Genetics and Fitness — Lecture Notes (Identity, Mutation, and Selection)

Foundations: Mutation Types and Key Terms

• Mutations can affect:

  • DNA structure

  • DNA function

  • The encoded protein

  • Overall fitness

• Common mutation types discussed:

  • Point mutation: single nucleotide change (e.g., thymine to cytosine at a given position)

  • SNP: Single Nucleotide Polymorphism

  • Definition: ext{SNP} = ext{Single Nucleotide Polymorphism}

  • Insertion: addition of nucleotides

  • Deletion: removal of nucleotides

  • Indel: insertion/deletion polymorphism (mutations that insert or delete bases)

  • Frameshift: caused by insertions/deletions that shift the reading frame, especially harmful if in a coding region

• Large-scale mutations (chromosomal):

  • Deletion (loss of a section)

  • Duplication (gain of a section)

  • Inversion (section flips orientation between two copies)

  • Translocation (a piece of one chromosome attaches to another)

• Chromosomal architecture terms:

  • Exon: coding portions of a gene

  • Intron: non-coding portions interspersed between exons

  • Gene: basic unit of heredity, often composed of multiple exons and introns

  • Genome: all genetic material in an organism

  • Locus: a chromosomal location of a gene or a region

  • Promoter/Regulatory elements: regions that control gene expression

  • Centromere: chromosome center

  • Telomere: chromosome ends

• Example visualization note:

  • Inversions can involve exons (e.g., exons 1–22) and can disrupt coding sequences, potentially altering protein function (e.g., a gene involved in blood coagulation)

• Practical takeaway:

  • Mutations are not uniformly distributed in effect; some are neutral, deleterious, or adaptive, with varying impacts on fitness depending on environment and life stage

Types of Mutations and Their Functional Consequences

• Loss of function mutations:

  • Often recessive because a single functional copy can rescue function

  • Example in Drosophila (eye color gene): loss of function mutations are typically recessive

  • Dominance can vary by population; not universal across species or contexts

• Gain of function mutations:

  • Can create new or enhanced activity (e.g., altered developmental traits in model organisms like Drosophila or butterflies)

• Lethal mutations:

  • Mutations that cause death before or during development; individuals carrying such mutations may not survive to reproductive age

• Functional outcomes are often categorized as:

  • Deleterious: reduces fitness

  • Adaptive: increases fitness in a given environment

  • Neutral: no substantial effect on fitness

• Fitness framework (ecological view):

  • Fitness is primarily tied to survivorship and reproductive success

  • Late-onset diseases (e.g., adult-onset cancers) often have limited immediate impact on fitness because reproduction typically occurs earlier

• Illustrative questions addressed:

  • Why are late-onset diseases sometimes considered to have limited impact on fitness?

  • How do grandmother effects and cultural differences influence evolutionary considerations of fitness in humans?

The Distribution of Mutation Effects on Fitness

• Core claim about the fitness effects of new mutations:

  • Most new mutations are deleterious and reduce fitness; many cause early embryonic lethality, leading to miscarriages or non-viable conceptions

• Quantitative framing (conceptual):

  • A rough population-genetics estimate suggests that a substantial fraction of conceptions involve lethal mutations, contributing to a high miscarriage rate; a commonly cited figure is on the order of P( ext{miscarriage}) \approx 0.5 (about 50%) in the context of early, lethal mutations

• For mutations that do not kill outright, the next most common category is neutral mutations ( ext{no substantial effect on fitness})

  • Fitness distribution shape (conceptual histogram):

  • Lethal mutations: left tail (very low fitness)

  • Deleterious mutations: somewhat left tail

  • Neutral mutations: peak near zero effect on fitness

  • Adaptive mutations: rare, at the far right tail

• Implication:

  • Among all genetic differences in a population, only a small fraction are expected to have substantial adaptive effects; many differences are neutral or mildly deleterious

• Fitness as a function of reproduction and survival:

  • W \propto S \,\times\, R where W is fitness, S is survivorship, and R is reproductive success

• Student question context:

  • If a late-onset condition (e.g., breast cancer gene risk) does not affect reproduction, does it affect fitness?

  • Answer: generally not majorly in terms of inheritance unless it impacts survivorship before/during reproduction; late-onset effects can have secondary ecological and demographic consequences but are often less directly selected against because they occur after reproductive age

Adaptive Mutations and Gene–Environment Interactions

• Adaptive mutations are relatively rare compared to the total number of mutations in a genome

  • The majority of genetic differences among individuals are not strongly adaptive

• Balance (heterozygote advantage) selection as a special case:

  • Example discussed: sickle cell trait provides protection against malaria in heterozygotes in certain environments

  • This is a classic case of an adaptive mutation that is advantageous only in a specific environment, illustrating gene–environment interaction

  • General equation framing: a gene–environment interaction can tilt whether a variant is advantageous or not, depending on the ecological context

• Gene × environment interactions:

  • Concept: the effect of a genetic variant depends on environmental conditions, not just the sequence itself

  • Expect to study these interactions more in subsequent lectures and lab work

• Practical guidance for interpretation:

  • Most mutations will not have a large adaptive advantage in a broad sense; when they do, the environment can determine whether that advantage translates into higher frequency in the population

• Open research context:

  • Identifying adaptive mutations is an active area; large population-genomics datasets and nonmodel systems are used because humans cannot be ethically or practically manipulated for experiments

Key Genetic Terminology to Know (Foundational Definitions)

• Gene: the basic unit of heredity; the functional unit that can include coding sequences and regulatory elements

• Genome: the complete set of genetic material in an organism

• Locus: a specific location on a chromosome where a gene or genetic marker sits

• Polymorphism: the presence of multiple alleles at a locus within a population

• SNP (Single Nucleotide Polymorphism): a single base-pair variation at a specific locus among individuals

  • ext{SNP} = ext{Single Nucleotide Polymorphism}

• Exon: a portion of a gene that codes for a portion of the final protein

• Intron: a noncoding segment within a gene that is removed during RNA processing

• Regulatory element: regions such as promoters and enhancers that control when, where, and how much a gene is expressed

• Dominant allele: an allele that can mask the effect of a recessive allele in a heterozygote

• Recessive allele: an allele whose effect is masked in a heterozygote

• Mutation: any heritable change in the DNA sequence

• Frameshift: a mutation that shifts the reading frame of a gene, typically due to insertions or deletions in coding regions

• Indel: insertion or deletion polymorphism

• Inversion: a chromosome segment is flipped, changing gene order and potentially gene function

• Translocation: a segment of one chromosome becomes attached to another chromosome

• Telomere: the protective end cap of a chromosome

• Centromere: the region of a chromosome that connects sister chromatids during cell division

• Loss of function mutation: mutation that reduces or abolishes the function of a gene product

• Gain of function mutation: mutation that leads to a new or enhanced activity of a gene product

• Lethal mutation: a mutation that causes death before reproduction

• Adaptive mutation: a mutation that increases fitness in a given environment

• Neutral mutation: a mutation that has no detectable effect on fitness

Real-World Relevance and Ethical Considerations

• The study of genetic variation informs understanding of disease susceptibility, cancer risk (e.g., BRCA1/BRCA2-related breast cancer risk), and population health

• Ethical implications include privacy around genetic identity, potential stigmatization, and the appropriate use of genetic information in education and policy

• The course emphasizes careful interpretation of genetic information, avoiding overgeneralizations about individuals based on group-level data

• Emphasis on the limitations of applying model organisms to human biology; foundational concepts are built in stages to understand complexity

Practical Takeaways for Exam Preparation

• Be fluent with core terms and acronyms:

  • ext{SNP}, ext{Indel}, ext{Frameshift}, ext{Exon}, ext{Inversion}, ext{Translocation}, ext{Promoter}, ext{Regulatory element}

• Understand the types of mutations and their typical effects on fitness and phenotype

• Distinguish between deleterious, neutral, and adaptive mutations and know how environment can shift adaptive value

• Remember the population-genetics perspective on fitness:

  • Fitness is tied to survivorship and reproduction

  • Late-onset diseases may not be strongly selected against if they occur after reproduction

• Recognize that dominance and recessivity can vary by population and context; there are few absolutes in complex human genetics

• Appreciate the link between genome structure and function (exons and coding regions) and how structural changes (inversions, translocations) can disrupt function

• Be prepared to discuss how researchers identify signatures of selection and adaptive regions in the genome across populations

Quick Recap of the Core Concepts

• Variation in humans derives from genetic and environmental sources, with natural selection acting on genetic variation to shape fitness and population structure

• Mutations come in many forms (SNPs, indels, large-scale chromosomal changes) with a spectrum of fitness effects, from lethal to neutral to adaptive

• The majority of new mutations are deleterious or lethal, contributing to miscarriages or nonviable pregnancies, while a smaller subset are neutral or adaptive

• Gene–environment interactions are crucial for understanding when a mutation is beneficial; heterozygote advantage (balance selection) is a key example

• Foundational genetic terms (gene, genome, locus, exon, promoter, etc.) provide the language for discussing the architecture and regulation of genomes

• Ethical and practical implications frame how we study and apply genetics in education, medicine, and society