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Genome, transcriptome and proteome in evolution. Xuhua Xia [email protected] http://dambe.bio.uottawa.ca. Transcription and Translation. Gene 1 Gene 2 Gene 3. Polycistronic mRNA. RNA polymerase. GCC~ tRNA Gly. Ribosome. UCC~ tRNA Gly. Protein.

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transcription and translation
Transcription and Translation

Gene 1 Gene 2 Gene 3

Polycistronic mRNA

RNA polymerase

GCC~tRNAGly

Ribosome

UCC~tRNAGly

Protein

UCC~tRNAGly

Initiation: Met-Gly-...

Elongation: Mn + M  Mn+1

UCC~tRNAGly

ribonucleotide concentration
Ribonucleotide concentration

Measured in the exponentially proliferating chick embryo fibroblasts, 2hrs, in moles 10-12 per 106 cells. The difference is expected to be more extreme in mitochondria.

NNA would seem to be a more efficient codon than NNC

XIA, X., 1996. Genetics 144: 1309-1320.

slide4

EVOLUTIONARY INFORMATION FROM DNA SEQUENCES

GENE

- sequence of DNA (or RNA) that is

essential for a specific function

1. Protein-coding genes

U.S. Dept of Energy Human Genome Program,

http://www.ornl.gov/hgmis

2. RNA-specifying genes

3. Functional DNA elements

  • - regulatory

- structural

Do not use term in text (p.9): “Untranscribed genes” for #3

more on genes
More on genes

“SILENT” GENE

- untranscribed, but potentially functional at DNA level

PSEUDOGENE

  • non-functional DNA with high degree of similarity to a
  • functional gene

How can pseudogenes arise during evolution?

Orthologous genes

- descendants of an ancestral gene that was present

in the last common ancestor of two or more species

Paralogous genes

- arose by gene duplication within a lineage

typical eukaryotic protein coding gene
“Typical” Eukaryotic Protein-coding Gene

5’ UTR?

3’ UTR?

Where is the promoter?

What regions will be present in the mRNA?

Is there an error in this figure?

Fig.1.4

typical bacterial gene organization
“Typical” Bacterial Gene Organization

How many promoters in this region?

How many proteins encoded?

Operon = cluster of co-transcribed genes

Evolutionary advantages of operon organization?

Fig.1.6

protein coding genes
PROTEIN-CODING GENES

“coding strand”

5’ …. ATG GGA TTG CCC GCC …. 3’

DNA

3’ .… TAC CCT AAC GGG CGG …. 5’

“template strand”

5’ …. AUG GGA UUG CCC GCC …. 3’

mRNA

    • DNA usually shown as single-stranded
  • with coding strand in 5’ to 3’ orientation

… so genetic code table can be used directly

amino acids
Amino acids

Fig. 1.9

which amino acid to have in protein
Which amino acid to have in protein?
  • Will it do its job?
    • Amino acid properties and protein function
    • Mutability (Is it likely to mutate into some amino acid that is quite different in physiochemical properties?)
  • Is it abundant in food or cheap to synthesize (if not present in large quantities in food)?
  • Does it have many tRNAs to carry it?
why study amino acid properties
Why study amino acid properties?
  • Protein properties often depends on the properties of their amino acids: Effect of mutation
  • Diagnosis, e.g., protein electrophoresis

Normal

 polypeptide (Hb-A): Val-His-Leu-Thr-Pro-Glu-Glu……GAA

Sickel-cell

 polypeptide (Hb-S): Val-His-Leu-Thr-Pro-Val-Glu……GUA

energetic cost
Energetic Cost

Hiroshi Akashi and Takashi Gojobori, PNAS 99:3695–3700

standard genetic code
Standard Genetic Code

Codon families

have 1 – 6 members

Synonymous and nonsynonymous substitutions

0-fold, 2-fold, 3-fold, 4-fold degenerate sites

0-fold degenerate = non-degenerate

5’ …. AUG GGA UUG CCC CAC …. 3’

genetic code is not universal
Genetic code is not “universal”

Some mitochondria, a few bacteria, a few protists

use a non-standard code

Table 1.4 Vertebrate mitochondrial code

UGA = Trp (instead of stop codon)

AUA, AUG = Met

AGA, AGG = stop codons

Possible implications of different codes in nature?

amino acid dissimilarities
Amino acid dissimilarities

Table 4.7

Grantham’s distance: F(V, P, C)

Miyata’s distance: F(V, P)

amino acid substitution matrices
Amino acid substitution matrices

10 20 30 40 50 60

----|----|----|----|----|----|----|----|----|----|----|----|--

S1 RWFFSTNHKDIGTLYLVFGAWAGMVGTALSLLIRAELSQPGALLGDDQIYNVIVTAHAFVMI

S2 RWLFSTNHKDIGTLYLLFGAWAGVLGTALSLLIRAELGQPGNLLGNDHIYNVIVTAHAFVMI

BLOSUM = BLOcks Substitution Matrixa substitution matrix used for sequence alignment of proteins (to score alignments between evolutionarily divergent protein sequences).

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