Genome transcriptome and proteome in evolution
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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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Genome, transcriptome and proteome in evolution

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Genome transcriptome and proteome in evolution

Genome, transcriptome and proteome in evolution

Xuhua Xia

[email protected]

http://dambe.bio.uottawa.ca


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.


Genome transcriptome and proteome in evolution

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).


    Different types of codon substitution

    Different types of codon substitution

    Table 1.5


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