Balmant gives some insights into the publication in the Q&A below:
Q: In your opinion, what was the most exciting result of this manuscript? Why?
A: "The discovery of a master regulator of the lignin biosynthetic pathway, not yet shown to be involved in regulating the genes involved in the lignin biosynthesis. Its discovery was only possible because we used a system genetics approach. A traditional association study wouldn’t allow us to identify this gene as a regulator of the lignin biosynthesis pathway."
Q: How did the use of a system genetics approach enable you to discover novel information about the control of lignin production in Populus deltoides?
A: The use of system genetics approach was crucial to enable us to discover Myb125 – a master regulator of the lignin biosynthetic pathway. In the field of plant statistical genomics, most of the studies are conducted with relatively small populations. This limits the power to detect variants affecting gene expression. In other words, the use of small sample sizes in expression quantitative trait loci (eQTL) studies hampers the discovery of variants that contribute to gene expression regulation and further identification of potential master regulators of biosynthetic pathways and metabolic networks. In our study, we overcome this challenge by coupling information from co-expression networks and eQTL studies to unravel a key genetics driver of a complex traits. Gene networks can be used to infer the functions of genes based on their close network neighbors. Therefore, by combining gene network with eQTL data one can also find genetic variants responsible for the co-regulation of genes in a given network.
Furthermore, it is widely known multiple testing correction when used in an association study, in which a large number of tests is performed, may lead to a very high rate of false negatives. In other words, multiple testing corrections control false positives at the expense of many more false negatives. Hence, in studies of genomics and statistical genetics one must find a way how to balance false positives and false negatives results. In our study, the use of a system genetics approach allowed us to balance the false positive and false negative results. This, through gene co-expression network analysis, was critical for the identification of Myb125 as a positive regulator of the lignin biosynthetic pathway.
Q: How do you see systems genetics influencing future work both within your lab and in the field of genetics and genomics?
A: In plants and animals, the identification of “master regulators” is critical for the manipulation of complex traits either through genetic engineering or traditional breeding, as they profoundly impact developmental and regulatory pathways. As mentioned before, especially in plant research, the discovery of these “master regulators” by traditional association studies is challenging; and the use of system genetics approach may overcome this challenge.
Q: What are the implications of your results for both the understanding of lignin biosynthesis and the biofuel industry?
A: "Wood is the most abundant biomass on earth, mainly composed of secondary cell walls (SCW). The most abundant components of SCWs and terrestrial biopolymers are cellulose and lignin, accounting for approximately 30% of the organic carbon present in the biosphere. In addition, lignin is also the major contributor to the recalcitrance of biomass, which considerably increases its processing cost and, consequently, biofuel production. Because of the economic importance in pulp and biofuel production, understanding the molecular mechanisms regulating SCW deposition is not only an important topic in plant developmental biology but also fundamental for providing molecular tools to manipulate wood composition for bioenergy use. To date, regulators of the lignin biosynthetic pathway have been described in several species, but the regulation of the components of biosynthetic pathway is not fully characterized and understood. In our study, we identified a new positive regulator of the lignin biosynthetic pathway not yet shown to regulate lignin biosynthesis, which could be further genetically manipulated (through genetic engineering) to generate trees with low content of lignin."