Theme 4: DNA Muta/ons
14.1 The Rate and Nature of Muta3ons
• Most muta*ons are spontaneous and random
14.1.1 For individuals nucleo3des, muta3on is a rare event
◦ Highest rates of muta*on per nucleo*de per replica*on are found
among RNA viruses and retroviruses
• Perhaps because the backbone of an RNA strand is more
prone to spontaneous breakage than that of a DNA strand
• Perhaps because the replica*on of these genomes lacks a
proofreading func*on
◦ For other genomes, the rate of muta*on per nucleo*de per DNA
replica*on might simply reflect the limits of proofreading and
other repair mechanisms
• Certain nucleo*des are especially prone to muta*on and can exhibit
rates of muta*on that are greater than the average by a factor of 10 or
more
◦ Sites in the genome that are especially mutable are hotspots
• In some mul*cellular organisms, the rates of muta*on differ between
the sexes
◦ Example: In humans, rate of muta*on is greater in males than
females
• Rates for the mul*cellular animals depend on the type of cell:
◦ Rate of muta*on per nucleo*de per replica*on is greater in
soma3c cells than in germ-line cells (the reproduc*ve cells and
the cells that give rise to them)
14.1.2 Across the genome as a whole, muta3on is common
• For a par*cular cell, the overall muta*on rate depends on the number of
*mes DNA replica*on occurs and the size of the genome
◦ Takes into account the number of germ-line cell divisions and
genome size
, ◦ For DNA viruses, bacteria, and fungi (the bread mold), the average
number of new muta*ons per genome per genera*on is ~ 0.003
• So, in bacteria and fungi, roughly one cell division in every
eight yields a daughter cell with a new muta*on somewhere
in the genome
◦ For RNA viruses and retroviruses, the average number of new
muta*ons per genome reflects the high rate of muta*on per
nucleo*de
◦ Among mul*cellular animals, the average number of new
muta*ons per genome reflects the effects of mul*ple germ-line
cell divisions per genera*on of organisms as well as larger genome
size
• Such a large number of new muta*ons as occurs in the human genome
would be intolerable in organisms with a high density of protein-coding
genes
◦ Tolerable in humans because a mere 2.5% of genome codes for
protein
14.1.3 Only germ-line muta3ons are transmiEed to progeny
• Germ-Line Muta*ons: Muta*ons that occurs in eggs and sperm and the
cells that give rise to these reproduc*ve cells
◦ The rate of muta*on per organismal genera*on ma[ers more
than the rate of muta*on per cycle of DNA replica*on
• Soma*c Muta*ons: Muta*ons that occur in non-reproduc*ve cells
◦ The rate of muta*on per cycle of DNA replica*on ma[ers more
◦ These muta*ons are transmi[ed to progeny cells in mito*c cell
divisions (BUT, not to future genera*ons)
• Most cancers result from muta*ons in soma*c cells
◦ The muta*on may increase the ac*vity of a gene that promotes
cell growth and division, while in other cases, it decreases the
ac*vity of a gene that restrains cell growth and division
◦ BUT, a single soma*c muta*on isn't usually enough to cause
cancer
• ~2-3 muta*ons in different genes are needed
14.1 The Rate and Nature of Muta3ons
• Most muta*ons are spontaneous and random
14.1.1 For individuals nucleo3des, muta3on is a rare event
◦ Highest rates of muta*on per nucleo*de per replica*on are found
among RNA viruses and retroviruses
• Perhaps because the backbone of an RNA strand is more
prone to spontaneous breakage than that of a DNA strand
• Perhaps because the replica*on of these genomes lacks a
proofreading func*on
◦ For other genomes, the rate of muta*on per nucleo*de per DNA
replica*on might simply reflect the limits of proofreading and
other repair mechanisms
• Certain nucleo*des are especially prone to muta*on and can exhibit
rates of muta*on that are greater than the average by a factor of 10 or
more
◦ Sites in the genome that are especially mutable are hotspots
• In some mul*cellular organisms, the rates of muta*on differ between
the sexes
◦ Example: In humans, rate of muta*on is greater in males than
females
• Rates for the mul*cellular animals depend on the type of cell:
◦ Rate of muta*on per nucleo*de per replica*on is greater in
soma3c cells than in germ-line cells (the reproduc*ve cells and
the cells that give rise to them)
14.1.2 Across the genome as a whole, muta3on is common
• For a par*cular cell, the overall muta*on rate depends on the number of
*mes DNA replica*on occurs and the size of the genome
◦ Takes into account the number of germ-line cell divisions and
genome size
, ◦ For DNA viruses, bacteria, and fungi (the bread mold), the average
number of new muta*ons per genome per genera*on is ~ 0.003
• So, in bacteria and fungi, roughly one cell division in every
eight yields a daughter cell with a new muta*on somewhere
in the genome
◦ For RNA viruses and retroviruses, the average number of new
muta*ons per genome reflects the high rate of muta*on per
nucleo*de
◦ Among mul*cellular animals, the average number of new
muta*ons per genome reflects the effects of mul*ple germ-line
cell divisions per genera*on of organisms as well as larger genome
size
• Such a large number of new muta*ons as occurs in the human genome
would be intolerable in organisms with a high density of protein-coding
genes
◦ Tolerable in humans because a mere 2.5% of genome codes for
protein
14.1.3 Only germ-line muta3ons are transmiEed to progeny
• Germ-Line Muta*ons: Muta*ons that occurs in eggs and sperm and the
cells that give rise to these reproduc*ve cells
◦ The rate of muta*on per organismal genera*on ma[ers more
than the rate of muta*on per cycle of DNA replica*on
• Soma*c Muta*ons: Muta*ons that occur in non-reproduc*ve cells
◦ The rate of muta*on per cycle of DNA replica*on ma[ers more
◦ These muta*ons are transmi[ed to progeny cells in mito*c cell
divisions (BUT, not to future genera*ons)
• Most cancers result from muta*ons in soma*c cells
◦ The muta*on may increase the ac*vity of a gene that promotes
cell growth and division, while in other cases, it decreases the
ac*vity of a gene that restrains cell growth and division
◦ BUT, a single soma*c muta*on isn't usually enough to cause
cancer
• ~2-3 muta*ons in different genes are needed
