Modern and future forestry based on biotechnology

Forest is the most important terrestrial component of the Earth's biosphere, containing nearly 80% of terrestrial biodiversity. However, climate change and population growth are exacerbating deforestation and forest degradation. Reforestation efforts aim to restore ecosystems, but the effectiveness of traditional tree plantations in repairing the ecological function of native forests is controversial. The ideal scenario for forestry in the future is to meet the growing demand for forest products while keeping forest sustainable development. One possible way forward is to greatly improve the productivity and adaptability of forests through molecular breeding to use fewer Short Rotation Intensive Culture (SRIC) plantations to produce sufficient forest products. In the last 2 decades, advances in biotechnologies such as high‐throughput sequencing and genome editing are transforming tree breeding and forestry. Here, we propose possible future directions for modern forestry, including molecular design tree breeding, agroforestry and mixed farming, sustainable and biosphere friendly forestry.


INTRODUCTION
As an essential component of the ecosystem, forests cover nearly one third of the Earth's land mass, providing people with oxygen, clean water, suitable climate and 80% of terrestrial biodiversity. 1 Plantation forests also directly provide us with various forest products and livable urban environment. With the increasing awareness of the essential role of natural forests in soil and water conservation, ecological protection and biodiversity conservation, the modern forestry is gradually shifting from natural forest harvesting to creating a more productive, profitable, biosphere friendly, healthy, and sustainable forestry production system.
Ideally, the development of forestry should be parallel to environmental protection. If plantations are able to offset the demand for all forest products using less land, most natural forests will be protected from deforestation.
In that case, the woodlots with ecological function and productive function could be separated. To meet this demand, the modern forestry is becoming more and more agriculturalised, as the productivity improvement increasingly depends on the breeding innovation, the large-scale application of a few excellent clones/varieties, the intensive water and fertiliser management, the clear-cutting in shorter rotation periods, etc.
Over the past 2 decades, the genomics of non-model forest tree species, which was difficult to study in the past, have made great progress owing to the development of some revolutionary novo biological technologies such as high-throughput sequencing and genome editing. The advancement of these new technologies will inevitably have a profound impact on in the breeding and forestation paradigm of forestry in the future. Here, we propose strategies for the future development prospects of modern forestry, including molecular design tree breeding, agroforestry and mixed farming, healthy and biosphere friendly forestry under the background of the rapid development of biotechnology ( Figure 1).

ACCELERATE FOREST TREE BREEDING
Molecular design for breeding desirable traits has triggered a new wave of innovation in agricultural breeding, 2 especially with the rapid development of genome editing technology in the past decade. 3 Although only a few tree species, including Populus, 4,5 Picea glauca, 6 Cryptomeria japonica 7 and Pinus radiata, 8 can be successfully conduct genome editing at present, this feasibility has opened the door to the possibility of molecular design breeding in other trees. Although the regeneration and genetic transformation are still bottlenecks of tree molecular design breeding, the recent discovery of a number of regenerative regulatory factors in plants, such as BABY-BOOM (BBM), WUSHEL2 (WUS2), WUSCHEL-RELATED HOMEO-BOX 5 (WOX5), GROWTH-REGULATING FACTOR4 (GRF4) and GRF-INTERACTING FACTOR 1 (GIF1), [9][10][11] has made a major step towards establishing genetic transformation protocols independent of plant materials/species or genotypes that could be used in most laboratories (Figure 1).
Beyond the apparent concerns for wood productivity and adaptive traits, greatly shortening the very long breeding cycle may be an important direction for future breakthrough in tree breeding. Unlike annual crops, perennial trees take several years or even decades to gain reproductive capacity, and although each adult tree could periodically provide many more seeds than crops each year, multi-generational selection is more important for breeding programs than seed production, especially for future clonal forestry applications. Some candidate key regulators mediating the vegetative-toreproductive transition have been identified in both angiosperms trees 12,13 and conifers, 14,15 and the appropriate regulation of these genes provides a potential biofortification tool to accelerate the reproductive development of important forest trees ( Figure 1). By manipulating a few reproductive transition regulators to obtain early flowering and dwarf parent trees with shortened reproductive cycle to 1-2 years, similar to shrubs or crops, will bring revolutionary convenience to the implementation of breeding operation and land use. Based on the current biotechnology such as dual reproductive cell-specific promoter-mediated split-cre/ loxp system, 16 it is easy to remove flowering regulatory factors in progeny trees and restore their normal growth.
Besides the long period of vegetative growth, the long-time of progeny phenotyping of fully developed  offspring trees is also a limitation of traditional genetic breeding. The ideal solution in the future may be the early whole genome-assisted selection based on accurate phenotyping of seedlings or saplings growing under strictly controlled growth conditions (Figure 1), and combining the correlation between early and late growth phenotypic traits. 17,18 Shortening the breeding and progeny testing cycle not only has direct economic and time benefits, but also makes it easier to response in a timely manner to adapt the breeding programme to meet the changes in market demand. For example, with the innovation of wood processing and utilisation, 19,20 forestry breeders need to pay more attention to the population productivity of a woodlot instead of the maximum growth potential of an individual tree. Therefore, tree breeding needs to shift from emphasising only tree height and stem growth rate in the past to the ideotype of tree architecture.
Genetic advances achieved through short-cycle and small-scale fine breeding can be rapidly amplified through the clonal forestry. Both theoretical studies and experimental data from progeny and clonal trials indicate that the clonal forestry could effectively double the genetic gain that achievable through family forestry within the same generation. 21 Although there are some concerns about the risk of clonal forestry, both in terms of biodiversity and serious diseases or pests, these issues are actually unnecessary in modern forestry with short-rotation period 21 especially when the ecological functions and productive functions are separated. Currently, the clonal forestry of some fast-growing deciduous trees, such as eucalyptus, poplar, and willow, has achieved great success. [22][23][24] These commercial plantations are usually planted on relatively flat and fertile land, and have a short rotation period by applying improved speciality fertilisers. These clonal trees of the same genotype have uniform architecture and growth rate, so they can be harvested by machine and provide wood with very stable chemical composition and physical properties, which further facilitates the subsequent processing and utilisation, and ensures the stability of product quality ( Figure 1). These characteristics make forestry tend to be similar to agriculture, therefore, these trees are called 'woody crops'. 25

AGROFORESTRY AND MIXED FARMING SYSTEM
In the past century, the increase in world population was three times greater than during the entire previous history of humanity. Productive land has always been chosen to grow crops to provide enough food for expanding populations. However, this intensification of agriculture has been accomplished at great expense to the environment, causing water scarcity, soil degradation, loss of biodiversity, high levels of greenhouse gas emissions, significant reductions in forest cover and ecosystem destruction. 26 The intensive agriculture concept of 'getting more for more' that is, producing as much biomass as possible with vast monocultures dependent on irrigation systems, fertilisers, and pesticides is no longer acceptable. Instead, the sustainable intensification agriculture of 'getting more from less' is proposed.
Agroforestry is a traditional but a sustainable land management system that can optimise the benefits of the biological interactions created when trees and/or shrubs are deliberately combined with crops and/or livestock. 27 An example of agroforestry practices is the combination of trees planted in rows with crops cultivated in the alleyways between the tree rows ( Figure 1). A growing body of research suggests that agroforestry practices can provide a wide range of benefits in response to the deepening sustainability and climate crises. [28][29][30][31] Well-designed agroforestry systems will provide more favourable microclimates with increased biodiversity and reduced wind velocity, improved pest and weed suppression, reduced soil erosion, increased water infiltration, improved production potential through increased crop yields, and diversification of production by generating products from the intercropped trees. 32 Common to all agroforestry practices is the need to provide the right tree for the right purpose on a given site. Trees that selected for agroforestry practices must be able to tolerate changing environmental stresses and resist ongoing threats from changing insects and pathogen populations. There are many tree species that are useful for agroforestry, yet the lack of multigenerational and genetic pedigrees of agroforestry species has limited the biological research on these trees. The development of biotechnologies such as somatic embryogenesis, genetic engineering, and marker-assisted selection has accelerated the efficiency of tree breeding. 33,34 However, most research has tended to focus on a few model species such as poplar, eucalyptus and pine. In the future, information and technologies that are developed for model species can be applied to agroforestry species. In addition, the cross integration of various disciplines such as ecology, agronomy, biology etc. is required for agroforestry development. Specialised research in all aspects of forest biology is required before the unique features and ecological interactions of woody plants are fully understood. Such information is essential for efficient selection and provision of the right genotypes for the specific sites and purposes in agroforestry systems. 35

FORESTRY BENEFITS FOR HUMAN HEALTH
The forest is a complex green infrastructure system that delivers multiple functions and services to the environment and human beings. In addition to the wellunderstood environmental and economic values, trees provide a range of human health benefits that are often under-recognised. 36 While a broader understanding of the relationship between forests and health is needed, the benefits of living with trees cannot be overstated. Modern forestry will be indispensable to meeting global health challenges in the future. Cutting-edge biotechnologies and modern design of forestry will enable forests to produce more healthy food and useful MODERN AGRICULTURE -29 medicines and make the environment more beautiful. Through their perennial and sustainable growth and abundant secondary metabolites, forests provide low-cost, nutritious food to much of the developing world and to rural communities, making a significant contribution to combating malnutrition and improving global food security. 37 The phenotypes associated with forest foods deserve more attention for genetic improvement during domestication and artificial breeding of trees in modern forestry. With the molecular dissection of these phenotypes, genome editing-based breeding by molecular design in trees will be explored to provide more and higher quality forest foods. Agroforestry and mixed farming systems are ideal choices for constructing the cost-saving and environmentally friendly mode of forest food production.
Humans have relied on medicinal trees for thousands of years to derive a wide range of life-saving medicines across cultures. 38 The abundant metabolites and derivatives produced by trees enable forests to provide an inexhaustible natural source of bioactive compounds with relevant therapeutic properties and clinically useful drugs. 39,40 For example, paclitaxel, a widely used anticancer drug, for example, was first isolated from stem bark extracts of Taxus trees. 41 Modern and multifaceted approaches involving phytochemical, pharmaceutical, biological, and molecular techniques will facilitate drug discovery from trees in the future. The exploration of more bioactive compounds of trees for medicinal purposes sheds light on the high value of modern forestry. Whole genome sequencing provides an efficient and cost-effective tool in trees to elucidate the biosynthetic and regulatory pathways of bioactive compounds. Metabolic engineering and synthetic biology approaches will be widely used to modify or reconstruct the biosynthetic pathways of forestderived medicinal compounds in tree cells or engineered organisms. In addition to the ecological value of forests in reducing global greenhouse gases, the critical role of urban trees in air purification directly links forestry to human health and daily life. Air pollutants or toxins in the form of PM2.5, PM10, carbon monoxide, nitrogen dioxide, sulphur dioxide, benzopyrene and ozone are strongly associated with human health and significantly increase the risk of many diseases. Forests can significantly reduce these adverse health effects by absorbing or detoxifying these substances. 42 Molecular understanding of pollutant detoxification will enable biotechnology-based approaches to develop trees with enhanced air purification capabilities in future forestry.
Modern forestry should meets the demand for a beautiful and friendly environment in people's lives, which also requires biotechnologies in the future. In addition to greening, colouring is another goal of reforestation and landscaping in cities and surrounding areas. Phenotypes with evergreen or colourful leaves have already been the main targets of tree breeding. Recently, bioengineered tobacco plants with genetically encoded autoluminescence have been successfully generated. 43 It will be realisable to construct autoluminescent trees that can be recognised by the naked eye. Besides, some current plantation trees also cause health problems, for example, the catkins of poplar and willow that for seed dispersal make people suffering from allergies. Thanks to the gene identification of sexdetermining systems in trees, the catkin problem is expected to be solved by genome editing-based gene knockout in poplar. 44 Increasing green cover and proper forest structure, which depend on more diversified tree species developed through genetic breeding and modern biotechnologies, will make modern forestry an essential component of healthy environments (Figure 1).

BIOSPHERE FRIENDLY FORESTRY
As noted above, forests play a critical role in providing a range of ecosystem services and invaluable products. However, the impacts of rapid climate change and the pressures from human activities are pose considerable risks and challenges to forest ecosystems. 45,46 The loss and fragmentation of forests, particularly exacerbated by anthropogenic threats, has caused serious negative consequences for forest biodiversity. It further jeopardises forest ecosystem functions and services, including the reduced resistance to invading pathogens, pests and climate extremes. [47][48][49] In response to these challenges, the use of genetic engineering, particularly of the CRISPR-based gene editing, has emerged as a prominent approach to either help mitigate the effects of climate change on forest trees or help organisms to adapt to anticipated future climate change. 50 The application of gene editing to traits such as abiotic stress tolerance, disease resistance, carbon fixation, wood quality and yield enhancement to rescue forest trees from increasingly pressing climate challenges is one of the most promising solutions for improving forest resistance and sustainability to climate hazards.
To compensate for the increasing anthropogenic CO 2 emissions and to meet growing population pressure for the need of forest services, ambitious large-scale forest restorations are underway worldwide, mostly aimed at increasing carbon sequestration, enhancing forest carbon stocks and also meeting the demand for products and livelihoods provided by forest ecosystem services. 51 The advancement of sequencing and genomic technologies are believed to offer the potential to achieve the triple win of climate, society and biodiversity in future reforestation programs. 47,52 Existing and emerging genomic tools facilitate the consideration and assessment of biodiversity at multiple levels, including species, populations and genetics. The selected species are key factors influencing the functional diversity and productivity during tree planting and restoration. 53 Metaomics approaches can help to characterise and quantify the diverse and functional taxonomic groups of environmental microbiota, which can be used to evaluate the selection of species that can maximise biodiversity and resist to extreme climate events. 54 Apart from species level, the parental population from which seeds or seedlings were derived is also a key determinant of longterm success of forest breeding and restoration. 55 After integrating population genomics with predictive climate modelling approaches, the parental populations with 30 -MODERN AGRICULTURE genetic compositions that match future climatic conditions at local sites should be selected to serve as seed supply sources to ensure the survival, disease-prone and resilience to rapid future environmental changes of planted forests. 56,57 Finally, genomic tools facilitate the estimation and assessment of genetic diversity and variability of planted trees ahead any future reforestation projects. Plant materials with low standing genetic diversity are supposed to have reduced responses to natural selection, further increasing the risk of population decline under rapid climate change. 58 Therefore, the use of seed sources with appropriate levels of genetic variability is vital to maximise population functionality and resilience, as well as to increase levels of both aboveground and belowground biodiversity.
Taken together, although large-scale reforestation programs are currently underway and will be urgently needed in the future, the protection of existing natural forests, especially old-growth forests, should always be set to a higher priority. The complex structure and dynamics of natural forests give great value for natural biodiversity conservation and carbon storage, while the reforestation cannot compensate or replace the loss of natural forests in the short term. 59 Moreover, we emphasise the involvement of local communities and interdisciplinary collaboration to jointly address the urgent solutions for forest protection and reforestation to further mitigate the climate change and other global challenges, such as carbon cycle-climate feedbacks, disturbance from wildfires, soil resource protection and humankind services. 60,61

CONCLUSIONS AND PERSPECTIVES
Undoubtedly, the rapid developments in biotechnology have provided unprecedented opportunities for the breeding of customised ideal forest tree varieties. In particular, the high-fidelity long read sequencing technology makes it theoretically possible to assemble highquality genomes of all tree species, and the gene editing technology has made the creation of desirable genetically modified species easier and more accessible. However, it must be acknowledged that in the new form of climate change and complex forest management environment, modern forestry faces a great challenge and a couple of major issues need to be considered and solved in the future forestry. These outstanding issues include, but are not limited to, how to overcome the transformation recalcitrance for most tree species; how to use genetic engineering techniques properly to breed excellent varieties with fine performance (e.g., carbon fixation, adaptability, productivity, wood quality, management efficiency); how to breed desirable tree varieties adapted to geographical and climatic factors in different afforestation ecological areas; how to rescue endangered tree species and restore fragile forests sensitive to climate change; how to combine clonal forest with traditional seed orchards and rapid cultivation and large-scale propagation of improved tree varieties, etc.
It is important to emphasise that the perspective of this paper is oriented to the ideal forestry in the future. In practice, any new technology cannot be separated from the support of traditional technology. The modern biotechnology is not a shortcut for tree improvement that does not require traditional genetic breeding. It is expected that traditional tree breeding will remain the most effective way to obtain new forest varieties for a long time to come. Modern technologies will accelerate the shift of forest tree breeding from traditional empirical techniques to scientific techniques, but there is still a long way to go. It requires the participation and exploration of all researchers engaged in forestry.