Dr Natasha Yelina

Introduction

My team studies meiosis - a highly conserved cell division in all sexually reproducing eukaryotes that produces gametes (eggs and sperm). Central and unique to meiosis is crossover recombination where parental chromosomes exchange segments. Crossovers create genetic diversity which underpins evolution, adaptation and selective breeding.

Using plants as a model, my lab combines genetic, proteomic and synthetic biology ‘build-to-understand’ approaches to discover how crossover landscapes are shaped in eukaryotes. In addition to bridging a fundamental knowledge gap, this research has strong potential to expedite crop breeding though engineering crossover landscapes in native and synthetic plant chromosomes.

Current major projects

• What determines crossover positioning?
• Can de novo crossovers be engineered in defined genomic locations?
• How can we expedite (legume) crop genetic improvement?

Detailed research programme

What determines crossover positioning?

Crossovers are rare (1-3 per chromosome per meiosis) and uneven, occurring in short chromosomal intervals known as ‘hotspots’. As a result, genes located in crossover-poor regions are more likely to be inherited together, while genes separated by crossover hotspots are more likely to be inherited separately. Distribution of crossover hotspots along chromosomes, therefore, underpins the diversity of life.

The determinants of the hotspots’ chromosomal positions in plants, yeasts and birds remain a long-standing mystery. My lab is using pioneering chromosome engineering technologies to reposition known plant crossover hotspots to new chromosomal environments to test hotspot portability across the genome and understand whether crossover hotspots are defined by local DNA features.

Can de novo crossovers be engineered in defined genomic locations?

Crossovers are initiated by programmed double-strand breaks (DSBs) in the DNA. However, in many eukaryotes, including plants, only approximately 10% of DSBs are repaired as crossovers. An epistatic group of six proteins promotes crossover formation, however, despite the fundamental advances provided by genetics and cytology, it remains unclear how the pro-crossover proteins assemble into higher-order protein complexes and why only a subset of DSBs mature into crossovers. We aim to leverage innovative proteomic tools to understand how the higher order pro-crossover protein complex selects some but not other DSBs to be repaired as crossover and whether crossover positioning can be engineered via synthetic tethering of the pro-crossover protein complex to the DNA.

How can we expedite (legume) crop genetic improvement?

Conventional crop breeding is limited by the intrinsic limitations of crossover recombination that constrain trait reassortment. Legumes are an important source of plant-based protein for human nutrition and an important crop for agricultural sustainability due to symbiotic nitrogen fixation. However, wider use of legumes is limited due to crop yield instability and sub-optimal nutritional qualities (e.g. bitterness and off-flavours in a UK’s legume crop pea). Precision breeding via CRISRP/Cas gene editing offers an alternative to conventional breeding, however, genetic transformation in pea remains a major bottleneck due to its complexity and low efficiency. To overcome this problem, we are developing technologies to deliver CRISPR/Cas9 machinery into peas via plant viruses to edit both agronomic traits and crossover modifiers to accelerate trait reassortment for conventional breeding. Our current model is pea, but the long-term aim is to translate this knowledge to other legumes and non-leguminous crops of UK and global importance.