Protein evolution Flashcards
Define protein evolution
Protein evolution involves the generation of variants that differ in sequence, structure, function. expression level or lifetime. Natural selection then acts to enhance the frequency of alleles with favorable properties.
What are the 2 major sources of variants in protein evolution
> Mutations- these may be substitutions, insertions, deletions in the genome. Some substitutions do not change the amino acid, some change it conservatively(eg. leucine to isoleucine) and some produce amino acid substitutions that more severely change the physiochemical character of the amino acid(eg. glycine to arginine). For insertions and deletions, the protein is more likely to survive an indel of a multiple of 3 bases. Anything else will change the reading frame. In many cases, mutations conserve the general features of a proteins folding pattern without retaining the exact structure. In evolution with retention of function, typically the active site is the best preserved region of the structure.
Proteins can ‘mix and match’ domains. This is a relatively safe way to generate diversity, for recombining domains is likely to produce a protein that forms a native structure. The domains may retain their function in the new structure, but not always.
How can proteins evolve without depriving the cell of the essential function
> One possibility is gene duplication- with the formation of 2 copies, the one can retain the function while the other is free to explore other possibilities. Globins are an example of gene duplication and divergence.
A second possibility is for a single protein to show multiple functions. Then depending on the cells requirements, evolution might optimize the protein for one or another function or retain both. Prokaryotes that need certain functions acquire them by importing plasmids that contain proteins capable of the desired function. This is seen in the spread of anti-biotic resistance in bacteria.
Discuss the evolution of human globins
The human genome encodes several proteins that are related to haemoglobin. The two chains that form the haemoglobin tetramer appear in the alpha and beta clusters on chromosome 16 and 11. Different haemoglobin genes from these clusters are expressed at different developmental stages.
Differences in gene sequences, the corresponding amino acid sequences and the 3D structure reflect gene duplication and evolutionary divergence. The globins within the alpha or beta clusters are more closely related to one another than the members of the alpha cluster is related to the beta cluster. Other globins in the human genome- myoglobin, neuroglobin and cytoglobin- are more distant relatives. Corresponding globins in related species have also diverged, eg. humans and horses. In general divergence at the molecular level runs parallel to divergence that is determined by taxonomic methods.
The power of comparative genomics and proteomics within and among species is immense.
What is the basic tool used for investigating sequence divergence
The basic tool for investigating sequence divergence is the multiple sequence alignment. The amino acids are colour-coded by physiochemical type. Therefore a mutation that leaves the colour unchanged is most likely conservative- making minor changes in structure and function. In (a) the upper case letters indicate that all residues are conserved in all sequences and the lower case letters indicate that all residues in all sequences, except for the sperm whale myoglobin, are conserved. In (b) the multiple sequence alignments of globins from eukaryotes and prokaryotes, they have much fewer conserved residues in their sequences- the uppercase letters are indicate that all residues conserved in all 8 sequences and the lower case residues indicate that all residues, except for the bacterial globin, are conserved in the sequences. The alignment gaps indicate that these are distantly related sequences.
What is the basic tool for investigating structure divergence
Superposition.
