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Sex Cells: Meiosis at the centromere (of life science research)

Plants, animals, microbes and more all do it (sex that is), and whether selfish or otherwise (probably selfish), the processes before, during and after meiosis are of incredible interest to study for a huge range of biological applications.

April 04, 2018

At the end of the successful Meiosis and Beyond workshop at Earlham Institute, it was clear how varied and encompassing research into meiosis really is. The story of evolution, for plants, animals, fungi and their parasites, begins with recombination - but the story doesn’t stop there. What can we hope to untangle (other than chromosomes) in the future?

Sex cells.

When I used to think of meiosis, it was always a matter of mechanics - a means to a new beginning. Recombination between chromosomes led to sex cells with (half of) a slightly reshuffled genetic pack, pairs of chromosomes mixed, matched and boxed off into different eggs and sperm.

After this workshop, I learned that, clearly, there’s much more to it than that, and that meiosis underpins many themes in the biological sciences.

Plants, animals, microbes and more all do it (sex that is), and whether selfish or otherwise (probably selfish), the processes before, during and after meiosis are of incredible interest to study for a huge range of biological applications.

Simone Immler, co-organiser of the workshop, kicked off the meeting by surveying the range of research areas represented by the attendees, which highlighted just how broad a topic this is.

Animals, plants, microbes, evolutionary genomics, developmental genomics, clinical research, conservation genomics and cell biology (to name but a few).

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Then again, sex is a pretty selfish act in the first place, as any student of meiosis can attest.

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Selfish sex.

One big topic in meiosis is in sex determination - a subject of great interest to animal breeders, who might want a greater skew of females when it comes to dairy farming of cattle but more males when rearing bovines for steak. On the other hand, a pig farmer would prefer a succulent sow, rather than a chewy male.

Roberta Bergero of the University of Edinburgh gave a great insight into why sex matters in guppies, particularly how her research is informing the variance in meiosis between the sexes.

Linking traits to chromosomes, it’s clear that certain characteristics are passed on only from father to son - think of the colouration of many fish species, for example. There are many examples of sex-derived phenotypes, many of which are still only just being unravelled.

Another look at the peculiarities of meiosis between the sexes was delivered in the introductory talk given by Alexander Sung-Jae Suh of Uppsala University in Sweden, who presented the selfish elements in the W chromosomes of female birds.

These chromosomes are packed full of repetitive transposons, jumping genetic elements implanted by historic retroviruses, a characteristic shared by chickens and birds of paradise alike. Interestingly, these elements seem to want to drift to the sex chromosome, as they’re not as abundant in others, which raises interesting questions about their role.

There’s also another strange chromosome in zebra finches, either rare or just not known about, that is also known to be in another bird species and the lamprey. This “germline restricted chromosome” is present in two copies in female birds, has active gene expression only in this diploid state and survives meiosis only in females. Thus, only females pass it on. It can be present in males but only one copy, which seemingly just sits there.

It’s an interesting chromosome to study for the simple fact that it’s massive, rare and also highly repetitive - perhaps aiding research into what these selfish genetic elements are doing.

Then again, sex is a pretty selfish act in the first place, as any student of meiosis can attest. Claudia Rathje of the University of Kent filled us in on more of this, with tales of the “arms race” between genes on the X and Y chromosomes in sex ratio skewing - highlighting Dawkins’ concept of the “Selfish Gene” quite exquisitely.

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...one of the vessels of the staggeringly wonderful biodiversity that we see all around us.

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Potent parasites.

Turns out parasites are at it, too. Susanne Franssen of the Sanger Institute gave us the low-down on weird meiosis in Leishmania - the flesh eating protozoans found in tropical environments that spread by biting sand flies and kill up to 60 000 people each year and is really hard to get rid of, requiring chemotherapy.

Weird meiosis in this case is namely aneuploidy, which is when cells have an unusual number of chromosomes - which causes a number of conditions in humans, most famously Down’s syndrome. However, while aneuploidy is often lethal to multicellular life, it seems as though it might be quite handy in Leishmania, allowing the parasite to potentially survive tricky environmental changes.

It’s interesting to study mainly because aneuploidy may well be the norm in Leishmania, which raises interesting questions about how chromosomes are inherited - and might yield interesting information about the parasite itself, and how it manages to negotiate the changes that come with “jumping ship”, so to speak, from sand flies to people so effectively, causing such a great nuisance to human life.

Other parasites give farmers a headache, especially those with drug resistance, such as helminths, which also affect people. Hookworm, for one, is a nasty parasite that no-one wants and may be getting harder to get rid of.

Drug resistance in these parasites is inherited, therefore looking at how they have sex makes a lot of sense when trying to understand how populations become less sensitive to drugs down the family line - and understanding these processes in animals is key to understanding processes in humans, too, as is often the case.

Ruminants are an important economical and food concern, too, which is why Stephen Doyle is looking at meiosis for clues to drug resistance in two common parasites of domestic farm animals, Haemonchus contortus and Teladorsagia circumcincta, at the Sanger Institute.

Hookworm, for one, is a nasty parasite that no-one wants and may be getting harder to get rid of. Credit: Jarun Ontakrai, Shutterstock

Helminths

Meiotic madness.

Meiosis itself is pretty mad, when you think about it - and is one of the vessels of the staggeringly wonderful biodiversity that we see all around us. Unravelling the mechanisms around it is a fascinating area of research in its own right.

Aneuploidy in Leishmania gives weird and pretty variable shuffling of chromosomes, which is something of a problem in many plants, too - though in this case the problem is polyploidy, where plants have more than one genome due to hybridisation events. Wheat, for example, has three genomes, making it hexaploid and not diploid like us.

Kirsten Bomblies of JIC looks at meiosis in polyploid relatives of the common research plant Arabidopsis, essentially because it’s “a major hurdle for early polyploids”, which get a bit confused and tangled up when it comes to recombining their abundant chromosomes, literally.

Kirsten studies what genes might contribute to untangling this problem in tetraploids by comparing them with closely related diploids, which offers interesting insights into the mechanisms of meiosis.

And getting to the very nuts and bolts of it all, unravelling how and where DNA is mixed and matched is a fundamental aspect of meiosis research. Where are those double strand breaks happening, why and how are they linked?

We know what happens, on the whole, but how, where and why is still an open research question.

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And getting to the very nuts and bolts of it all, unravelling how and where DNA is mixed and matched is a fundamental aspect of meiosis research.

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Credit: Chayakorn lotongkum/Shutterstock.com

Thoughts for the future.

With all of this abundant expertise across many fields of meiosis research, it was a great time to discuss what the missing ingredients are for meiosis research, and what the future might look like.

In terms of topics to focus on, genome reconfiguration and changes over time came up - how and what are they? In what ways can we quantify mutational mechanisms? What is biologically relevant and what is noise? Is “noise” even noise, for that matter?

And what about recombination rates - how are crossover versus non crossover events determined? What more can we learn about segregation mechanisms?

Raheleh Rahbari of the Sanger Institute has been investigating why older men provide sperm with more mutations, linking many of these to signatures found in cancer; whatever is going on in somatic cells is, apparently, also going on in gonads.

Much of what might be done focused on technologies and how they can be applied, an area under particular focus being the relatively new field of single cell sequencing, which has incredible applications when looking at the differences between sex cells. Imagine what we could find out from sequencing all of the different sperm in a single sperm sample alone.

Along with this comes requirements for more accurate single cell sequencing, as well as non-disruptive methods of imaging and analysing cells, and in vitro system for gametogenesis.

Answering these questions is becoming more possible in an era of multi-omics, third generation sequencing technologies, open science and collaboration. Through community building efforts and workshops such as these, it is easier to understand what needs to be explored, as well as how we can work together to add volumes to the weight of scientific knowledge.

Article author

Peter Bickerton

Scientific Communications & Outreach Manager