Fig. 7.13Genome = Genic + Intergenic (or non-genic)

Eukaryotic genomes: composition of human genome

Fig. 7.5

Chromosome architecture

Centromere:in humans, 1500-30,000 copies of 171 bp tandem repeat (alphoid DNA)

Telomere:100’s copies of tandemly repeated motif TTAGGG, short 3’ overhang

Constitutive heterochromatin:- chromatin which is always densely packed & inert- transcriptionally inactive, virtually no genes- centromeres, telomeres, Y chromosome (most)

Facultative heterochromatin: -chromatin which is usually highly condensed -may contain some genes which are expressed in some cell types or life cycle stages

Fig. 7.19

Most genes are in non-repetitive DNA regions…

(i) in tandem arrays (eg. rRNA genes, globin genes)

(ii) dispersed (eg. actin genes on different chromosomes)

BUT low-to-mid repetitive DNA fraction includes multi-gene families

Where are genes located within nuclear genomes?

Fig.7.11

1. Nonsense mutations…

2. Truncation - part of gene missing because of deletion or rearrangement

3. Insertion of transposon (or retrotransposon) into coding or regulatory sequences (of duplicated gene)

How might pseudogenes arise?

PSEUDOGENES = defective, non-functional gene copies

(or point mutation within initiation codon)

or frameshift mutations

“Processed pseudogenes” - cDNA copy (lacking introns & promoter) integrated into genome

Fig. 7.20

Transcription

Reverse transcription

Re-integration

Make-up of 50 kb segment of human chromosome 12

Fig.7.12

(i) LINES (long, interspersed nuclear elements)- non-LTR retroelements, encode RT- in human genome > 1 million copies~ 20% total genome !!

(ii) SINES (short, interspersed nuclear elements)- do not encode RT- eg Alu repeats derived from 7SL RNA copies- in human genome > 1.5 million copies~ 12 % total genome

Fig. 9.15 & Table 9.3

See Fig. 4.15c Use of Alu repeats in clone fingerprinting

Interspersed repetitive DNA (typically non-genic, but can occur within introns)

(iii) LTR retroelements - retrotransposons, encode reverse transcriptase- in human genome >500,000 intact/degenerate copies

~ 8% of total genome

Fig. 9.14

long terminal repeats

(iv) DNA transposons- encode transposase, DNA mode of movement- in human genome >300,000 copies (~ 3% total genome)- but notable in plant and bacterial genomes

- transposons used as mutagenesis tools (for info about gene function)

Nobel prize 1983

Ac/Ds transposons: variegated pigmentation in corn kernels

Fig. 9.19

Alberts Figure 4-17

Composition of Human Genome

Dispersed repeats comprise ~ 45% of human genome !!

Maybe even higher, because “old” repeats degenerate & their origin is not recognizable...

Retroviral, retrotransposon/retroelement sequences make major contribution to human genome size

Microsatellites, minisatellites, see p. 217-8

[A & B] - retrovirus invades genome & copies are spread

- copies degenerate over time into “relics” (eg. lose env gene)

How does genome acquire so many copies of retroelements?

[C & D] - if RT present, cDNAs of retroelement RNAs & cellular RNAs, in the case of [D], made & integrated into genome

Fig. 9.14 & 9.15

Retrovirus particle

gag = group specific antigen

env = viral envelope protein

“Beyond defining proteins, the DNA bases highlighted by ENCODE specify landing spots for proteins that influence gene activity, strands of RNA with myriad roles, or simply places where chemical modifications serve to silence stretches of our chromosomes.

- “found that 80% of the human genome serves some purpose, biochemically speaking”

“ [this decade-long work] sounds the death knell for the idea that our DNA is mostly littered with useless bases.”

ENCODE (Encyclopedia of DNA Elements) data reported Sept 2012

Pennisi Science 337:1161, 2012

Alberts Fig.1.38

Arabidopsis

C-value paradox:

- in certain cases, lack of correlation between morphological complexity and genome size

VARIATION IN GENOME SIZE AMONG ORGANISMS

log scale: # bp per haploid genome

NB: Error in Fig.7.14 in Brown 3d ed. in placement of bars for insects-to-plants

Fig.7.14

Duplicated sequences in Arabidopsis genome

chr I

chr II

chr III

chr IV

chr V

Nature 408:796, 2000

- includes segmental duplications (& many multi-gene families)

(p.577)

Regions from different mouse chromosomes (indicated by the colors in B) show conserved synteny (gene order) with the indicated regions of the human genome (A). For example the genes present in the upper portion of human chromosome 1 (orange) are present in the same order in a portion of mouse chromosome 4. Alberts Figure 4.18

Regions of synteny between human and mouse genomesSynteny = conserved gene order among organisms

Comparative genomics

What fraction of identified human genes are shared among organisms?

Fig.7.18

Fig. 7.17

Do eukaryotes differ in the types of genes they have?