A point accepted mutation — also known as a PAM — is the replacement of a single amino acid in the primary structure of a protein with another single amino acid, which is accepted by the processes of natural selection. This definition does not include all point mutations in the DNA of an organism. In particular, silent mutations are not point accepted mutations, nor are mutations that are lethal or that are rejected by natural selection in other ways. A PAM matrix is a matrix where each column and row represents one of the twenty standard amino acids. In bioinformatics, PAM matrices are sometimes used as substitution matrices to score sequence alignments for proteins. Each entry in a PAM matrix indicates the likelihood of the amino acid of that row being replaced with the amino acid of that column through a series of one or more point accepted mutations during a specified evolutionary interval, rather than these two amino acids being aligned due to chance. Different PAM matrices correspond to different lengths of time in the evolution of the protein sequence. Biological background The genetic instructions of every replicating cell in a living organism are contained within its DNA. Throughout the cell's lifetime, this information is transcribed and replicated by cellular mechanisms to produce proteins or to provide instructions for daughter cells during cell division, and the possibility exists that the DNA may be altered during these processes. This is known as a mutation. At the molecular level, there are regulatory systems that correct most — but not all — of these changes to the DNA before it is replicated. One of the possible mutations that occurs is the replacement of a single nucleotide, known as a point mutation. If a point mutation occurs within an expressed region of a gene, an exon, then this will change the codon specifying a particular amino acid in the protein produced by that gene. Despite the redundancy in the genetic code, there is a possibility that this mutation will then change the amino acid that is produced during translation, and as a consequence the structure of the protein will be changed. The functionality of a protein is highly dependent on its structure. Changing a single amino acid in a protein may reduce its ability to carry out this function, or the mutation may even change the function that the protein carries out. Changes