Lecture 7: Comparative Genomics Flashcards
What is comparative genomics?
Addressing biological questions through the comparison of genomes from different species
Why can info on one organism have application for another?
Because all modern genomes arise from a common ancester
What does genomic data include and what can we determine the relationship between?
transcription profiles and genotype and phenotype.
Why wasn’t sequencing the human genome enough?
Thought sequencing the human genome would enable us to cure cancer in 10 years. Difficult to study our evolution from fossil records as the record is patchy. Don’t understand a lot of things from genes such as how a protein would look after it is folded properly or what the isoforms after alternative splicing are.
What other species genomes had already been sequenced and by what method?
yeast, fungi, worm, fruit fly. by shotgun sequencing
What genomes have been sequenced since then?
11 drosophila, 7 ant species, over 57 insect species, 50 bird genomes and others.
What do genome sequences of closely related species allow?
The study if evolutionary changes within a defined taxa.
How can comparing genomes help us? Give 6 reasons
1) assess the relationship between species and build phylogenetic trees
2) Identify previously non-annotated elements of genes eg exons and assign function to them
3) We know if a gene in a fly is for regulating leg movement, the human equivalent probably does the same as essential functions are usually conserved across species
4) Identify genes important to the evolution of species
5) Identify functional areas of non-coding DNA as highly conserved genomic areas are likely to be functional
6) Identifying genes important for key biological functions
How can genes important for specific functions be identified?
Screening mutants in mouse, drosophila, yeast for human gene homologs
Describe what was found upon comparison of human and mouse genomes.
Found greater sequence identity between exons than introns. At the starts and ends of exons there is very high conservation as the splicing out of introns is highly conserved as this can be detrimental.
Describe the gene family evolution in drosophila
From a tree showing the number of gene loses and gains found 17 duplicated genes reach fixation per million years (similar to humans and yeast). gene number doesnt change much but there is high turnover of genes. accelerated evolution found in reproduction associated gene families as they mutate fast.
Give an example of where comparative genomics have revealed strong natural selection
Human gene compared to rat and mouse and found over 500 regions more than 200bp where no differences. Majority also in chicken and dog genomes. Sequence identity over 95%. 256 areas where no evidence of transcription.
What areas are human accelerated regions associated with?
CNS and development
What do human accelerated regions include?
Positive regulation of transcription, forebrain development, epithelial cell proliferation.
What is increased brain size in mammals associated with?
size variations in gene families with cell signalling, chemotaxis and immune related functions.
