LIFESCI 7B Lecture Notes - Lecture 1: Germline Mutation, Mutation, Somatic Cell
10 Jun 2018
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14.1 The Rate and Nature of Mutations
● Most mutations are spontaneous and random, it’s benefit towards the organism based on chance
○ Mutations arise randomly and independent of other mutations in the cell.
For individual nucleotides, mutation is a rare event.
● RNA mutates more than DNA as it is more unstable and lacks a proofreading function
● hotspot A site in the genome that is especially mutable
○ Can exibit mutation rates up to 10x the average rate of 1/10^10 per nucleotide per replication
● Rates in mutation can differ between sexes in some multicellular organisms
○ For humans, more mutations in males than females
■ Males’ cells go through more divisions before meiosis than females
■ For males, # of mutations increases w/ age; for women the # stays relatively constant
● Distinction in mutations that happen in germ (reproductive) cells vs. somatic cells
○ Mutation rate higher in somatic than germ cells for humans
Across the genome as a whole, mutation is common.
● while humans have the smallest rate of mutation per nucleotide per replication, they also have the
largest rate of mutation per genome per generation
○ Effects often neutral because of our high percentage of non protein coding genes
○ number of new mutations in organisms following a round of genome replication generally
increases with larger genomes
Only germ-line mutations are transmitted to progeny.
● germ-line mutation A mutation that occurs in eggs and sperm or in the cells that give rise to these
reproductive cells and therefore is passed on to the next generation.
○ Hereditary, transmitted to future generations
○ rate of mutation per genome per generation matters more
○ Important in evolutionary process
● somatic mutation A mutation that occurs in somatic cells.
○ Non-hereditary, Affect only the individuals, are not passed on to future generations; mutations
just passed to daughter cells within the body
○ rate of mutation per nucleotide per replication matters more
○ Cancers result from mutated somatic cells, in either protooncogenes or tumor supressor
proteins
■ Multiple somatic mutations needed to cause cancer
● from a series of mutations that arise in the descendants of a single somatic cell
(single cell lineage)
● To cause cancer, the mutations must occur sequentially in a single cell line
What can your personal genome tell you about your genetic risk factors?
● genetic risk factor Any mutation that increases the risk of a given disease in an individual.
○ Does not cause disease, but makes it more likely to occur
● The DNA sequence of each of our personal genomes can reveal the genetic risk factors that each of us
carries for a number of diseases
○ There’s also environmental risk, like ifestyle choices (ex: smoking tobacco, sun exposure,
unhealthy diet, etc)
Mutations are random with regard to an organism’s needs.
● Role of environment is not to create specific mutations, but instead to select for them
○ Certain circumstances/environments do not TRIGGER mutations, as seen in the bacteria repica
plating experiment
15.1 Genotype and Phenotype
● Mutations result from genetic variation; can be harmful, neutral, or beneficial
○ When favorable, allows organisms to evolve and become adapted to environment over time
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Genotype is the genetic makeup of a cell or organism; phenotype is its observed characteristics.
● genotype The genetic makeup of a cell or organism; the particular combination of alleles present in an
individual.
○ Variation of genotypes of a population depend on its gene pool
● polymorphism Any genetic difference among individuals sufficiently common that it is likely to be
present in a group of 50 randomly chosen individuals (e.g. eye color).
○ Result of mutation; at one point every individual had same genotype
○ Ex: many have C-G where others have A-T
● phenotype The expression of a physical, behavioral, or biochemical trait; an individual’s observable
phenotypes include height, weight, eye color, and so forth.
○ Result of genotype and environment
The effect of a genotype often depends on several factors.
● alleles The different forms of a gene, corresponding to different DNA sequences (polymorphisms) in
each different form. (gene: hair color: different alleles: brown vs. blonde)
○ homozygous Describes an individual who inherits an allele of the same type from each parent,
or a genotype in which both alleles for a given gene are of the same type.
○ heterozygous Describes an individual who inherits different types of alleles from the parents, or
genotypes in which the two alleles for a given gene are different
● Harmfulness or benefits of sickle cell anemia S allele show us
○ It depends on homozygous/hteterozygous inheritance
○ Effect of a genome depends on the environment (homozygous/heterozygous doesn’t
automatically correspond to beneficial harmful)
Some genetic differences are major risk factors for disease.
● Mutations and polymorphisms can be risk factors for diseases like emphysema, making it more likely for an
individual
○ Esp. when combined w/ environmental factors like smoking tobacco
● genotype-by-environment interaction Unequal effects of the environment on different genotypes, resulting
in different phenotypes. Combo of certain environment and certain gene can be especially bad (or good)!
○ Genetic and environmental factors combine to influence phenotype, combo of the two risk factors is
worse than either of their individual effects
Not all genetic differences are harmful.
● Most genetic differences are neutral, because of the large portion of noncoding genes in the human genome
and just mutations that don’t really affect survivability/reproductivity
○ Ex: The taster/nontaster polymorphism
A few genetic differences are beneficial.
● in human populations, beneficial mutations are often discovered through their effects in protecting against
infectious disease
○ Ex: sickle-cell gene that protects against malaria, or another that protects against HIV/AIDS
○ Other beneficial mutations can allow organisms to better adapt to their environment
16.1 Early Theories of Inheritance
Early theories of heredity predicted the transmission of acquired characteristics.
● Hippocrates theorized that each part of the body of a mature male collected in a reproductive organ that
determined inherited traits (charactristics) of offspring
○ Believed traits acquired during lifetime could be passed to offspring
● Aristotle concluded that the process of heredity transmits only the potential for producing traits present in the
parents, and not the traits themselves
Belief in blending inheritance discouraged studies of hereditary transmission.
● blending inheritance Darwin’s now-discredited model in which heredity factors transmitted by the parents
become intermingled in the offspring instead of retaining their individual genetic identities.
○ Black bunny+white bunny=grey bunny
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Most mutations are spontaneous and random, it"s benefit towards the organism based on chance. Mutations arise randomly and independent of other mutations in the cell. For individual nucleotides, mutation is a rare event. Rna mutates more than dna as it is more unstable and lacks a proofreading function. Hotspot a site in the genome that is especially mutable. Can exibit mutation rates up to 10x the average rate of 1/10^10 per nucleotide per replication. Rates in mutation can differ between sexes in some multicellular organisms. For humans, more mutations in males than females. Males" cells go through more divisions before meiosis than females. For males, # of mutations increases w/ age; for women the # stays relatively constant. Distinction in mutations that happen in germ (reproductive) cells vs. somatic cells. Mutation rate higher in somatic than germ cells for humans. Across the genome as a whole, mutation is common.
