Gene expression, amino acid conservation, and hydrophobicity are the main factors shaping codon preferences in Mycobacterium tuberculosis and Mycobacterium leprae

Mycobacterium tuberculosis and Mycobacterium leprae are the ethiological ag ents of tuberculosis and leprosy, respectively. After performing extensive comparisons between genes from these two GC-rich bacterial species, we were able to construct a set of 275 homologous genes. Since these two bacterial species also have a very low growth rate, translational selection could no t be so determinant in their codon preferences as it is in other fast-growi ng bacteria. Indeed, principal-components analysis of codon usage from this set of homologous genes revealed that the codon choices in M. tuberculosis and M. leprae are correlated not only with compositional constraints and t ranslational selection, but also with the degree of amino acid conservation and the hydrophobicity of the encoded proteins. Finally, significant corre lations were found between GC(3) and synonymous distances as well as betwee n synonymous and nonsynonymous distances.