The origin of new genes

Hi Faith,An article recently published in Genomics gives evidence of the mutational origin of new alleles coding for completely novel proteins in human beings. The article is Frequent appearance of novel protein-coding sequences by frameshift translation by Okamura et al.The authors concern themselves with two types of mutation: first, gene duplication (in which a gene coded once in parental DNA is copied incorrectly such that it appears twice or more in offspring DNA); second, frame-shift mutation. I'm sure you know what a frame-shift mutation is, Faith, but I'll explain it for the benefit of others.The nucleotides which make up the sequence for a gene are converted into a protein by the ribosomes, which "read" nucleotides three at a time. Each consecutive triplet of nucleotides corresponds to a single amino acid in the protein. So, a string of 300 nucleotides would result in a protein consisting of 100 amino acids. For example, below is a random string of fifteen nucleotides followed by a string of five amino acids. Like nucleotides which are represented by A,C,G and T, amino acids are also represented by single letter codes:

nucleotides: ATACGATTCTTACTT
protein:      A  R  F  L  L

A frame-shift mutation involves the deletion or insertion of nucleotides such that the triplets are thrown out of sync with the "correct" protein. For example, if the first nucleotide of the sequence above were to be deleted by a mutation, the translated protein would be completely different because instead of "ATA" being the first triplet, "CGA" being the second, etc, the first triplet would be "TAC", the second would be "GAT", etc. See below:

nucleotides: TACGATTCTTACTT
protein:      Y  D  S  Y  X

It's easy to imagine that if duplication of a gene is followed by a frame-shift mutation in one of the copies, that copy would end up producing a completely different protein to that produced by the original version of the gene. According to you, these novel proteins would be deleterious and removed from the genome by selection.The authors of the paper decided to identify the existence of functional proteins arising from duplication and frame-shift mutation in human beings. They searched the databases for known protein-coding nucleotide sequences. For each sequence they generated five possible frame-shifted versions (1: deleting the first nucleotide; 2: deleting the first two nucleotides; 3: reading the sequence backwards; 4: deleting the first nucleotide and reading the sequence backwards; 5: deleting the first two nucleotides and reading the sequence backwards). They then worked out what amino acids these "mutated" sequences would code for in the human body and searched for the existence of such proteins in the DNA databases.They found 470 proteins that appear to have arise by duplication and frame-shift from preexisting genes in the human genome. These proteins are functional in the human body, in that they create proteins that actually do useful stuff inside the cell. But the proteins are completely different to the original version of the gene in terms of their amino acid sequences so they are truly "novel" proteins.The authors generated their simulated mutated sequences from a database of 23000 curated proteins. This means that around 2% of all functional human proteins arose from duplication and frame-shift. That's just from one single type of mutation!If you are unwilling to accept that mutation can generate novel and functional proteins, then you need to explain these results. It seems to me that either spontaneous random mutations do indeed account for the origin of new genes; or, God uses mutations to create new genes. Either way, mutations DO create new, functional genes.I think it is important to point out that the authors of the paper considered the possibility that 470 matches might have occurred simply by chance. They tested this possibility by generating 23000 completely random nucleotide sequences and repeating the experiment. They found zero matches. I would be interested to know how you would explain these results if you persist in believing that mutation does not contribute to the formation of new functional genes.MickEdited by mick, : Added final paragraph and challengeEdited by mick, : edited thread title