Exam 3: Genomes Evolution and Genomics and Proteomics

Question 1

Genomics involves the study of 4 things…

Answer 1

1. Gene Sequences
2. The mechanisms that regulate gene activity
3. The interaction between genetic factors and between genetic and nongenetic factors
4. Comparisons between and within species, which are designed to reveal the functions of newly discovered proteins, to elucidate evolutionary relationships, and to reveal insights into the workings of biological systems

Question 2

The term “genome” is used in two contexts. What are they?

Answer 2

1. The organism’s entire DNA sequence
2. The organism’s entire collection of genes

Question 3

1. An organism’s C value represents…
2. The C Value Paradox=

Answer 3

1. How much DNA that organism has in a diploid cell
2. More DNA does not mean a more complex organism

Question 4

There is no relationship between…

Answer 4

Genome Size And Organism Complexity

Question 5

What are Gene Families?

Answer 5

Genes that came from a common ancestor but have had time to diverge from each other through sequence changes that occurred after the duplication. Can cause large duplications.

Question 6

What are pseudogenes?

Answer 6

When copies have been rendered nonfunctional by mutations

Question 7

What does homolous mean?

Answer 7

Genes that are related through evolution

Question 8

What are orthologs?

Answer 8

Homologous genes that are found in two different species and evolved from a common ancestor

Ex. many of the genes that organize your physical development to see that the proper body parts grow in the proper places are homologous to the genes that perform the same function in the mouse or fruitfly

Question 9

What are Paralogs?

Answer 9

Two genes within a single organism that are homologous and arose from a duplication sometime in the evolutionary past

Ex. the alpha globin, beta globin, gamma globin and myoglobin genes arose from a duplication and subsequent mutations

Question 10

Sometimes all members of the gene family perform…

Answer 10

The same function

Ex: All member of the globin gene family carry oxygen

Question 11

Sometimes the new copies evolve…

Answer 11

New functions through sequence changes

Ex: Human angiogenin (promotes growth of blood vessels) diverged from ribonuclease (digests RNA); their functions within the cell are now quite different

Question 12

What are Unique Sequences?

Answer 12

Found only once in the genome

30-75% of the genome, depending on the organism

(~53% of human genome)

Much of this is protein-coding genes or regulatory sequences

Question 13

What is highly Repetitive DNA?

Answer 13

Repeated sequences range from 5-300 bp

5-45% of the genome , depending on the organism

(6% of the human genome)

Up to 10,000 copies per genome

Often found in heterochromatin at centromeres and telomeres

Question 14

What is moderately Repetitive DNA?

Answer 14

Repeated sequences range from 150-300 bp

1-30% of the genome, depending on the organism

(>40% of the human genome)

10 – 1,000 copies per genome

Most repeated sequences do not contain genes, but the moderately repetitive sequences include the genes for histone proteins (~20 copies), some of your rRNA (200-300 copies) and some tRNAs

Question 15

Repetitive DNA may be…

Answer 15

Tandem or Interspeed

Question 16

What are tandemly repeated sequences?

Answer 16

Back-to-back repeats with no intervening sequences

Question 17

What are interspersed repeat sequences?

Answer 17

Scattered throughout the genome,

often due to the action of transposable elements:

Short Interspersed Elements (SINEs) = Approx 200-300 bp. Most common = the Alu repeat, ~200-300 bp, several million copies per genome

Long Interspersed Elements (LINEs) = Several thousand bp

Question 18

Explain the Concept of Transposable Elements

Answer 18

Transposable elements (aka transposons) can move from one place to another within the same cell’s DNA

They can “cut and paste,” (nonreplicative transposition) and leave their original place to insert elsewhere, or they can make a copy of themselves and “copy and paste” (replicative transposition) themselves into another location

Approx. 45% of the human genome has come from transposon

Question 19

Explain Structural Genomics

Answer 19

Structural genomics involves sequencing genomes and making comparisons between species

These comparisons can be focused on evolutionary relationships between organisms

They can focus on biological issues within organisms, such as why one organism can metabolize a specific macromolecule and another species that is similar in other respects cannot

Genomic researchers construct genomic maps

Question 20

What are the two types of genomic maps and which one came first?

Answer 20

Genetic map units are recombination frequency (Rf), centiMorgans (cM) or map units (m.u.). For a genetic map, you only need to know the sequence of the two elements you are studying, so you can see which alleles the parents and offspring possess

Genetic Maps Came First

For a physical map, you must have sequenced the entire region

Physical map units are basepairs (bp)

Question 21

Describe physical maps in more detail

Answer 21

Physical maps display distances in basepairs–physical maps display distances between genes more clearly than genetic maps do

Physical maps are often constructed by using enzymes to cut the DNA into fragments, inserting the fragments into vectors (i.e. cloning the fragment into a vector), then sequencing the fragments

The vectors used have sequences that readily bind a certain set of PCR primers right next to the insertion site, so you can easily amplify and sequence your inserted fragments

Question 22

If your clone overlap eachother in a physical map then you know…

Answer 22

Then you know you are generating gap-free sequence, because the sequence of each clone starts with a sequence you saw at one end of the neighboring clone, then extends past that neighboring clone and ends in a sequence you will find at the end of another clone

Question 23

What are the Discrepancies Between Genetic Maps And Physical Maps

Answer 23

Sampling error (esp. if the study had a small population) can cause the genetic map to position genes improperly

The small study population may just happen not to include a representative percentage of families in which there was recombination between two genes

Question 24

What does functional genomics focus on?

Answer 24

Functional genomics focuses on the regulation of gene activity, the proteins that get produced by the genome, and what they do

Question 25

What do fuctional genomic researchers study?

Answer 25

Genomic researchers study the promoter region sequences, transcription factors that regulate gene activity, and the molecules that regulate production of those transcription factors

Genomic researchers search newly sequenced genomes for genes, by identifying the consensus sequences you see in genes—transcription/translation initiation sites, intron/exon boundaries, transcription factor binding sites, polyadenylation signals, etc.

Question 26

Give a breif description of the purpose of gene microarrays

Answer 26

In a microarray, millions of different probe sequences are immobilized and denatured (usually on a glass slide or silicon wafer)

Many specific applications, including identifying which gene variants an organism possesses, which genes are active in that tissue at that time, identifying gene expression changes in tumors, the effects of drugs on gene expression

Question 27

Explain if full detail how microarrays work

Answer 27

In a microarray, millions of different probe sequences are immobilized (usually on a glass slide or silicon wafer)

These sequences are denatured (single-stranded), so that any probes that have complementary sequences will bind (hybridize) to them

The array is incubated with genomic DNA or a cDNA pool from the tissue of interest that has been labeled with fluorescent molecules, so you can see which sequences in the microarray the sample binds to

Many specific applications, including identifying which gene variants an organism possesses, which genes are active in that tissue at that time, identifying gene expression changes in tumors, the effects of drugs on gene expression

Question 28

Explain how reporter genes work

Answer 28

Genomic researchers studying gene expression patterns sometimes replace the coding sequence of the gene of interest with a “reporter gene”—often green fluorescent protein (GFP)

You can quantitatively determine the rate of gene activity by measuring how green the subject gets

Question 29

Bioinformatics combines molecular analysis and computerized data processing to:

Answer 29

Provide databases of normal sequences, enabling comparison between species

Provide databases of genetic variants within a species, enabling researchers to identify risk-influencing alleles for diseases

Mine genomic sequences to identify the genes, miRNAs and other important elements that are present

Question 30

Explain how metagenomics works and give an example of how its used

Answer 30

Metagenomics involves identifying the sequences of all the organisms in an environment

ex. analyzing microbes in a soil sample

Ex. Global Ocean Sampling Expedition followed Darwin’s route and took water samples from various depths

Discovered 6 million new proteins, including 1700 new protein families

Ex. analyzing gut microflora of obese people found that the balance of Bacteroides and Firmicutes bacteria shifts (increased Firmicutes) versus lean people

Transplanting colonic bacteria from obese mice to lean mice—the lean mice harvested more energy from their food and increased body fat

Question 31

Hybridization Studies Suggest That Chimpanzees Are Our Closest Genetic Ancestor. What did they find in their studies specifially?

Answer 31

Research suggests that humans and chimps began to diverge as much as 7 to 13 million years ago, but continued to intermingle, then finally completed the divergence 5 to 6 million years ago

With 3.3 billion bp in the human genome, 4.2% represents 138,600,000 basepairs at which we differ

Question 32

How is Mitochondrial DNA Used To Trace The History Of Human Females?

Answer 32

Everyone who is related through a line of female relatives has the same mitochondrial DNA sequence. It does undergo recombination like DNA does.

Ex. your maternal grandmother, your mother and your mother’s sisters and brothers, you and all your sisters and brothers, all your maternal aunts’ children, male and female, all those female cousins’ children, male and female

One drawback—we all inherit all our mitochondria from our mothers, so mitochondrial sequence differences only reflect the history of women

Question 33

How does the Y Chromosome Sequences Reflect The History Of Men?

Answer 33

For the most part, there is no recombination between the X and Y chromosomes (exception—the pseudoautosomal regions)

All males who are related to each other through an uninterrupted line of male relatives have the same Y chromosome sequences

It is estimated that the Y chromosome from Genghis Khan and his sons is present in populations that range throughout the entire Mongolian Empire (When the king had sex with everyone) in China

Question 34

How has the The “Smart And Sexy” X Chromosome Play An Important Role In The Evolution Of Human Cognition?

Answer 34

The X chromosome contains far more genes that are critical for brain and intellectual development than any other chromosome does

In addition, the X chromosome also contains several genes that influence sperm count and motility

Having a good X chromosome meant the male could find resources and avoid predators more effectively, i.e. live longer and healthier

In addition, having that good X got you selected more often for mating (whether because you were smart or because you were round-headed and cute)