Genetics 6: Comparative genomics

Question 1

How was the human genome sequenced in the end compared to original plan

Answer 1

Originally it was linkage mapping, physical mapping and DNA sequencing but Venter said lets do shotgun sequencing : random DNA fragments

Question 2

What is genomics

Answer 2

The study of genes, their interactions and relationships within a species as well as comparison between species

Question 3

Describe the process of whole genome shotgun sequencing

Answer 3

1. Cut the DNA into overlapping fragments short enough for sequencing
2. Clone the fragments in plasmids or other vectors
3. Sequence each fragment
4. Order the sequence into one overall sequence with computer software

Question 4

What is bioinformatics

Answer 4

The application of computational methods to the analysis of large biological data sets. ie DNA sequences.

Question 5

What are the general trends in haploid genome size and number of genes between prokaryotes and eukaryotes and within eukaryotes

Answer 5

1. Prokaryotes tend to have smaller haploid genome size/ number of genes than eukaryotes (5000x less)
2. In Eukaryotes the number of genes is often lower than expected given the size of their genomes
3. There is no relationship in Eukaryotes between the size of genome/ number of genes and phenotypic complexity of organism. Although a threshold has to be hit to get higher organism

Question 6

What is the trend of Gene density (genes per Mb) for prokaryotes vs eukaryotes

Answer 6

1. Prokaryotes have very high gene density compared to Eukaryotes.
2. Within Eukaryotes there is a large variation in gene density with Mammals incl humans have lower gene densities

Question 7

What is unit Mb

Answer 7

Mega base = million base pairs

Question 8

What is the relationship between genome size and the number of genes

Answer 8

None really. Humans have about the same number of genes as something 10x as small

Question 9

What accounts for the differences in gene density between prokaryotes and eukaryotes

Answer 9

Most bacterial genomes have genes for proteins, tRNA, rRNA with remaining as non transcribed regulatory regions. However in eukaryotes lots of DNA neither codes for a protein nor is transcribed into RNA of known function.
-This is up to 10000x more than prokaryotes and can be in genes or outside

Question 10

What is the percentage of repetitive DNA compared to unique sequence in human genome

Answer 10

Repetitive DNA (unrelated to transposable elements < includes transposable elements) takes up 58% where as unique sequence DNA (exons

Question 11

What are the 4 things that make up unique sequence DNA and what % of the human genome are they (smallest to biggest

Answer 11

1. Exons : code for proteins, tRNA or rRNA = 1.5%
2. Gene regulatory sequences=5%
3. Intergenic unique sequence DNA between functional genes (ie pseudogenes that have resulted from mutations making previously repeated genes non functional)= 15%
4. Introns= non translated parts of human genes, varying between genes with some of them transcribed. =20%

Question 12

What are transposable elements + effects + 2 classes

Answer 12

Mobile DNA sequences that can move from one location in the genome to another.
F: They often cause mutations by direct insertion as they are able to insert into many different locations.
- Also can promote DNA rearrangement eg. chromosome deletion, inversions and duplications
2 classes: retrotransposon and retrotransposon

Question 13

How do retrotransposon work

Answer 13

1. Retrotransposon synthesis a single stranded RNA intermediate of the retrotransposon
2. The gene also makes a reverse transcriptase which produces a DNA copy of the RNA strand
3. The reverse transcriptase then can make another strand which makes it a mobile copy.
4. The mobile copy inserts itself into the genome somewhere else

Question 14

How does transposable elements cause unequal crossing over

Answer 14

Homologous transposable elements around the genes of non sister chromatids cause them to align to the wrong transposable regions during meiosis.
As a result of crossing over at this point, one chromatid gets a duplicated gene and one loses the gene

Question 15

How has gene duplication resulted in genome evolution

Answer 15

Through duplication of a gene through evolutionary history a gene family arises.
As the DNA sequence of the genes in the family change, they can have different functions.
Families can spread throughout the genome and code for several proteins, but some can become pseudogenes.

Question 16

Compare dispersed repeat and tandemly repeated multigene families

Answer 16

Dispersed repeat: Multiple copies of the gene organised into clusters on the chromosome that contain functional and pseudogenes. eg. a + b globin

Tandemly repeated: For gene products that are needed in large amounts, there gene family is made of identical tandemly repeated DNA sequences. Eg. Ribosomal RNA, histones.

Question 17

What accounts for the differences in the number of chromosomes between Humans and chimpanzees

Answer 17

A translocation in evolution which resulted in a large metacentric chromosome that resulted from fusion of two acrocentric chromosomes of chimps, as there is some telomerelike+ centromerelike sequences in the middle of our chromosome

Question 18

What is thought to cause the main genomic differences between humans, neanderthals and chimps

Answer 18

The expression of regulatory genes (eg. FOXP2) that allow certain genes (eg. needed for vocalisation) to be activated. Human and Neanderthal FOXP2 is the same sequence but chimp is different

Question 19

What is comparative genomics

Answer 19

Comparative genomics is a field of biology in which genomics of related organisms are compared and the observed differences/similarities can be used as a guide to gene function and evolution.

Question 20

How are humans. neanderthals and chimps related

Answer 20

Neanderthals: closest relative (dead)
Chimps: closest living relative

Question 21

Who discovered transposons

Answer 21

Barbara McClintock