lecture 5- Introduction to BioinformaticsComputational Genomics Flashcards
Why sequence information matters?
Amino-acid sequence determines protein structure and function
amino acid sequence–>structure–>function
Similar sequences have similar structures and in turn, similar structures have similar function
Proteins are the building blocks of the cell and play a central role on the biological processes that sustain life
Analysis of biological sequences can help us identify sequence elements and programmes controling processes involved in life, including the unravel DNA function
How is sequence analysis useful?
for
-organism identification
-evolution and phylogenetics
-TF binding sites
-gene prediction
-identifying protein families
-recognising protein domains and functions
what is Sequence comparison
Sequence comparison and the ascertainment of sequence similarity is central to all computational genomics.
Sequence similarity imply function similarity.
Why genes in different species have similar DNA?
Shared evolutionary history: Species that descend from a common ancestor will share stretches of conserved DNA
Evolutionary convergence: Two species may evolve similar phenotypes in response to the same environment. DNA sequences of both species may converge
Why genes with similar sequence tend to have similar function?
Sequence similarity –> Evolutionary relationship –> Related function
Gene sequences after speciation events will accumulate random mutations. Over many generations sequence divergence between the species will increase.
The same gene in both species will nevertheless conserve sequence similarity to preserve gene function
Genes with similar function but low sequence similarity may code proteins with similar 3D structures. Ultimately what is evolutionarily conserved is protein structure because structure impinges function.
what are orthologs?
Orthologs: Genes in the genomes of different species that are related because descend from a common ancestor
what are paralogs?
Paralogs: Genes in the same genome that are related due to a duplication event in the last common ancestor
what are homologs
Homologs: Any paralog or ortholog genes.
how are Alpha- and beta-globin amino acid sequences different and similar
Alpha- and beta-globin amino acid sequences are considerably different. However, their secondary structure is relatively conserved.
Sickle cell anaemia is caused by a mutation in β-globin
Why genes with similar sequence tend to have similar function?
Sequence similarity –> Structure similarity –> Related function
Convergent evolution occurs when two distinct species evolve similar traits, for example due to shared environment. Similar traits may result from proteins with similar function. Protein with similar function tend to have similar structure and similar sequence
Convergent evolution of flavone synthases
Flowering plants typically contain two structurally and catalytically convergent types of flavone synthases, that show dissimilar DNA sequence
Flavone production in most plants is catalysed by membrane bound cytochrome P 450 FNS2.
Plants in the Apiaceae employ a soluble type I FNSs belonging to the non-homologous 2-oxoglutarate-dependent dioxygenase family.
Summary
Similar sequences have similar structures and in turn, similar structures have similar function
Sequence similarity may have an evolutionary origin when the compared sequences have a common ancestor or may arise independently in two species due to evolutionary convergence.
Sequence similarity may occur due to speciation in orthologs or due to gene duplication in paralogs. Both orthologs and paralogs have an evolutionary origin and are termed homologs.
Two sequences that are similar due to evolutionary convergence are termed analogs.
Quiz: Two genes may have similar function if they share high
Homology
Homology may arise due to orthology and paralogy. Both refer to loci shared by descent. The best answer is homology.
What is sequence alignment
The goals of an aligner is to distinguish regions of equivalence from regions of difference, avoid meaningless alignments, and find homologous regions due to a common evolutionary ancestor.
Local and Global Alignment
Global alignment finds the best possible alignment between two sequences across the full range of the sequence
-Global alignment applicable to very similar sequences with approximately the same length, e.g. same gene in closely related species.
Local alignment finds regions of similarity between two sequences
-Local alignment is useful when only parts of a sequence are related, e.g. proteins that share common domains but otherwise completely unrelated. Domains are conserved amino acid sequences that carry out similar functions