GroundCover™ Issue: 138 January - February 2019 | Author: Dr Gio Braidotti
It is one thing to sequence a genome, another to understand what it means. Now, new bioinformatics tools are making it possible to properly exploit the bread wheat genome sequence in breeding programs
Knowledge of the bread wheat genome has come of age after years of researchers grappling with its size and genetic complexity.
Now, the genome has been sequenced, its key genetic structures decoded, and differences between cultivars identified in ways that support accelerated rates of genetic improvement.
The milestone was made possible by two concurrent advances. The first involved the technically challenging grunt work of sequencing the entire genome in small fragments and then assembling that sequence in the correct order. The second involved analytical methods to make sense of the resulting enormous dataset.
Crucial to cracking the analysis challenge is Dr Ute Baumann, who heads the bioinformatics program at the Australian Research Council (ARC) Industrial Transformation Research Hub for Wheat in a Hot and Dry Climate, located at the Waite campus of the University of Adelaide.
GRDC investment made it possible for Dr Baumann to develop a web-accessible bioinformatics platform called Diversity Among Wheat geNomes (DAWN). This platform provides unprecedented – and once unimaginable – insights into the structure, genetic function, genealogy and biodiversity of the bread wheat genome.
Associate Professor Delphine Fleury, who heads the ARC wheat hub, says the bioinformatics breakthrough was essential for the grains industry to benefit from global efforts to fully sequence the wheat genome.
“If we can’t read the sequence information, we can’t use it,” Associate Professor Fleury says. “The genome is big – 39.5 times bigger than the rice genome and 5.6 times larger than the human genome. That poses computational challenges to handle, search and sort through that much sequence data. That’s the problem that Dr Baumann solved. She gave us access to the genome.”
The key to learning to ‘read’ the genome involved comparing the sequence of 16 different bread wheat cultivars in a process that provided the contrast to understand the functional structure of the genome, both at a macro and micro scale.
Making sense of genetic gibberish
As the University of Adelaide’s representative to the International Wheat Genome Sequencing Consortium (IWGSC), Dr Baumann was aware early on that the gargantuan size of the wheat genome would complicate its use as a research tool.
In 2017, however, she caught sight of a way to solve the analytical challenge.
Dr Baumann explains that Bioplatforms Australia (BPA) used advanced sequencing technology to process the genomes of 16 different wheat cultivars. Importantly, the set included 11 Australian varieties, including Baxter (which expresses novel rust resistance), Drysdale (which has enhanced water use efficiency), Gladius and Yitpi.
“Comparative genomics produces an extraordinary amount of information because it can create a picture of the function associated with different areas of the genome,” Dr Baumann says.
There was one major obstacle, however. To sequence a genome, the continuous DNA strand within every chromosome must first be fragmented into tiny pieces before they can be sequenced. To achieve this, BPA used a technique called ‘shotgun sequencing’ that creates dire difficulties assembling the fragmented sequence into the right order.
To solve what amounts to the world’s greatest jigsaw puzzle, Dr Baumann made use of data produced by the IWGSC that provided clues to the right way to assemble the fragmented DNA sequence. From data that initially meant little, emerged an entirely unprecedented view of bread wheat genetics.
“For the first time, we have achieved insights about the wheat genome that don’t just describe, but explain cultivar performance,” Dr Baumann says. “We can just about see how cultivars were bred just from the structure of their genome. We can even start to predict optimal genomic configurations needed to achieve higher-performing, new varieties.”
This amounts to gateway technology to establish predictive breeding capability for the wheat industry, as has already occurred for maize hybrids in the US.
“That is where we see the future going,” Dr Baumann says. “Essential to that goal is the ability to understand the genome structure that underlies genetic diversity, including the major agronomically important traits – flowering time, height, quality and yield genes. Only then can we try to design and construct a variety based on optimal gene variants and gene combinations while also designing the best breeding strategy to achieve that ideal cultivar.”
The inclusion of Australian cultivars within DAWN further means Australia is on the frontline of exploiting this astonishing new capability, with wheat-breeding companies, such as Limagrain, already expressing interest in tapping the analytical power of Dr Baumann’s bioinformatics tools.
Brought into focus by DAWN are both large and small-scale details.
Visible on a chromosome-wide basis is the intrusion of large segments of DNA from species related to wheat (called an alien introgression), including segments that have brought in important new traits, such as the rust-resistance gene Sr36. Dr Baumann can now account for chromosomal regions that will happily exchange and recombine DNA during reproduction and those that will not, causing genes contained within the region to always be inherited together.
“We can then also zoom into specific regions where we can find sequence differences of a single letter in the genetic code,” Dr Baumann says. “This kind of sequence diversity can account for trait variation between cultivars. It also allows researchers and breeders to develop diagnostic markers for important traits.”
An example of exploiting this level of resolution is the development of markers diagnostic for amylose content in grain. Another is the identification of two genes for yield – including one that is associated with heat tolerance – both located on the Australian-sequenced chromosome 7A.
“Bioinformatics is what grants researchers access to the wheat genome and it is sharpening our understanding of how best to develop new varieties,” Associate Professor Fleury says. “We can now see those regions that pose problems for breeding and can hold up genetic gain. So knowledge of genome structure matters to the grain industry, especially for a complex genome like wheat.
Dr Ute Baumann
Associate Professor Delphine Fleury
DAWN bioinformatics are publicly accessible here.