Abstract

From mammals to insects, metal-responsive transcription factor 1 (MTF-1) is essential for the activation of metallothionein genes upon heavy metal load. We have previously found that human MTF-1 induces a stronger metal-response than mouse MTF-1. The latter differs from the human one in a number of amino acid positions and is also shorter by 78 aa at its C-terminus. We reasoned that the weaker metal inducibility might be associated with a lesser demand for tight metal homeostasis in a low-weight, short-lived animal, and thus set out to determine the sequence of MTF-1 from the largest living rodent, the Brazilian capybara that can reach 65 kg and also has a considerably longer life span than smaller rodents. An expression clone for capybara MTF-1 was then tested for its activity in both mouse and human cells. Our analysis revealed three unexpected features: (i) Capybara MTF-1 in terms of amino acid sequence is much more closely related to human than to mouse MTF-1, suggesting an accelerated evolution of MTF-1 in the evolutionary branch leading to small rodents; (ii) capybara MTF-1 is even 32aa shorter at its C-terminus than mouse MTF-1 and (iii) in an activity test it is not more active than mouse MTF-1. The latter two findings might indicate that capybara has evolved in an environment with low heavy metal load.