MUTATIONMUTATION

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►only those adapted to their environment will

survive

►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 generations

Mutations Can Be: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 mutation

► 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 replication.

►mutagensmutagens physicalphysical

►ex. X-rays, UVex. X-rays, UV

chemicalchemical►ex. nitrites, gasoline fumes, cigarette smokeex. nitrites, gasoline fumes, cigarette smoke

Types of MutationsTypes of Mutations1. single-gene mutations

changes in nucleotide sequence of one gene

a) point mutation (mispairing) most frequent type single base pair is substituted/inserted/deleted

b) frameshift mutation (strand slippage) change of reading frame a HUGE deal!

►effect can be minor, or not…

depends on final consequence

(reading the code)

Silent

Neutral

Nonsense

Missense

i) silent mutation

►aa sequence stays the same

ii. missense mutation

►alters aa sequence of a protein

Single base change in hemoglobin gene causes sickle cell anemia

wildtypeallele

mutantallele

wildtypephenotype

mutantphenotype

iii. nonsense mutation

►mutation that inserts a “stop” earlier than it was

iv. frame-shift mutation

►reading frame shifts

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

Types of MutationsTypes of Mutations

2. 2. chromosome mutations changes in chromosomes, can involve

many genes

usually a consequence of cross-over gone wrong (meiosis)

So…if this is dangerous, how do So…if this is dangerous, how do you fix it?you fix it?

ERROR CORRECTIONERROR CORRECTION

► a human cell can copy its DNA in a a human cell can copy its DNA in a few hoursfew hours

if you were to type this, 1 letter per if you were to type this, 1 letter per second, it would take you close to 100 second, it would take you close to 100 yearsyears

200 books at 1000 pages each…200 books at 1000 pages each…

►error rate: 1/1 billion pairs (3 billion pairs total)

MECHANISMS OF REPAIRMECHANISMS OF REPAIR

1. 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 incorrect base is taken out, correct

added

2. Mismatch repair- similar in prokaryotes and eukaryotes- protein group replaces mismatched

nucleotide with correct one

Mutations and EvolutionMutations 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!

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.Numbers represent thousand years before present, with 2-4% mutation rate per 1 million years.

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

lineage. The loss of that particular gene may have caused the thinning of human body hair. The gene loss occurred relatively recently in human evolution—less than 240,000 years ago.

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.

The period that followed was marked by a strong increase in cranial capacity, promoting speculation that the loss of the gene may have removed an evolutionary constraint on brain size in the genus Homo.

►Compared with

chimps, humans have evolved weak jaw muscles and jaw bones – cooked food and your brain?

►The expansion of the human brain may have involved a snowball effect, in which initial mutations caused further mutations that enhanced the brain even more

►Humans' big brains require extra energy – three mutations may have helped meet that demand

► In 6 million years, our diet gradually changed from fruit and leaves to starchy grains. Genes involved in digestion offer a timeline to those dietary changes

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 compared with human and Neanderthal FOXP2

►You can teach a chimp tricks, but it won't ever talk. The human "language gene" has helped us learn the rules of speech and maybe even grammar