“…Proteins from bacteria and Archaea, for example, often have served to elucidate broad patterns in protein adaptation across wide temperature ranges, and have allowed researchers to define general criteria for structural adaptation to temperature (D'Amico et al, 2003;Siddiqui and Cavicchioli, 2006;Feller, 2008Feller, , 2010Gu and Hilser, 2009). In contrast, studies of enzyme orthologs from closely related species of ectothermic metazoans, such as phosphoglucose isomerase in butterflies (Watt et al, 2003), pyruvate kinase in fish (Low and Somero, 1976) and isocitrate dehydrogenase in mussels (Lockwood and Somero, 2012), have the potential to reveal the minimum amount of environmental temperature change necessary to induce modifications in enzyme function and structure, and what types and magnitudes of amino acid substitutions are sufficient to allow adaptation to a new thermal environment. Of these latter types of studies focusing on orthologs from closely related species, among the most fruitful have been a series of studies using A 4 -lactate dehydrogenase (A 4 -LDH) and cytosolic malate dehydrogenase (cMDH).…”