Antifreeze glycoprotein (AFGP) that circulates in the blood of polar-adapted notothenoid and cod fishes enables them to avoid freezing. AFGP is maintained at high circulatory levels owing to its large gene families in that each gene encodes a large polyprotein precursor. This precursor is post-translationally cleaved into multiple AFGP molecules. Highly conserved three residue spacers link each AFGP molecule in the polyprotein. The AFGP comes in several isoforms of different sizes. The AFGP from Antarctic notothenoid giant toothfish Dissostichus mawsoni is thought to have evolve from the pancreatic enzyme trypsinogen however the AFGP from the Arctic cod Boreogadus saida has been affirmed not to have evolve from trypsinogen.
Recently, in a brief paper (Cheng, et al. Nature 401:443) a chimaeric gene resembling that of AFGP and trypsinogen was discovered. This gene resembled an intermediate of the evolutionary progress between trypsinogen and AFGP. The chimaera has significant sequence homology of AFGP’s polyprotein nucleotide sequence, that is the conserved nine-nucleotide tripeptide repeat sequence (Thr-Ala/Pro-Ala). It appears this repeat sequence is a multiple duplication of a short region of sequence in the second exon of trypsinogen. This repetitive area could not be just a mere coincidence in homology. A GT minisatellite DNA sequence appears inherited as well from the end of the first intron in all the homologous genes. It is thought that this GT repeat could have facilitated the duplication of the ancestral Thr-Ala-Ala repeat coding element through accidental replication slippage. The chimaera, which possesses the sequences of the AFGP polyprotein encoded within its second exon, also has the intron-exon arrangement and boundaries identical to that of trypsinogen. It is believed that the stop codon of exon six in the chimaera and the trypsinogen is the parental stop codon of present day AFGP.
Earlier papers by Chen, et al (PNAS 94:3811) hypothesised that, given the common sequence elements between the trypsinogen and AFGP genes and the Thr-Ala-Ala coding element in the second exon of the trypsinogen gene, the primitive AFGP arose due to trypsinogen duplication, rearrangement or segment-recycling, and de novo amplification. The first exon and intron of trypsinogen, plus several nucleotides of the second exon and the stop codon area, were kept whilst the rest of the gene was deleted to form a very basic AFGP. The duplication of the tripeptide sequence produced a hybrid, that could possibly be the trypsinogen-like protease gene, which further along led to the evolution of today AFGP. The authors note that the second Ala of the tripeptide in present day AFGP can function well still with a Pro in place. A proline substitution requires just one base change from the Ala codon gct to cct, and statistically speaking, this strengthens the idea that the triplet repeat in AFGP is derived from trypsinogen and not from some random nucleotide segment insertion.
The Arctic cod also possess AFGP that is functionally identical and even its sequence is appears alike at first glance. This includes that same tripeptide repeat that makes up the backbone for an effective AFGP. However in another article, Chen, et al (PNAS 94:3817) has staked that the two AFGP have evolved independently and the attributing similarities all owe it to convergent evolution. He explains that the Arctic cod AFGP genes share no sequence identity, as a significant proportion of areas of the gene do not relate at all to trypsinogen. The signal peptide of the Arctic cod’s AFGP gene is significantly longer and entirely different to the notethenoid’s. Besides plain sequence differences, the intron-exon boundaries are different between these two polar fishes. Intron-exon boundaries generally remain identical in homologous genes, even in highly divergent organisms.
The natural selection for a regular tripeptide sequence, whose folding and thermokinetic properties lessen the impact of freezing on living tissue, has allowed an obvious advantage for the survival of more than 95% of the Earth’s polar ocean biomass. By studying the intermediates of these proteins, we can appreciate the diversity that has been generated as species adapt to an everchanging world. And for us human beings, we may engineer such proteins for potentially unlimited uses, such as the in vivo adaptation to extreme cold without expensive shelter or materials – new innovations await.
0 comments:
Post a Comment