Method for optimizing a nucleotide sequence to maximize the expression of a protein in a given organism based on the amino acid sequence of the protein, comprising the following steps performed on a computer: - generating a first test sequence of n codons which correspond to n consecutive amino acids in the protein sequence, where n is a natural number and is less than or equal to N, the number of amino acids of the protein sequence; - specifying m optimization positions in the test sequence which correspond to the position of m codons, in which positions the occupation by a codon, with respect to the test sequence, is to be optimized, where m <= n and m < N; - generating one or more further test sequences from the first test sequence by replacing, in one or more of the m optimization positions, a codon from the first test sequence with another codon which expresses the same amino acid; - rating each of the test sequences with a quality function and determining the optimal test sequence in terms of the quality function; - specifying p codons from the optimal test sequence which are located in one of the m optimization positions as result codons which form the codons of the optimized nucleotide sequence in the positions corresponding to the position of said p codons in the test sequence, where p is a natural number, p <= m, and p is equal to one in one or more iteration steps; - iterating the preceding steps, wherein, in each iteration step, the test sequence contains the corresponding result codon in the positions which correspond to positions of specified result codons in the optimized nucleotide sequence, and the optimization positions are different to positions of result codons. - generating a first test sequence of n codons which correspond to n consecutive amino acids in the protein sequence, where n is a natural number and is less than or equal to N, the number of amino acids of the protein sequence; - specifying m optimization positions in the test sequence which correspond to the position of m codons, in which positions the occupation by a codon, with respect to the test sequence, is to be optimized, where m <= n and m < N; - generating one or more further test sequences from the first test sequence by replacing, in one or more of the m optimization positions, a codon from the first test sequence with another codon which expresses the same amino acid; - rating each of the test sequences with a quality function and determining the optimal test sequence in terms of the quality function; - specifying p codons from the optimal test sequence which are located in one of the m optimization positions as result codons which form the codons of the optimized nucleotide sequence in the positions corresponding to the position of said p codons in the test sequence, where p is a natural number, p <= m, and p is equal to one in one or more iteration steps; - iterating the preceding steps, wherein, in each iteration step, the test sequence contains the corresponding result codon in the positions which correspond to positions of specified result codons in the optimized nucleotide sequence, and the optimization positions are different to positions of result codons. <EOS>