Metal pollution has made a significant impact on the earth's ecosystems and tolerance to metals in a wide variety of species has evolved. Metallothioneins, a group of cysteine-rich metal-ion binding proteins, are known to be a key physiological mechanism in regulating protection against metal toxicity. Many rivers across the southwest of England are detrimentally affected by metal pollution, but brown trout (Salmo trutta L.) populations are known to reside within them. In this body of work, two isoforms of metallothionein (MetA and MetB) isolated from trout occupying a polluted and a control river are examined. Using synthetic genetic array (SGA) analyses in the model yeast, Saccharomyces cerevisiae, functional genomics is used to explore the role of metallothionein isoforms in driving metal tolerance. By harnessing this experimental system, S. cerevisiae is used to (i) determine the genetic interaction maps of MetA and MetB isoforms; (ii) identify differences between the genetic interactions in both isoforms and (iii) demonstrate that pre-exposure to metals in metal-tolerant trout influences these interactions. By using a functional genomics approach leveraged from the model yeast Saccharomyces cerevisiae, we demonstrate how such approaches could be used in understanding the ecology and evolution of a non-model species. [ABSTRACT FROM AUTHOR]