Characterization of Metal-Responsive Transcription Factor (MTF-1) from the Giant Rodent Capybara Reveals Features in Common with Human as Well as with Small Rodents (Mouse, Rat). Short Communication

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 32 aa 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.