Chapter 4.  Mutation and Genetic Variation

• "Mutations are the raw material of evolution"
• Mutation = any change in genetic material which is passed on to succeeding generations.
• Mutations vary greatly in scale and impact (Table 4.1).
• New mutations must be in germline to be transmitted to offspring (note difference between animals and plants in this regard).
• DNA, genes, alleles and traits.  Are there genes "for" eye color, big beaks, deep roots, etc.?  This language is shorthand for the genetic control of development.
• Small changes in gene expression and timing of expression can have big effects on development (examples - twining vines, webbed feet).
• Point mutations - the most frequent type, result from uncorrected mistakes during DNA replication.
• Consequence - new allele of an existing gene is formed.
• Depending on position of nucleotide substitution, a new gene product (polypeptide) may be formed with a different amino acid inserted.
• If new polypeptide is formed, it may function identically or quite differently, depending on position and chemistry of new amino acid.
• New polypeptide may be better than the old polypeptide or (more likely) worse than the old polypeptide.
• "Better" or "worse" depends on the environment.  Clear example of this is the sickle cell mutation in the gene encoding hemoglobin.
• (Point) Mutation rates - how often are new alleles formed?  (See Table 4.1).  As a rule of thumb, mutation rates are about:
• 1/10,000,000 per nucleotide (this is the DNA polymerase error rate)
• 2-3/1000 cells of unicellular organisms carry a detectable mutation.
• Caenorhabditis elegans - about 15 new mutations per individual per generation.
• Homo sapiens - about 1.6 new alleles per individual per generation.
• There are many issues associated with determining mutation rates:
• Not all nucleotide substitutions result in amino acid substitutions (e.g., silent site mutations).
• Not all amino acid substitutions affect protein function.
• Mutation rates vary among individuals within populations.
• Mutation rates vary among species, especially those with different life spans.
• Mutation rates vary among genes - coding regions repaired more carefully than non-coding regions.
• Fitness effects of mutations
• In terms of frequency: neutral > deleterious > beneficial.
• Is mutation rate subject to natural selection?  Work by de Visser et al suggests "maybe."
• Origin of new genes
• Unequal crossing over can result in gene duplication (Fig. 4.7).  Some duplicate genes are free to evolve new functions, other may degenerate into pseudogenes.
• Overprinting (overlapping genes) - mRNA transcript has several reading frames, each with its own start point, thus multiple proteins can be produced from a single gene.
• Reverse transcription of of mRNA, insertion of cDNA into genome.  This can result in a new copy of the gene in a different chromosome.
• "New genes" vs. "new alleles" - be clear about the distinction.
• Inversions - chromosomes break, are repaired with a segment inserted backwards (Fig. 4.10).  This will prevent crossing over during meiosis and genes in inverted segment will be linked, i.e., inherited as a unit ("supergene").
• Polyploidy - duplication of entire chromosome sets: diploids become tetraploid, octoploid, etc.
• Mechanism - mistakes during meiosis (animals and plants) or germline mitosis (in plants)
• As chromosomes are duplicated, so are genes.  This provides opportunity for new gene functions to develop.
• Since individuals with different chromosome numbers are not interfertile, new species can arise overnight.
• Measuring genetic diversity in populations
• This is usually done indirectly be measuring protein diversity electrophoretically.  Recently, direct DNA techniques have become more common (e.g. PCR techniques).
• Gene (allele) frequencies are calculated (see example on pp.129-131 using Delta 32 allele).
• Populations tend to be polymorphic for many loci and have many alleles per locus - This ...
• Is "genetic diversity".
• Is a consequence of past mutations.
• Provides raw material for evolution by natural selection.
• Can be explained in two ways:
• "Selectionist theory".  Natural selection acts
• against homozygotes
• shifts in time and space
•  "Neutral theory":  most of the alleles are selectively equivalent.