Chapter 19: Eukaryotic Genomes: Organization, Regulation, and Evolution

Key Concepts
191 Chromatin structure is !ased on successive levels o" #$% packing
19& Gene e'pression can !e regulated at any stag, !ut the key step is transcription
19( Cancer results "rom genetic changes that a""ect cell cycle control
19) Eukaryotic genomes can have many noncoding #$% se*uences in addition to genes
19+ #uplications, rearrangements, and mutations o" #$% contri!ute to genome
evolution
,nteractive -uestions
191
.ist the multiple levels o" packing in a metaphase chromosome in order o" increasing
comple'ity
Nucleosomes (10-nm fiber); 30-nm fiber; looped domains (300-nm fiber); coiling
and folding of looped domains into highly condensed metaphase chromosome.
19&
a Give an e'ample o" highly methylated and inactive #$% common in mammalian cells
Barr body-compacted X chromosome in cells of female.
! /ould histone tail deacetylation increase or decrease the transcription o" a gene located
in that nucleosome0
istonetail deacetylation !ould decrease transcription because it !ould ma"e genes
in the nucleosome less accessible.
19(
.a!el the components o" this diagram o" ho1 enhancers, mediator proteins, and
transcription "actors "acilitate "ormation o" a transcription initiation comple'
a distal control elements in enhancer
! acti#ators
c $N%-bending protein
d promoter
e mediator proteins
" transcription factors
g &%&% bo'
h (N% polymerase
19)
a 2he untranslated regions 342R5 at !oth the +6 and (6 ends o" an mR$% may contri!ute
to regulation o" gene e'pression #escri!e their di""erent e""ects
(egulatory proteins may bind to se)uences in the *+ ,&( and bloc" attachment of
ribosomes- thus decreasing gene e'pression. .e)uences in the 3+ ,&( may affect the
length of time an m(N% remains intact- thus either increasing or decreasing gene
e'pression.
! #oes the action o" microR$%s increase or decrease gene e'pression0 E'plain
&hese small- single-stranded (N% molecules (mi(N%s) /oin !ith a comple' of
proteins and act to decrease gene e'pression by base-pairing !ith target m(N% and
either bloc"ing translation or degrading the m(N%.
19+ 2hese diagrams represent signaling path1ays that stimulate 3top diagram5 or inhi!it
3!ottom5 the cell cycle #escri!e the num!ered steps and then e'plain the e""ect o"
mutations that make a hyperactive Ras protein 3top5 or a de"ective p+( transcription
"actor 3!ottom5
0ell-cycle simulating path!ay in#ol#ing (as1 (1) and (2) gro!th factor binds !ith
receptor. (3) 3 protein (as is acti#ated- and (4) sets off protein "inase cascade. (*)
&ranscription factor is acti#ated that turns on gene. (5) 6rtein produced that
stimulates cell cycle. 7utation to the Ras gene may crate a hyperacti#e (as protein
that signals !ithout binding of gro!th factor.
0ell-cycle inhibiting path!ay in#ol#ing p*31 (1) $amage to $N% signals (2) protein
"inase cascade that (3) acti#ates p*3. &his transcription factor turns on gene for (4)
protein that inhibits cell cycle so that damaged $N% does not replicate. % mutation
may result in a missing or defecti#e p*3 transcription factor. &he protein that
inhibits the cell cycle !ould not be produced.
197
8atch the letter o" the description and "ill in the percentage 3listed !elo15 "or each type
o" #$% se*uences "ound in the human genome
1 E'ons 9 R$%:coding
$ protein and (N%-coding se)uences 1.*8
& ,ntrons 9 regulatory
9 $N% related to gene e'pression 248
( 2ransposa!le elements and related repetitive se*uences
B multiple copies of mo#eable se)uences 448
) ;imple se*uence repeats
% satellite $N% in centromeres and telomeres 38
+ .arge:segment duplications
: multiple copies of large se)uences *8
7 4ni*ue noncoding #$%
0 gene fragments- nonfunctional genes 1*8
19<
.ysozyme and =:lacal!umin have similar se*uences !ut di""erent "unctions >oth genes
are "ound in mammals, !ut !irds have only the gene "or lysozyme /hat does this
o!servation suggest a!out the evolution o" these genes0
&he lyso;yme gene- !hich codes for a bacterial infection-fighting en;yme- !as
present in the last common ancestor of birds and mammals. %fter their lineages
split- the gene under!ent a duplication e#ent in the mammalian lineage- and a cop
of the lyso;yme gene e#ol#ed into a gene coding for a protein in#ol#ed in mil"
production.
;tructure ?our Kno1ledge
1 @ill in the ta!le !elo1 to help you organize the maAor mechanisms that can regulate the
e'pression o" eukaryotic genes
.evel o" Control E'amples
Chromatin structure #$% packing into nucleosomesB histone
tail acetylation increases, 1hereas
deacetylation and methylation o" tails
decreases transcriptionB methylation o"
#$% may !e involved in long:term
inactivation o" genes
2ranscriptional regulation 2ranscription "actors 3activators5 !ind 1ith
enhancers, then interact 1ith mediator
proteins and promoter regions to "orm
transcription initiation comple'B repressors
can inhi!it transcriptionB steroid hormones
or other chemical messages may !ind 1ith
receptor proteins, producing transcription
"actors
Cost:transcriptional regulation R$% processing 3alternative splicing, +6
cap and poly:% tail added5B mR$%
degradation !y shortening o" poly:% tailB
removal o" +6 cap, ad miR$% targeting
2ranslational regulation Repressor proteins may prevent ri!osome
!inding so mR$% can !e stockpiled
3a1aiting "ertilization in ovum5B activation
o" initiation "actors
Cost:translational regulation Crotein processing !y cleavage or
modi"icationB transport to target locationB
selective degradation !y proteosomes o"
proteins marked 1ith u!i*uitin
&
a /hat are proto:oncogenes0 Do1 do they !ecome oncogenes0
6roto-oncogenes are "ey genes that control cellular gro!th and di#ision. <hen such
genes mutate to form a more acti#e product- become amplified (multiple copies)- or
ha#e changes in their normal control mechanisms- they may become oncogenes and
produces the uncontrolled ell di#ision that leads to formation of a tumor.
! /hat is the role o" tumor:suppressor genes in the development o" cancer0
&umor-suppressor genes code for proteins that regulate cell di#ision. =oss or
mutation of both alleles of a tumor-suppressor gene may allo! tumors to de#elop.
,sually mutations or other changes must occur both in oncogenes and in se#eral
suppressor genes for cancer to de#elop.
(
a #escri!e a retrotransposon
(etrotransposons are transposable elements that mo#e about a genome as an (N%
intermediate- !hich is con#erted bac" into $N% intermediate- !hich is con#erted
bac" into $N% by re#erse transcriptase- coded for by the retrotransposon.
! Do1 do transposa!le elements contri!ute to genome evolution0
By mo#ing copies of themsel#es around the genome- retrotransposons pro#ide
locations for recombination bet!een different chromosomes. &hey may also
transport genes or e'ons to ne! locations and interrupt coding or regulatory
se)uences.
8ultiple Choice
1 2he control o" gene e'pression is more comple' in eukaryotic cells !ecause
b. gene e'pression differentiates speciali;ed cells. p3*>- p352
& Distones are
a. small- positi#ely charged proteins that bind tightly to $N%. p350
( Deterochromatin
e. is all of the abo#e. p350
) #$% methylation o" cytosine residues
b. may be a mechanism of e'ogenic inheritances !hen methylation patterns are
repeated in daughter cells. p354
+ /hich o" the "ollo1ing appears to !e attached to the nuclear lamina in a precise and
organized "ashion0
d. enhancer regions of acti#ely transcribed genes. p
7 /hich o" the "ollo1ing is not true o" enhancers0
e. &hey are located !ithin the promoter- and !hen comple'ed !ith a steroid or other
small molecule- they release an inhibitory protein and thus ma"e $N% more
accessible to (N% polymerase. p35*
< /hich o" the "ollo1ing is not an e'ample o" the control o" gene e'pression that occurs
a"ter transcription0
c. alternati#e (N% splicing before m(N% e'its from the nucleus p35?
E Cseudogenes are
d. se)uences of $N% that are similar to real genes but lac" regulatory se)uences
necessary for gene e'pression. p3@?
9 /hich o" the "ollo1ing might a proto:oncogene code "or0
c. receptor proteins for gro!th factors p3@1
1F % gene can develop into an oncogene 1hen it
e. does any of the abo#e p3@1
11 /hat is the main reason that prokaryotic genes average 1,FFF nucleotide !ase pairs
1hereas human genes average a!out &<,FFF !ase pairs0
d. 6ro"aryotic gees do not ha#e introns; human genes ha#e many.
1& % tumor:suppressor gene could cause the onset o" cancer i"
e. both a and d ha#e happened.
1( /hat is apoptosis0
a. a cell suicide program that may be initiated by p*3 protein in response to $N%
damage
1) /hich o" the "ollo1ing 1ould you e'pect to "ind as part o" a receptor protein that
!inds 1ith a steroid hormone0
b. a domain that binds to $N% and protein-binding domains
1+ % eukaryotic gene typically has all o" th "ollo1ing associated 1ith it except
b. an operator
17 /hat are proteasomes0
d. enormous protein comple'es that degrade unneeded proteins in the cell
1< 2issue plasminogen activator 32C%5 is a protein 1ith three types o" domains One o"
each o" these types is "ound in the protein6s epidermal gro1th "actor, "i!ronectin, and
plasminogen /hat is a likely e'planation "or this0
c. &he gene for &6% arose by se#eral instances of e'on shuffling from the other three
genes.
1E /hich o" the "ollo1ing 1ould most likely account "or a "amily history o" colorectal
cancer0
e. inheritance of one mutated APC allele that regulates cell adhesion and migration
19 /hich o" the "ollo1ing !est descri!es 1hat pseudogenes and introns have in
common0
c. &hey are not e'pressedAthey do not produce a functional product.
&F Do1 is the coordinated transcription o" genes involved in the same path1ay
regulated0
e. &he gees ha#e the same combination of control elements in the enhancer that bind
!ith the particular acti#ators present in the cell.