MUTATION

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MUTATION

 a permanent change in the nucleotide sequence of a cell’s DNA

 can be passed on to daughter cells

 typically neutral or harmful, rarely beneficial

►allow species to change and adapt over time

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► Multicellular organisms have two types of

mutations:

 Somatic mutations

►passed on during mitosis, but not to subsequent generations

 _Germ-line_mutations

►occur in cells that give rise to gametes, passed to subsequent

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Mutations Can Be:

►

spontaneous

 take place naturally as a result of normal molecular interactions (ex. DNA pol made a mistake, 1/10–9)

►ex. DNA replication, transposons (jumping genes)

►

induced

 _{caused by agents outside the cell}

 _{mutagen: a substance that increases the rate of}

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► ex. nitrous acid (HNO₂)

 can turn C in DNA into U

► ex. benzpyrene, a component of cigarette smoke

 adds a large chemical group to G, making it unavailable for base pairing

► ex. ionizing radiation (X-rays)

 produces highly reactive chemical species called free radicals, which can change bases in DNA to unrecognizable (by DNA polymerase) forms

 It can also break the sugar–phosphate backbone of DNA, causing chromosomal abnormalities

 UV is absorbed by thymine in DNA, causing it to form interbase covalent bonds with adjacent nucleotides. This, too, plays havoc with DNA

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►

mutagens can be

 physical_physical

►ex. X-rays, UVex. X-rays, UV

 chemical_chemical

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Types of Mutations

1. single-gene mutations

 changes in nucleotide sequence of one gene

a)

point mutation (mispairing)

 most frequent type

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►

effect can be minor, or not…

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Silent Neutral

Nonsense

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i. silent mutation

►

aa sequence stays the

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ii. missense mutation

►

alters aa sequence

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Single base change in hemoglobin gene causes

sickle cell anemia

wildtype allele

mutant allele

wildtype

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iii. nonsense mutation

►

mutation that

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b)

frameshift mutation

(strand slippage)

 change of reading frame

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► Base substitutions (point mutations) ,insertions, and Base substitutions (point mutations) ,insertions, and

deletions

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Types of Mutations

2. 2. chromosome mutations

 _{changes in chromosomes, can involve many}

genes

 _{usually a consequence of cross-over gone}

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So…if this is dangerous, how do you

fix it?

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ERROR CORRECTION

►

a human cell can copy its DNA in a few

hours

 if you were to type this, 1 letter per second, it _{if you were to type this, 1 letter per second, it}

would take you close to 100 years

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►

error rate: 1/10

6

pairs or 1/10

9

pairs (3

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MECHANISMS OF REPAIR

1.

Proofreading

- DNA polymerase I and DNA polymerase II

- both proof-read and “fix” mistakes as new

DNA is being made

 99% of mistakes are caught this way

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2.

Mismatch repair

-

similar in prokaryotes and eukaryotes

-

protein group replaces mismatched

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Mutations and Evolution

►

typically neutral or harmful, rarely beneficial

►allow species to change and adapt over time

•

random accumulation of mutations (in the

extra copies of genes) can lead to the

production of new useful proteins and new

functions!...even NEW SPECIES!!!!

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How we know what happened

when

► 1. Radiometric dating relies on half-life decay of

radioactive elements to allow scientists to date rocks and materials directly.

► 2. Stratigraphy provides a sequence of events

from which relative dates can be extrapolated.

► 3. Molecular clocks allow scientists to use the

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Below are DNA sequences for the same gene in three different species. Based on these DNA sequences,

which is the most accurate cladogram to represent the relationship between species X, Y, and Z?

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How do we study this?

►

rocks (archeology)

►

bones (dating/homologies)

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► It is important to remember that:

1. Humans did not evolve from chimpanzees. Humans and chimpanzees are evolutionary cousins and share a recent common ancestor that was neither chimpanzee nor human.

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World map of human migrations, with the North Pole at center. Migration patterns are based on studies of mitochondrial (matrilinear) DNA. Dashed lines are hypothetical migrations.

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Our sense of smell sucks…

► 80 genes were lost in the human lineage after separation

from the last common ancestor with the chimpanzee. 36 of those were for olfactory receptors.

Our immune systems are amazing, allowing us to live in very large groups

► Genes involved in chemoreception and immune response

are overrepresented

We’re the “hairless ape”

► A gene for type I hair keratin was lost in the human

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Our jaws are not all that useful

► Stedman et al. (2004) stated that the loss of the

sarcomeric myosin gene MYH16 in the human lineage led to smaller jaw muscles.

► They estimated that the mutation that led to the

inactivation (a two base pair deletion) occurred 2.4 million years ago, predating the appearance of Homo

ergaster/erectus in Africa.

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► Compared with

chimps, humans have evolved weak jaw

muscles and jaw bones – cooked food and

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► The expansion of the

human brain may have involved a snowball

effect, in which initial mutations caused

further mutations that enhanced the brain

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► Humans' big brains

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► In 6 million years, our

diet gradually changed from fruit and leaves to starchy grains.

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We can TALK

► Humans and Neanderthals also share the FOXP2

gene variant associated with brain development and with speech in humans, indicating that

Neanderthals may have been able to speak.

► Chimps have two amino acid differences in FOXP2

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► You can teach a chimp

tricks, but it won't ever talk. The human

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