“Breeding systems and their genetic basis to improve quality and production of animals”

1. “Breeding systems and their genetic basis to improve quality and production of animals” Chris Moran Professor of Animal Genetics and Animal Biotechnology, Centre for Advanced Technologies in Animal Genetics and Reproduction, Faculty of Veterinary Science University of Sydney HSC Agriculture Lectures 2005

2. Elective 2 – Animal Management • discussing the impact or potential impact of genetic engineering and associated technologies on animal production systems. HSC Agriculture Lectures 2005

3. The target • I will focus on one specific target for genetic engineering to improve animal productivity • This target relates specifically to ruminants, such as sheep, cattle and goats • I will then briefly list some other targets for genetic engineering modifications HSC Agriculture Lectures 2005

4. Limiting availability of sulphur amino acids • Proteins are synthesised from a set of 20 different amino acids • Dietary proteins are necessary for animal growth, milk production and fibre production • Essential amino acids are those which must be acquired in the diet. • The two sulphur amino acids, cysteine and methionine, are the major dietary limiters to ruminant growth and productivity • Rumen micro-organisms break down dietary protein, which may have plenty of cysteine and methionine, and re-synthesise their own proteins, deficient in these amino acids HSC Agriculture Lectures 2005

5. How can genetic engineering help? • Engineer the animal • Engineer the plants • Engineer the rumen micro-organisms HSC Agriculture Lectures 2005

6. Modifying the animals • Mammals have long lost the necessary biosynthetic pathway for producing their own cysteine from inorganic sulphur. • Ruminants have abundant H2S in their gut due to digestion of plant proteins by rumen microbes • Can we restore the lost ability to synthesise this amino acid? HSC Agriculture Lectures 2005

7. Cysteine biosynthetic pathway in bacteria HSC Agriculture Lectures 2005

8. A transgene has been constructed including both these bacterial genes in tandem • Controlled by a mammalian metallothionein promoter, which directs expression to the small intestine. • Transgenic mice fed a cysteine deficient diet supplemented only by Na2S had no signs of cysteine deficiency, such as hair loss and loss of body weight • Introduced into sheep but not perfected HSC Agriculture Lectures 2005

9. Modifying plants • Some proteins escape rumenal digestion and make it through to the small intestine • Proteins can be chemically protected to prevent rumen digestion • Alternatively plants can be engineered to produce proteins which escape rumenal digestion and which have a good amino acid balance HSC Agriculture Lectures 2005

10. HSC Agriculture Lectures 2005

11. The SFA8 gene has been transferred to peas and lupins and other legumes • Transgenic proteins have been produced at levels of up to 2% of total seed protein. • A level of 4% of SFA8 would increase sulphur amino acids by 40%, which would have a substantial impact on animal productivity. • It has also been expressed in leaves – more relevant for grazing animals HSC Agriculture Lectures 2005

12. Modifying micro-organisms • To produce an appropriate balance of essential amino acids, including the sulphur amino acids as well as threonine, isoleucine and leucine • Genes encoding natural proteins- SFA8 and casein have been introduced into rumen micro-organisms to attempt to do this • An artificial protein – MB1, enriched in the essential amino acids, methionine, threonine, lysine and leucine, which comprise 57% of the protein, has been expressed at high levels in E. coli HSC Agriculture Lectures 2005

13. Other ways to influence animal productivity and product value • ANIMAL MODIFICATIONS • Growth hormone transgenes – work well in fish • Anti-sense and siRNA protection against pathogens, especially viruses • Chitinase in skin to protect against fly strike • Adding nutraceuticals to milk eg lactoferrin HSC Agriculture Lectures 2005

14. Other ways to influence animal productivity and product value • PLANTS • Improving plant digestibility by reducing lignin content – disrupting the lignin biosynthetic pathway • Edible vaccines – expressing viral and bacterial antigens in plants to vaccinate animals orally – much preliminary work in mice (E coli, Norwalk virus, hepatitis B, mink enteritis virus) • Passive immunisation –producing antibodies in plants – plant antibodies have recognised target molecules HSC Agriculture Lectures 2005

15. Other ways to influence animal productivity and product value • Microbes • Production of animal hormones eg bovine and porcine somatotropin (growth hormone) • Production of numerous vaccines eg Tickgard • Modifying rumen microbes to better digest cellulose • Modifying rumen microbes to detoxify chemicals in diet eg introduction of dehalogenase to Prevotella ruminicolla to detoxify fluoroacetate (1080) from Acacia georginae HSC Agriculture Lectures 2005

16. HSC Agriculture Lectures 2005

17. Conclusions • Genetic engineering of animals, plants and microbes has much to offer animal production system • The greatest impact on animal production has been indirect • There are still substantial social and regulatory restrictions on genetic engineering of animals for improved productivity HSC Agriculture Lectures 2005