1. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 1 Modeling carotenoid dynamics in salmon BMSW, Bangalore 2008 Hannah Rajasingh Centre for Integrative Genetics (CIGENE) Norwegian University of Life Sciences Ås, Norway

2. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 2 Overview  Background to the pigmentation trait  Research summary –Model setup –Experimental validation and sensitivity analysis –Model extensions  Conclusion

3. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 3 Salmonid pigmentation??  Well-known feature of certain salmonid fish  Affected by both genetic and environmental factors –Genetic factors: intra- and inter-species variation, heritable trait –Environmental factors: diet, temperature etc.  Vital quality trait in aquaculture and thus of economic importance

4. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 4 Carotenoids  Naturally synthesized pigments present throughout the animal kingdom  Function as colouring agents, provitamin A compounds and antioxidants  Xanthophyll astaxanthin is the major carotenoid in aquatic species  High antioxidant activity

5. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 5 Salmonids  Salmonidae contain around 10 genera with well-known members being anadromous  Intricate life-history pattern with many variations  Carotenoid metabolism in pigmented salmonids closely linked with life-cycle changes

6. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 6 Muscle as carotenoid sink Muscle as carotenoid source

7. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 7 Sockeye (Oncorhynchus nerka) Arctic char (Salvelinus alpinus)

8. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 8  Problem: Clearer understanding of metabolic processes governing carotenoid muscle deposition required  Premises: –Carotenoid uptake and transport in the system based on fatty acids –Major features of the carotenoid pathway in salmonids are similar to that in mammals

9. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 9

10. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 10 Mathematical model Flow and uptake of pigment through the system modeled as a function of feed input Pigment concentration in blood, liver and muscle represented by 8 ODEs

11. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 11 Parameters?  Rates of processes unknown  Constraints: –Optimal astaxanthin dietary content –Only 50% enters blood stream –Mean muscle concentration –Muscle uptake saturable with negligible degradation –Strong link with fatty acid transport

12. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 12 Short term feeding Aas et al. 1999

13. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 13 Long term feeding March and MacMilan 1996

14. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 14 Sensitivity analysis: QSS Identify the processes/rates affecting muscle deposition to the greatest extent

15. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 15 Sensitivity analysis: time-series

16. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 16 Pigment redistribution during maturation Claim: Not controlled by a specific regulatory system

17. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 17 Extension: Sites of genetic variations The model is extended to generate population of individuals by adding variances to the specific growth rates.

18. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 18 Extension: mGP representations  The dynamic model is combined with genome models to create mathematical genotype-phenotype representations  Genotypic and phenotypic variations linked within a single framework  Used to determine genetic model required to account for empirical salmon genetic data Genotype of a traitPhenotype of a trait

19. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 19 Conclusion  Early-phase, heuristic model is capable of incorporating available knowledge into a concerted whole  Muscle uptake process seems to have the highest influence on levels of pigment deposition –> potential site of genetic variation  Release of carotenoids from flesh of maturing salmonids does not require a specific control system regulating it

20. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 20 Acknowledgements  Stig W. Omholt  Leiv Øyehaug  Dag Inge Våge  Arne Gjuvsland  Lars Gidskehaug

21. www.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES CIGENE 21 Paper III: Sources of genetic variation  Observed genetic variation not attributable to growth/intestinal uptake is predicted to be due to uptake processes in blood-muscle compartment  Mixed model estimated variances in filet colour (53%) and weight (30%) due to additive genetic effects  Path analysis split pigment variation into contributions from genetic, weight and other factors