Structural Biochemistry/Bioinformatics/Structural Alignments
Cases where sequence alignments result in less than 25% of identical amino acids usually rule out homology. However, even if the sequences do not demonstrate homology, comparisons of their structures may. A protein’s three-dimensional structure is more related to its function than is its primary sequence. As a result, the tertiary structure is generally more conserved than the sequence. Though proteins in a family group may differ in amino acid sequence, they are characterized by similar structure. An example of this can be seen in the proteins hemoglobin and myoglobin. Though the two proteins differ in sequence, there are both characterized by a similar heme group that allows for the binding and transport of oxygen.
It may also be the case that proteins have structural similarities, but play different biochemical roles and have different amino acid sequences. This is indicative of a common ancestor that evolved into different pathways through what is termed divergent evolution. The proteins are then considered paralogs, which often have different functions within one species. An example of this can be seen in actin and Hsp-70. Though both resemble each other in structure, actin plays a role in muscle contraction and cell motility while Hsp-70 plays a role in preventing stress and heat shock. Another easier example is between our hands and the legs of frogs. Same ancestor and same origin, but came to divert and have different function.
Evaluating Sequence Alignments
The method of sequence alignment can be used to detect the similarity of homology. Two sequences of proteins can be compared by sliding one sequence past the other and record the number of matched residues.
Upon analysis of similar structures, the sequence alignments can be re-evaluated for a better fit. Gaps can be inserted to compensate for amino acids that have been inserted or deleted through evolution in order to obtain a better sequence alignment score between structurally similar proteins. Despite overall sequence differences that can be observed between proteins, those in the same family generally contain regions that play crucial roles in function and are therefore more strongly conserved. From this, a sequence template can be created which maps out the conserved amino acid residues that are critical to structure and function.The method of scoring include penalties for gaps to prevent the insertion of an unreasonable number of gaps.
By using substitution matrices, we can detect distant evolutionary relationships. Some substitutions are structurally conservative substitutions. They have similar size and chemical properties. They do not have major effects on protein structure. Other substitutions are amino acids that are not similar to each other. In the substitution matrices, "a large positive score corresponds to a substitution that occurs relatively frequently, whereas a large negative score corresponds to a substitution that occurs only rarely" (Berg 169).
Also, we can use database to identify evolutionary relationships. For example, the National Center of Biotechnology Information (www. ncbi.nih.gov)
In some cases a gene may be duplicated and developed into a new gene after mutations are accumulated. However, because the new gene originated from the original gene, it still retains similar domains. Similar domains can be detected by sequence and structural alignments of the repeats by aligning a protein with itself.
Some proteins may contain similar structures but originate from different ancestors. This is known as convergent evolution, where separate proteins evolve through separate pathways and converge on a similar structure and function. In this case, proteins may share similar structures/sequences in regions that prove significant to their function. These proteins often have similar binding sites/active sites. Homology is ruled out due to differences in the overall structures. An example of convergent evolution between our eyes and the eyes of flies. The eyes of flies are from a totally different origin, but has the same function as our eyes.
Structural alignments of homologous RNA sequences can dictate its structure. The comparison of RNA can be a source of studying evolutionary relationships. Though two RNA strands may differ in its base sequences, a similar structure may be obtained through the conservation of base pairing. Though different bases may be involved, base pairing still occurs in the same general locations allowing for similar secondary structures.