Molecular Anthropology and Population Genetics Review

Comprehensive flashcards covering molecular anthropology, population genetics, ancient DNA, human evolution, and genetic sequencing technologies based on the lecture notes.

Transitions

A type of single-base change mutation where a purine replaces a purine or a pyrimidine replaces a pyrimidine; these are more common than transversions.

CpG sites

Genomic regions that mutate frequently because methylated Cytosine ($C$) spontaneously deaminates to Thymine ($T$).

Replication slippage

A mutational mechanism responsible for indels (short insertions/deletions) and high mutation rates in STRs/VNTRs.

Structural variants (SVs)

Genetic variants greater than $50\,bp$ (including deletions, duplications, and inversions) that are often caused by non-allelic homologous recombination (NAHR) and require long reads for detection.

Sanger sequencing

A methodology developed in 1977 using PCR and ddNTPs (missing a 3' OH) to randomly terminate chains, allowing fragments to be read by size or colour; reliable but low throughput.

Illumina (NGS)

A sequencing technology using short reads ($75-500\,bp$) and sequencing-by-synthesis with reversible terminators on a flow cell; struggles to resolve repeats occupying $>15\%$ of the genome.

PacBio (SMRT)

A sequencing technology using zero-mode waveguides (ZMW) where fluorescent nucleotides are detected in real time by a fixed polymerase to produce HiFi consensus reads.

Oxford Nanopore (ONT)

A technology that threads single-stranded DNA through a nanopore and decodes changes in ionic current using machine learning to produce ultra-long reads (up to $~1\,Mb$).

ATAC-seq

A functional assay using $Tn5$ transposase to insert adapters into open chromatin to map accessible or active genomic regions.

Hi-C

A sequencing-based assay that maps 3D genome interactions to reveal topologically associating domains (TADs).

ChIP-seq

An assay that uses specific antibodies to immunoprecipitate protein-DNA complexes, showing the location of transcription factors or histone modifications.

Q-score formula

A statistical quality score defined as $Q = -10 \cdot \log_{10}(p)$, where $p$ is the probability that the base call is incorrect.

k-mer hashing

An indexing method used in read mapping to quickly find candidate positions, as a single mismatch invalidates $k$ k-mers at once.

Pangenome graphs

A non-linear genomic representation that replaces the single linear reference genome with a graph reflecting the diversity of many individuals or populations.

Wright-Fisher (WF) Model

An idealized population model characterized by random mating, non-overlapping generations, constant population size, unrelated individuals, and no selection.

Effective population size ($N_e$)

The size of an idealized Wright-Fisher population that would produce the observed gene pool; for humans, $N_e \approx 20,000-25,000$.

Genetic drift

Random fluctuations of allele frequencies due to random sampling between generations, which destroys diversity over time and is more impactful in small populations.

Extinction vortex

A phenomenon in small populations where drift increases homozygosity and exposes harmful recessive mutations, reducing fitness and increasing extinction risk.

Balancing selection (overdominance)

A type of selection where heterozygotes are fitter than homozygotes, maintaining both alleles at equilibrium ($\approx 50\%$); exemplified by the MHC region.

Extended Haplotype Homozygosity (EHH)

A tool to detect recent selective sweeps by identifying long, identical haplotype segments shared among individuals around a selected site.

$$F_{ST}$$

A measure of allele frequency differences used to detect selection between populations on an intermediate timescale.

FOXP2

A transcription factor linked to speech that shows 2 amino acid changes between humans and chimpanzees in just $6\,Ma$, serving as a signal of positive selection.

Neutral allele fixation probability

A new neutral mutation has a probability of fixation equal to $1/N_e$; an existing neutral allele has a probability equal to its current frequency ($p$).

Neutral fixation time

Under neutrality, it takes an average of $2N_e$ generations for an allele to reach fixation.

$|N_e \cdot s|$ criterion

A quantitative rule where selection is effective if $|N_e \cdot s| \gg 1$; if $|N_e \cdot s| \ll 1$, genetic drift dominates the fate of the allele.

Mitochondrial Eve

The most recent common maternal ancestor of all humans, estimated to have lived $~150,000-200,000$ years ago, rooted in Africa.

Introgression

The transfer of genetic material from one population or species (e.g., Neanderthals or Denisovans) to another (modern humans) through admixture.

Ramapithecus

A fossil ape once misidentified as a deep bipedal human ancestor but later revealed to be the female form of Sivapithecus, an orangutan ancestor.

Incomplete Lineage Sorting (ILS)

A phenomenon where the genealogy of a gene does not match the species tree because ancestral polymorphisms were not fully sorted before lineage splits.

GWAS significance threshold

The strict statistical cutoff of $p < 5 \times 10^{-8}$ used in Genome-Wide Association Studies to correct for massive multiple testing.

EPAS1

A Denisovan-derived gene segment found at high frequency in Tibetans that facilitates adaptation to high-altitude hypoxia.

TBX15/WARS

A Denisovan-derived segment present in Greenlandic Inuit at nearly $100\%$ frequency, associated with cold adaptation and facial morphology.

KIF18A and KNL1

Cell cycle genes where modern human versions contribute to chromosome segregation fidelity and a longer metaphase compared to ancestral versions.

Human Accelerated Regions (HARs)

Sequences conserved across mammals that show an unusually high mutation rate in the human lineage, indicating positive selection on regulatory functions.

hCONDELs

Conserved genomic sequences in other species that have been completely deleted in humans, potentially removing tissue-specific gene expression.

SVA elements

A type of transposable element restricted to great apes that can carry transcription-factor binding sites when inserting into the genome.

Base editing

A CRISPR-derived method using Cas9 nickase and cytidine deaminase to convert $C \rightarrow U$ (read as $T$) without causing double-strand breaks.

AHR (Aryl hydrocarbon receptor)

A transcription factor where the modern human version is less sensitive to toxins from smoke and charred food compared to the ancestral version.

aDNA fragmentation

A characteristic of ancient DNA where molecules are very short, often peaking at $~35\,bp$ in $40,000$-year-old samples.

Deamination damage

A chemical degradation in aDNA involving $C \rightarrow U$ conversion, resulting in a characteristic $C \rightarrow T$ mismatch pattern at the 5' end.

ABBA-BABA test (D-statistic)

A genetic test comparing an outgroup and three core populations to detect excess shared derived alleles, used to identify Neanderthal introgression in non-Africans.

Reproductive Conflict Hypothesis

A model explaining menopause where inclusive fitness favors older females helping relatives (sons/grandsons) rather than competing for resources to reproduce.

Tooth pulp chamber

The standard sampling site for ancient pathogen screening because it is highly vascularized and likely to contain blood-borne pathogen traces.

Yersinia pestis pla gene

The gene for systemic infection capacity that, according to prehistoric genomes, evolved earlier than flea-borne transmission adaptation.

Entangled Bank Model

A model of Pacific peopling describing a rapid initial dispersal followed by significant waves of local admixture with Papuan populations.

Isolation by distance

A pattern where genetic similarity between populations decreases as the geographic distance between them increases.

Avar patrilocality

A social structure identified through pedigrees where adult males remained in their birth communities while adult females moved between different site clusters.

Levirate

A social custom where a widow marries a close male relative (e.g., a brother) of her deceased husband, identified in Avar genetic pedigrees.

Turboslavism

A pseudo-historical narrative that makes exaggerated nationalist claims about ancient Slavic empires using manipulated genetic and historical maps.

Vitamin D hypothesis

The theory that selection for light skin in northern agricultural populations occurred to allow sufficient UV penetration for vitamin D synthesis as diets became meat-poor.

Gulf Stream

A warm ocean current that makes agriculture possible in Scandinavia, indirectly creating the selective pressure for very light skin in that region.