead Research Organisation:
University of Sheffield
Department Name: Animal and Plant Sciences
Abstract
Across different animal taxa, sperm are perhaps the most diverse of all types of cell. However, in all species they have one principal function; to fertilise an egg. In many different biological and medical sub-disciplines there has been considerable interest in how sperm morphology can influence sperm motility (swimming speed) and fertility. We probably all have a 'cartoon' image of sperm with the longest tail swimming faster than sperm with short tails. Therefore, it is perhaps surprising that within most organisms where people have looked at the relationship between sperm length and sperm motility they have either failed to find any relationship, or have only found a relationship with particular components of the sperm (e.g. the head, the midpiece). In our study organism, the zebra finch, which is an important model organism in neurobiology and behavioural ecology, we have shown that there is considerable inter-male variation in sperm traits, but that within males sperm morphology and motility are highly repeatable. We have also demonstrated that males with long sperm have the fastest sperm, and that both sperm length and sperm speed are heritable. Finally (and uniquely) we have shown that there is a genetic correlation between sperm length and sperm motility, which strongly suggests that the relationship is causative rather than because both sperm traits are simultaneously influenced by environmental factors (e.g. diet, condition). While investigating zebra finch sperm biology we have also been at the forefront of the development of zebra finch genomics tools. For example, we constructed the first zebra finch genetic linkage map and we were part of an international team that sequenced and assembled the zebra finch genome. In this project we will integrate the two strands (sperm biology and genomics) of our previous zebra finch work. We will perform genome-wide association studies (GWAS) to map and identify the genes responsible for inter-male differences in sperm morphology and motility. Genes responsible for differences in sperm motility have not yet been identified in any species. We will do this by developing a chip that probes 20,000 genetic markers at once and typing 1000 male birds (of known sperm morphology/motility) with the chip. We will also sequence the transcriptome (which contains the part of the genome that encodes proteins) from the testes of 20 males with short sperm and 20 males with long sperm. These males come from our existing selection lines which already show a large difference in sperm length. By integrating the GWAS and the transcriptomics data we will provide the first ever description of the genes that determine variation in sperm morphology and motility. Therefore, our findings will be relevant to researchers in human fertility medicine, animal breeding/agriculture, conservation biology and evolutionary biology.
Technical Summary
The overall aim of this proposal is to identify the genes responsible for variation in sperm traits in the zebra finch. We will do this by employing cutting-edge genomics tools to type 20,000 SNP markers in ~1,000 birds. We will then perform a genome-wide association study (GWAS) to map the genes responsible for inter-male differences in sperm morphology and motility, which are both known to be heritable in our population. The SNPs will be selected from the 1.7M zebra finch SNPs in the public domain and will be chosen to cover the entire genome, while accounting for the heterogeneity in linkage disequilibrium (LD) that we earlier described in the zebra finch genome. The SNPs will be typed using Illumina Infinium beadchips and we will outsource genotyping to an external provider (we recently obtained quotations from 6 UK-based providers). The beadchips will be an essential gene mapping resource to the entire zebra finch genomics community and other users will be able to purchase additional chips. Genotype data will be managed using the PLINK software (which is ideal for quality control checking, summary statistic generation and more sophisticated population genetic tests) and GWAS tests will be performed using EMMAX. The birds we will type are part of our long-running (~20 years) aviary population and most individuals have already been measured for sperm traits. More recently we have established selection lines for long and short sperm, and have seen a strong response to selection, especially in the long-sperm line. Using Illumina sequencing technology we will sequence the testis transcriptome of 20 birds from each of the long and short lines. Gene expression will be compared between the two lines, and we will test for associations between (i) gene expression, (ii) SNPs within the transcriptome and (iii) sperm morphology/motility. These results will be integrated with the GWAS results to provide further dissection of the genetic basis of variation in sperm traits.
Planned Impact
Our project addresses fundamental questions in evolutionary genetics; as such it is largely blue-skies research and will advance understanding of the genetic architecture of quantitative genetic variation. However, the genetics of sperm morphology and motility are of relevance to many areas of biology and medicine and our research has the potential to indirectly make a societal and economic impact. Apart from standard activities (attending conferences, publishing our research, and presenting scientific seminars) we intend to engage in the following impact activities: (i) Computer-assisted semen analysis (CASA) workshop. We will run this workshop immediately after the 2013 Biology of Spermatozoa meeting and hold it in Sheffield. It will be aimed at non-academics that stand to benefit from technology to measure sperm parameters (especially motility). For example, this might include animal breeding/livestock improvement companies, conservation managers/zookeepers and the equine industry. We will also provide training (and scripts) on how to analyse the data using the free statistics software R. Funding is requested to cover travel and subsistence costs. (ii) Training for the Graduate RA and Postdoctoral RA. The University of Sheffield is committed to knowledge exchange and societal/economic impact. The research staff on this project will be given opportunities to develop their understanding and awareness of innovation and the translational skills, with support from the investigators and the Research and Innovation Services officers, and within a broader programme of training. (iii) Outreach We will explain our science to the public via the media, public science events including literary/book festivals and through UCAS visit days. We demonstrate CASA technology to over 1000 visitors to the department every year, showing them video of high and low motility sperm samples. (iv) Creation of a SNP chip The SNP chip we will develop will be commercially available to other users via the provider Illumina, a global company with a UK headquarters.
Organisations
Publications
Assersohn K
(2024)
A sex-linked supergene with large effects on sperm traits has little impact on reproductive traits in female zebra finches
in Proceedings of the Royal Society B: Biological Sciences
Bennison C
(2015)
Long sperm fertilize more eggs in a bird.
in Proceedings. Biological sciences
Bennison C
(2016)
Sperm morphology, adenosine triphosphate (ATP) concentration and swimming velocity: unexpected relationships in a passerine bird.
in Proceedings. Biological sciences
Dawson DA
(2013)
High-utility conserved avian microsatellite markers enable parentage and population studies across a wide range of species.
in BMC genomics
Hemmings NL
(2012)
Inbreeding causes early death in a passerine bird.
in Nature communications
Kim KW
(2017)
A sex-linked supergene controls sperm morphology and swimming speed in a songbird.
in Nature ecology & evolution
Mundy NI
(2016)
Red Carotenoid Coloration in the Zebra Finch Is Controlled by a Cytochrome P450 Gene Cluster.
in Current biology : CB
Mundy, Nicholas I.
(2016)
Red Carotenoid Coloration in the Zebra Finch Is Controlled by a Cytochrome P450 Gene Cluster
Title | Genome Top Trumps |
Description | I created a Genomes card game, based on the popular 'Top Trumps' cards. Each card contains information about the genome of a different species. The cards have been used as an educational tool with the public (schoolchildren) and with undergraduate students. |
Type Of Art | Artefact (including digital) |
Year Produced | 2012 |
Impact | Used during outreach events with the public e.g. University of Sheffield Discovery Night; secondary school STEM clubs. |
Description | We have shown that inter-male differences in sperm morphology and motility are largely genetic. The differences are not caused by a handful of genes of large effect, but instead are caused by many genes, each of small effect. Gene mapping and gene expression studies have shown that a larger than expected proportion of these genes are on the zebra finch Z chromosome, one of the avian sex chromosomes. A list of candidate genes that contribute most to this variation has been identified. We have developed new genomics tools for the zebra finch research community, including a high density single nucleotide polymorphism (SNP) chip with half a million markers, and a zebra finch microarray, suitable for gene expression profiling. Both are commercially available to users, via the company Affymetrix. |
Exploitation Route | The genes we have identified will be of interest to researchers working on sperm biology in other organisms including humans. Birds and mammals share many of the same genes, and it is highly likely that genes that affect spermatogenesis in zebra finches will have similar effects in humans. |
Sectors | Agriculture Food and Drink Environment Healthcare |
Description | We organised and ran a workshop on Computer Assisted Semen Analysis (CASA) to stakeholders from animal management (e.g. zoos) and academic research. The workshop was delivered by the RA employed on this grant, along with an external expert (Prof Gerhard van der Horst). The lead PI also contributed a session on data analysis of CASA parameters. We ran the workshop one day after the Biology of Spermatazoa meeting, ran by co-I Tim Birkhead, to ensure that as many attendees as possible were already in the local area. In 2016 our paper on the mapping of the red locus in birds received widespread media coverage, and featured on many of the world's most well known news web sites and scientific radio broadcasts (e.g. www.bbc.co.uk/news, New York Times, BBC Radio, etc) |
First Year Of Impact | 2016 |
Sector | Agriculture, Food and Drink,Education,Environment,Healthcare |
Impact Types | Societal |
Description | NERC Biomolecular Analysis Facility Pilot Project |
Amount | £5,034 (GBP) |
Funding ID | NBAF1029 |
Organisation | Natural Environment Research Council |
Department | NERC Biomolecular Analysis Facility (NBAF) |
Sector | Public |
Country | United Kingdom |
Start | 11/2016 |
End | 01/2017 |
Title | Zebra finch High density SNP chip |
Description | We developed a high density SNP chip with the provider Affymetrix. The chip was designed to probe around 600,000 genetic markers, of which around 200,000 proved to be polymorphic in our study population. The chip was used to study the genetic architecture of sperm traits, as described in a paper by Kim et al., published in Nature Ecology and Evolution in 2017. |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | No, although the chip is available to other researchers studying zebra finches and can be purchased from Affymetrix. |
URL | https://www.nature.com/articles/s41559-017-0235-2?WT.feed_name=subjects_sexual-selection |
Description | Behind the paper |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I wrote a Blog on Nature Ecology & Evolution community, outlining the main results of our project, in a style that was intended to be accessible yet informative about the underlying science (and the scientific process). |
Year(s) Of Engagement Activity | 2017 |
URL | https://natureecoevocommunity.nature.com/users/55941-jon-slate/posts/18441-a-sex-linked-supergene-co... |
Description | Spoke at public event - Pint Of Science |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Approximately 60 people attended a talk I gave at The Sheffield Tap, as part of the nationwide 'Pint of Science' event. I spoke about the value of long term individual-based studies of animal populations, and why they inspire so many biologists. |
Year(s) Of Engagement Activity | 2017 |
URL | https://pintofscience.co.uk/ |