BIOL 1201 Chapter 21

Genomics & Genome Organization

genomics

Chapter 21 focus: mostly about ____________________________.

genomes; genes; DNA; grouped

Genomics = study of:

○ The structure of ____________________________

○ What ____________________________ are in them

○ What other types of ____________________________ are in them

○ How they are ____________________________ and organized

bioinformatics

Genomics is a part of ____________________________.

data; sequences

Bioinformatics = a larger field involving:

○ Processing large ____________________________ sets

○ Includes things like genome ____________________________

proteome; transcriptome

Bioinformatics can include:

○ Looking at protein sequences → the ____________________________ of an

organism

○ Looking at all mRNA sequences → the ____________________________ of an

organism

seuqnecing

Genomics starts with ____________________________ the DNA.

DNA

Goal: sequence all of the ____________________________ in an organism.

ten; 1990; 2003; human genome; individual; United States; Jim Watson; Francis Collins

Human Genome Project (HGP):

○ Planned as a ~_______-year project.

○ Actually ran from about _______ to _______.

○ Goal: sequence the entire ____________________________

____________________________.

○ Sequenced the genome of a single ____________________________.

○ Started as a ____________________________ government project (NIH).

○ Led initially by ____________________________ (of Watson & Crick) and

____________________________ ____________________________ (still a

head of NIH).

3; 6.4; 6.4; 3.2

Designed to:

○ Cost about $__________ billion over ten years.

○ Sequence all _______ billion bases in the diploid human genome.

■ Diploid genome: _______ billion bases

■ Haploid genome: _______ billion bases

Thomas Hunt Morgan

The HGP strategy started from existing information:

○ Linkage maps / cytogenetic maps from crossing over experiments.

○ Built from work like ____________________________

____________________________ ____________________________

(Drosophila crossing-over experiments).

genes; restriction enzymes

Strategy:

○ Use linkage information (how far apart different

____________________________ are on a chromosome).

○ Divide chromosomes into smaller, overlapping fragments.

○ Use ____________________________ ____________________________

(enzymes that cut at specific DNA sequences) to cut DNA.

300-400; thousand

Fragments must be relatively small because:

○ Early sequencing could read only ~– bases at a time.

○ Now can handle up to a few ____________________________ bases at a time.

○ Fragments are cut with overlap so they can be matched and ordered.

time; labor

This approach was:

○ ______-intensive

○ ____-intensive

1998; Craig Venter

Around _______ (late 1990s), ____________________________

____________________________ (Celera) entered with a private company.

shatter; different; computer

Around _______ (late 1990s), ____________________________

____________________________ (Celera) entered with a private company.

300

Claims:

○ Could do it for about $__________ million (≈ 1/10 the cost of the public project).

○ Could finish before the original Human Genome Project.

parallel; 98-99

Result:

○ Two human genome projects (public NIH vs. private Celera) ran

____________________________.

○ Both ended up with ~–% of the genome sequenced (last few % are very hard).

○ Even scientists could not easily tell which had sequenced more.

Clinton; Collins; Watson; Craig Venter; same

Political resolution:

○ President ____________________________ brought

____________________________, ____________________________, and

____________________________ ____________________________ to the

White House.

○ After a marathon meeting (~24 hours), they held a joint press conference.

○ Announced that both groups had “finished” sequencing the human genome at

the ____________________________ time.

3; 5

Now, thousands of whole-genome sequences exist:

○ Done for many organisms (estimated __________ to __________ thousand

organisms or more).

scientific articles; public; research

PubMed & genome databases:

○ PubMed is used to look up ____________________________

____________________________.

○ A subdivision allows viewing any genome sequence obtained with

____________________________ funding.

○ Many researchers use these sequences in ____________________________

projects.

domains

One application: looking for patterns in sequences that predict folding or _______.

proteins; genome; cow; corn; human; amino acids

Example: WD40 domain:

○ Identified by comparing many related ____________________________ and

their ____________________________ sequences.

○ Proteins from __________, __________, and __________ all show the same

pattern.

○ Certain ____________________________ ____________________________

are spaced in a characteristic way → leads to a common folding pattern (beta

sheets forming spiral structures).

similar; mitosis; peroxisomes

Another application: finding families of proteins:

○ Thousands of proteins can be compared and clustered.

○ Color clusters indicate proteins with ____________________________

functions.

○ Sequence comparison can identify groups:

■ e.g., proteins involved in ____________________________

■ e.g., proteins involved in ____________________________ (like

peroxisomes)

proteomic; bioinformatics

This type of analysis falls under ____________________________ (study of all

proteins) and is a subset of ____________________________.

gene chips

Another modern use of genomic information: ____________________________

____________________________ (“gene chips”).

sequence; messenger RNAs

If you know:

○ The genomic ____________________________

○ Which parts of the genome produce ____________________________

____________________________ (mRNAs)

printers; mRNA

You can:

○ Use high-resolution ____________________________ to print many short DNA

sequences onto a small × chip.

○ Each spot on the chip corresponds to a specific

____________________________ (or mRNA).

messenger RNA; ssRNA; cell; mRNA

Experiment:

○ Take an unknown cell and isolate its ____________________________

____________________________.

○ Radioactively label the mRNA and wash it over the chip.

○ Single-stranded mRNA will base-pair with complementary

____________________________ or ____________________________ on the

chip.

○ Radioactive spots on the chip show which ____________________________

are being expressed in that cell.

20; 2; Human Genome Project

Notes:

○ Originally extremely expensive (~$__________ thousand per chip).

○ Now much cheaper (~$– thousand).

○ Method is still being refined; has some sloppiness but is getting more precise.

○ It is an outgrowth of the ____________________________

____________________________ ____________________________.

small; eukaryotic; larger

Genome size:

○ Bacteria and Archaea typically have ____________________________

genomes.

○ The largest bacterial/archaeal genome is still smaller than the smallest

____________________________ genome.

○ Eukaryotic genomes are usually much ____________________________

overall.

1500; 7500; more

Gene number:

○ Most bacteria have between about _______ and _______ genes.

○ Eukaryotes usually start around the middle of that range and go up to many

____________________________ genes.

gene density; eukaryotes

Gene density:

○ Increase in gene number is not as large as increase in total genome size.

○ Therefore, eukaryotes have more DNA per gene → lower

____________________________ ____________________________.

○ Much more DNA between genes in ____________________________.

protein; RNA

Modern definition:

○ A gene = stretch of DNA that codes for a ____________________________ or a

specific ____________________________ (e.g., rRNA, tRNA).

proteins; RNA; 1.5

Human genome composition (key result of the HGP):

● Exons (expressed parts of genes):

○ Code for ____________________________ and specific

____________________________.

○ Make up only about _______ % of the genome.

5

Introns (noncoding parts within genes):

○ Spliced out of transcripts.

○ Make up about _______ % of the genome.

repressor; enhancers; 1.5

Regulatory sequences:

○ Include binding sites for ____________________________,

____________________________, and other control proteins.

○ Control the expression of the _______ % of coding DNA.

○ Occupy a large fraction of the genome.

not

Unique noncoding DNA:

○ Does ___ code for proteins or known specific RNAs.

○ Appears only once (no repeats).

58; thousands

Repetitive DNA:

○ More than _______ % of the genome.

○ Noncoding, but repeated many times.

○ Some repeats are long stretches (thousands of bases) repeated many times.

○ Others are short sequences (like 5–10 bases) repeated

____________________________ of times.

DNA (not-genes); eukaryotes; eukaryotes

Overall:

○ ~98% of the genome is ____________________________ (does not code for

specific proteins or RNAs).

○ This huge fraction of noncoding DNA is a feature especially of

____________________________.

○ In bacteria: very little noncoding DNA, few/no introns.

○ In Archaea: a bit more noncoding DNA, but far less than in

____________________________.

transposable elements; transposable elements

Repetitive DNA can be divided into:

○ Related to ____________________________

____________________________

○ Unrelated to ____________________________

____________________________

transposable; jump around; identical twins

ALU elements:

○ A specific type of repetitive DNA in humans.

○ Do not code for proteins.

○ Are ____________________________ elements → they can

“____________________________” in the genome.

○ Change rapidly enough that even ____________________________

____________________________ can sometimes be distinguished by their ALU

patterns (useful in forensic genetics).

44; sequences

Transposable-element–related DNA makes up about _______ % of the genome.

○ These sequences are actively changing over time.

○ They can insert almost anywhere, including occasionally in

____________________________.

Barbara McClintock;

Transposable elements were discovered by ____________________________

____________________________.

corn; coloration

She studied ____________________________ and noticed:

○ Differences in ____________________________ patterns of kernels even on the

same ear.

copied; randomly; RNA; reverse transcriptase; DNA; genome

She hypothesized transposition events:

○ Direct transposition:

■ A part of the genome (a transposon) is

____________________________ and then inserted

____________________________ somewhere else in the genome.

■ If insertion affects a color gene, it changes kernel color in that region.

○ Retrotransposition:

■ A random part of the genome is transcribed into

____________________________ (not necessarily mRNA).

■ ____________________________ ____________________________

(enzyme present in our cells) converts that RNA back into

____________________________.

■ That new DNA copy is then inserted elsewhere in the

____________________________.

genome

In both cases:

○ A copy of some genomic region is inserted into a new

____________________________.

○ This is happening in your genome right now.

insane; Nobel Prize

Initially, her ideas were considered ____________________________, and she had

trouble publishing.

○ Later, others confirmed her work in many organisms, including humans.

○ She eventually won the ____________________________

____________________________ for this discovery.

kitchen suddenly; apoptosis; gene duplication

The genome is therefore dynamic, not perfectly stable:

○ Large pieces of DNA can literally move, like a

“____________________________ ____________________________ jumping

into the living room.”

○ If damage is severe, the cell dies via ____________________________

(programmed cell death).

○ Transposition can also drive evolution through

____________________________ ____________________________.

gene duplication

One major outcome of transposition: ____________________________

____________________________.

ribosomes; hundreds; thousands; transposition; same

Ribosomal RNA (rRNA) genes:

○ rRNAs are long RNAs that form part of ____________________________.

○ Not encoded in just one place; there are ____________________________ to

____________________________ copies of rRNA genes.

○ Organisms need many ribosomes → many copies of rRNA genes.

○ This extra copy number is believed to result from

____________________________ events.

○ In rRNA, duplicated genes remain essentially ____________________________

(all ribosomes are the same).

gloin

Another classic gene family: ____________________________ (hemoglobin genes).

beta; alpha

Adult hemoglobin:

○ Contains an ____________________________ subunit and a

____________________________ subunit.

gene duplication

There are many globin-related genes with slightly different sequences (different Greek

letters).

○ These variants arose by ____________________________

____________________________ and mutation.

42; 37

Sequence homology examples:

○ Alpha vs. beta: about _______ % homologous.

○ Alpha vs. epsilon or others: ~– % homologous.

oxygen; mother’s bloodstream

Functional specialization:

○ Fetal and embryonic hemoglobins bind ____________________________

more strongly than adult hemoglobin.

○ This helps a fetus obtain oxygen from the ____________________________

____________________________.

globin; duplication; mutations; alpha; beta

Evolutionary model:

○ Start with a single ____________________________ gene.

○ Gene ____________________________ creates two copies.

○ Each copy independently accumulates ____________________________.

○ They diverge into the ____________________________ and

____________________________ lineages.

○ Further duplications within each lineage produce multiple specialized globins with

different O2 affinities and roles.

TPA; plasminogen; fiber nekton; epidermal growth factor

Transposition can also move exons around → exon shuffling.

● New genes can be created by combining exons from different ancestral genes:

○ Example: ____________________________ (TPA) gene.

■ Its exons can be traced back to:

■ ____________________________ gene

■ ____________________________ gene

■ ____________________________

____________________________

____________________________ gene

transposition

DNA and protein sequence analysis shows that:

○ Exons from these different genes were brought together by

____________________________ events.

○ Resulted in a new gene encoding a protein with combined functional domains.

2; 12; 13; centromere; telomere

Beyond transposition and point mutations, whole chromosomes can be reorganized

over evolutionary time.

● Example: Human vs. Chimpanzee:

○ Human chromosome _______ appears to be a fusion of chimpanzee

chromosomes _______ and _______.

○ Evidence:

■ Presence of two ____________________________-like regions in

human chromosome 2.

■ Presence of internal ____________________________-like sequences.

16; human

Example: Human vs. Mouse:

○ Human chromosome _______ contains genes found on four different mouse

chromosomes.

○ Indicates that mouse chromosomes were rearranged and fused into a different

pattern in the ____________________________.

longer

These rearrangements:

○ Are not happening all the time in each cell (unlike transposition).

○ Occur on ____________________________ timescales as lineages diverge.

evolutionary trees

Comparative genomics data (sequences, rearrangements) are used to build

____________________________ ____________________________.

5; 65

Examples of divergence estimates:

○ Humans and chimpanzees diverged about _______ million years ago.

○ Humans and mice diverged about _______ million years ago.

globin; Alu

Different parts of the genome evolve at different speeds:

○ Some genes (e.g., ____________________________ genes) are highly

conserved.

○ Others (e.g., regions like ____________________________ elements) evolve

very fast.

slowly; rapidly; dates

Result:

○ Using ______ changing genes gives one estimate.

○ Using _____ changing regions gives slightly different estimates.

○ Overall branching pattern (e.g., chimp closer to human than mouse) does not

change, but the ____ can shift.

anterior; posterior; mouse

● Another major finding: some developmental genes are extremely conserved.

● These include cytoplasmic factors / homeotic genes:

○ Control body plan (which parts become ____________________________ vs.

____________________________).

○ Similar genes control A–P patterning in flies and in other

____________________________ animals.

evolution

These developmental genes are often more conserved than many structural genes (like

hemoglobins).

○ This high conservation affects how we build and interpret

____________________________ trees.

○ Raises questions about which genes to prioritize (highly conserved vs. rapidly

evolving) in analyses.

bacteria; archaea; eukaryotic

The legacy of the Human Genome Project has become the many genomes era:

○ Thousands of genomes sequenced, especially

____________________________ and ____________________________.

○ Hundreds to thousands of ____________________________ genomes have

also been sequenced.

some

These data sets:

○ Reveal genome organization, transposition, and chromosomal rearrangements.

○ Allow reconstruction of ____________________________ relationships and

divergence times among organisms.