Mendelian inheritance (1866) ● Law of Segregation ● Law of Independent Assortment ● Law of Dominance

王擎天, 朱柏昇, 張家瑜

Mendelian inheritance (1866)

● Law of Segregation

● Law of Independent Assortment

● Law of Dominance

Gregor Mende (1822 - 1884)

wikipedia

Law of segregation(分離定律)

● Every individual organism contains two alleles(等位基因) for each trait

● Alleles segregate during meiosis each gamete contains only one of the alleles

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Meiosis

Gametes

Law of Independent Assortment(獨立分配定律)

● The separation and combination of genetic elements

that control different

traits do not interfere

with each other

Law of Dominance (顯性法則)

● Recessive alleles will always be masked by dominant alleles.

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Theory of Evolution

“ Survival of the fittest”

Charles Darwin, On the Origin of Species (1859)?

Theory of Evolution

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● Evolution is change in the heritable characteristics of biological populations over successive generations.

● In evolution, fitness simply means reproductive success and reflects how well an organism is adapted to its environment.

● All life on Earth shares a common ancestor.

“Survival of the successful reproducers ”

“ Survival of the fittest”

Herbert Spencer, Principles of Biology (1864)

wikimedia

http://www.macleans.ca/wp-content/uploads/2013/02/5519745603_e6be133cf8.jpg

The selfish gene (The Immortal Gene)

● Richard Dawkins,1966

● Gene centered view of Evolution

○ Evolution occurs through the

differential survival of competing

genes, increasing the allele frequency of those alleles whose phenotypic trait effects successfully promote their own propagation.

wikipedia

Numbers of genes

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(M. Lynch, The Origins of Genome Architecture)

Organism # of protein coding genes

# of genes by prediction

HIV 9 10 viruses

Influenze A virus 11 14

Bacteriophage 66 49

Buchnera sp. 610 640 prokaryotes

T. maritima 1900 1900

E. coli 4300 4600

S. cerevisiae 6600 12000 eukaryotes

C. elegans 20000 100000

D. melanogaster 14000 140000

M. musculus 20000 2800000

Chromosome theory (1902)

“Chromosomes are the

carriers of genetic material (genes).”

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Walter Sutton (left) Theodor Boveri (right) Sister chromatids

1. Chromatid

2. Centromere

3. Short (p) arm

4. Long (q) arm

Chromosome structure

Junk DNAs (1)

● Susumu Ohno (大野乾)

● Noncoding region of the genome.

● Any DNA sequence that does not play a functional

role in development, physiology, or some other

organism-level capacity

L: https://www.nap.edu/read/10470/chapter/14 13

R: http://www.imm.ox.ac.uk/_asset/image/junkdna.jpeg

Junk DNAs (2)

● ENCODE Project

● Goal:

○ Mapping and characterizing the functionality of the entire human genome.

“ These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well studied protein-coding

regions. ”

The ENCODE Project Consortium

2012, Nature

“ … We examine several lines of evidence that support the notion that a substantial percentage of the DNA in many eukaryotic genomes lacks an organism-level

function and that the junk DNA concept remains viable post-ENCODE.”

Alexander F. Palazzo , T. Ryan Gregory 2014, PLOS Genetic

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Junk DNAs (3)

Genome

Genes and gene related sequence

Intergenetic DNA

Related sequences

Protein coding sequence

Transposable elements

Tandem repeats

Pseudogene

Introns, UTRs

Retrotransposons (LTRs, LINEs, SINEs)

DNA transposons

Microsatellites Minisatellites

Genome structure (1)

Genome: The genetic material of an organism.

Genome structure (2)

(T. Ryan Gregory, Nature Reviews Genetics, 2005)

Genome

Genes and gene related sequence

Intergenetic DNA

Related sequences

Protein coding sequence

Transposable elements

Tandem repeats

Pseudogene

Introns, UTRs

Retrotransposons (LTRs, LINEs, SINEs)

DNA transposons

Microsatellites Minisatellites

Genome structure (1)

Genome: The genetic material of an organism.

Tandem repeats (TRs, Simple sequence repeat)

● Microsatellites (1-10nt)

● Minisatellites (> 10nt)

● Repeat 5 - 50 times

● 50,000-100,000 dinucleotide microstaellites in human genome

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Tandem repeats (TRs)

● Mutation rate

○ 10

^-2

^-6

○ points mutation (10

^-10

^-11

○ (10

^-6

⁹

³

● Telomeres

○ TTAGGG 2,500 times in human

○ 11 kilobases at birth → 4 kilobases in old age

● Huntington’s disease

○ Expansion of CAG in gene coding region of Huntingtin protein

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Genome

Genes and gene related sequence

Intergenetic DNA

Related sequences

Protein coding sequence

Transposable elements (TEs)

Tandem repeats

Pseudogene

Introns, UTRs

Retrotransposons (LTRs, LINEs, SINEs)

DNA transposons

Microsatellites Minisatellites

Genome structure (1)

Genome: The genetic material of an organism.

(T. Ryan Gregory, Nature Reviews Genetics, 2005)

Transposable Elements (TE, transposons) (1)

● Barbara McClintock (1902 - 1992)

● First discovered in Maize (1948)

● 1983 Nobel Prize

● A DNA sequence that can change its position within a genome.

Transposable Elements (TE, transposons) (2)

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● Retrotransposons

○ copy and paste

○ LTRs, LINEs, SINEs

○ Retroviruses

● DNA transposons

○ cut-and-paste

○ Transposase

http://cubocube.com/dashboard.php?a=1182&b=1264&c=103

Horizontal Transmission of TEs (1)

● Mariner-like element

Proliferation

(Increase in copy number)

Spread in population

Stochastic loss Active elements

specie 1

specie 2 specie 2 specie3

Horizontal Transmission of TEs (2)

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“The consumption of food with associated environmental bacteria is the most likely mechanism that promoted this CAZyme update into the human gut microbe.”

Hehemann

Transfer of carbohydrate active enzymes from marine bacteria to Japanese gut

microbita

Hehemann, Nature, 2010

(Hehemann, Nature, 2010)

Crossing over

A B C

A B C

A B|B C

A B|B C

Unequal crossing over

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A B

B

C

A B

B

C

A B

B

C

A B

B

C

Chromosome translocation

Karyotype of Normal Cell

Karyotype of Cancer Cell

The structure of a eukaryotic protein-coding gene

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UTR: UnTranslated Regions ORF: Open Reading Frame

Post-transcriptional modification

Post-translational modification

Which is bigger, mRNA or the protein it codes for?

I

II

Which is bigger, mRNA or the protein it codes for?

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Cell division

● mitosis

● meiosis

Sister chromosome and homologous chromosome

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http://ib.bioninja.com.au/standard-level/topic-3-genetics/33-meiosis/sister-chromatids.html

Mitosis

https://en.wikipedia.org/wiki/Cell_cycle

Meiosis

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https://upload.wikimedia.org/wikipedia/commons/thumb/9/96/Meiosis_Overview_new.svg/1280px- Meiosis_Overview_new.svg.png

Meiosis

Gametogenesis

● spermatogenesis

● oogenesis

http://ib.bioninja.com.au/higher-level/topic-11-animal-physiology/114-sexual-reproduction/gametogenesis.html37

Centromere and Kinetochore

Spindle fibers

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https://en.wikipedia.org/wiki/Microtubule

Microtubule and tubulin

Assembly and Disassembly

https://www.mcb.ucdavis.edu/faculty-labs/al-bassam/research.html 41

Tyrosine and alpha-tubulin

TTL:tubulin-tyrosine ligase

Cortical side and egg side

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Strong centromere and week centromere

Chromosome Flipping -I

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Chromosome Flipping -II

Spindle asymmetry

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Conclusion

● Microtubule tyrosination promotes unstable interactions between selfish centromeres and the cortical side of the spindle.

● Spindle asymmetry drives non-Mendelian chromosome segregation

● Selfish centromeres have bigger chance to face toward

egg side,and pass their genetic information into next

generation.

Take home message

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● Selfish meiotic drivers exploit the asymmetry inherent in female meiosis to bias their

transmission.

Video link

https://www.youtube.com/watch?v=uNRBZ6ARQp4