BIOL0003 Lecture 14: Sex with a Single Parent

Parhenogenesis and Species Case Studies

• Timema (Walking Sticks) Parthenogenesis: The transcript highlights several clades of Timema species, distinguishing between sexual and parthenogenetic (single-parent asexual) species. These species are approximately $20\,\text{mm}$ in size.     * Northern Clade:         * T. poppensis (Sexual)         * T. douglasi South (Parthenogenetic)     * Santa Barbara Clade:         * T. cristinae (Sexual)         * T. monikensis (Parthenogenetic)     * Southern Clade:         * T. podura (Sexual)         * T. genevievae (Parthenogenetic)         * T. bartmani (Sexual)         * T. tahoe (Parthenogenetic)         * T. boharti (Sexual)         * T. chumash (Parthenogenetic)     * Additional Species Linked to Clades:         * T. knulli         * T. petita         * T. californicum         * T. shepardi         * T. landelsensis         * T. sp "Cuesta ridge"
• Dolly the Sheep: Cited as an example of a single-parent mammal, created through somatic cell nuclear transfer.

The Biology and Structure of the Y Chromosome

• General Structure: The Y chromosome contains specific regions that determine male sex and facilitate minimal pairing with the X chromosome.     * Pseudoautosomal Regions (PAR): These are regions at the tips of the Y chromosome that can recombine with the X chromosome.         * PAR1: Located on the short arm (p-arm).         * PAR2: Located on the long arm (q-arm).     * Male-Specific Portion of the Y (MSY): This represents the bulk of the chromosome and does not recombine with the X.     * Chromatin Composition:         * Euchromatin: Gene-rich, loosely packed DNA.         * Heterochromatin: Densely packed, largely repetitive DNA.     * Sequence Classes within the MSY:         * X-degenerate: Relics of the ancient autosome from which X and Y evolved.         * X-transposed: Sequences moved from X to Y relatively recently in human evolution.         * Ampliconic (Segmentally Duplicated): Contains large, nearly identical repeats (palindromes).
• Palindromes and Gene Conversion:     * Palindrome Sequence Example: $\text{CTTGTACCATGTTC}$ followed by a space DNA and then the inverted sequence $\text{CTTGTACCATGTTC}$.     * Mechanism: The Y chromosome maintains its integrity through intra-chromatid crossing-over and inter-chromatid crossing-over during meiosis. This process, involving "hairpin" structures after palindrome binding, allows the Y to "repair" itself without a homologous partner.
• SRY Gene: The Sex-determining Region Y (Sry) protein binds to and bends DNA, triggering the developmental pathway for maleness.
• Structural Rearrangements and Deletions:     * AZF (Azoospermia Factor) regions: Crucial for sperm production. Deletions in these regions (AZFa, AZFb, AZFc, AZFd) lead to infertility.     * TSPY: A multi-copy gene (copy number variation recorded) involved in spermatogenesis.     * Inversions: Includes Yp paracentric inversions and pericentric inversions.

Y Chromosome Haplotypes, Surnames, and Ancestry

• Y Chromosome "Surnames": Because the Y chromosome is passed from father to son largely intact, it acts as a genetic surname or haplotype.     * Loci (DYS Markers): Minimal haplotype loci used in forensics and genealogy include $DYS393$, $DYS19$, $DYS391$, $DYS390$, $DYS389 I/II$, $DYS392$, and $DYS385a/b$.     * The Lemba and Cohanim Connection: Genetic studies found a shared Y-chromosome haplotype between the Lemba people of Zimbabwe and the Jewish Cohanim (priestly class). This supports the Lemba's oral tradition of Jewish ancestry.
• Surnames and Genetic Kinship:     * Men with rare surnames (e.g., Attenborough, with approximately $932$ bearers) are highly likely to share a specific Y chromosome haplogroup.     * Men with common surnames (e.g., Smith, with approximately $560,000$ bearers) show a diverse range of haplogroups ($E1b1b1$, $G$, $H$, $J2$, $IT$, $N1c$, $Q^<em>$, $R1^</em>$, $R1a$, $R1b1$), indicating they do not share a recent common male ancestor.
• Admixture Mapping: White genes in Black American populations show a disparity between maternal and paternal inheritance, with a significantly higher percentage of white paternal Y chromosomes compared to maternal white mitochondria:     * New York: Maternal White Mitochondria = $9.11\%$, Paternal White Y = $18.58\%$     * Philadelphia: Maternal White Mitochondria = $2.84\%$, Paternal White Y = $23.55\%$     * Pittsburgh: Maternal White Mitochondria = $9.90\%$, Paternal White Y = $23.87\%$     * New Orleans: Maternal White Mitochondria = $7.04\%$, Paternal White Y = $46.88\%$

Cytoplasmic Inheritance and Variegation

• Mirabilis jalapa (Four O'Clock Plant): Experiments by Carl Correns demonstrated non-Mendelian inheritance of leaf color (variegation).     * Phenotypes: All-white branches, all-green branches, and variegated branches.     * Inheritance Rule: The phenotype of the progeny is determined solely by the Egg Parent (Maternal Inheritance).         * White ($\text{Egg Parent}$) $\times$ white/green/variegated ($\text{Pollen Parent}$) $\rightarrow$ All White Progeny.         * Green ($\text{Egg Parent}$) $\times$ white/green/variegated ($\text{Pollen Parent}$) $\rightarrow$ All Green Progeny.         * Variegated ($\text{Egg Parent}$) $\times$ Green/White/Variegated ($\text{Pollen Parent}$) $\rightarrow$ A mixture of Green, White, and Variegated progeny.     * Mechanism: Progeny phenotype depends on which type of chloroplasts (white, green, or mixed) are present in the egg cell at the time of fertilization.
• Chlamydomonas Drug Resistance: Research by Ruth Sager on this single-celled alga.     * Finding: Resistance to certain drugs is inherited uniparentally from the "+" mating type parent ($mt^+$), not both parents.     * Cross: $\text{Resistant } (+ Parent) \times \text{ Sensitive } (- Parent) \rightarrow \text{ All Resistant Offspring}$.     * Cross: $\text{Sensitive } (+ Parent) \times \text{ Resistant } (- Parent) \rightarrow \text{ All Sensitive Offspring}$.

Organelle Genomes

• Chloroplast Genome (cpDNA):     * Structure: Circular DNA moleule.     * Key Genes: rps12, rps7, ndh2, rbcL (large subunit of RuBisCO), atpB, atpE, psbA, and ribosomal RNAs ($16S$, $23S$, $4.5S$, $5S$).     * Features: Includes Large Single Copy (LSC) and Small Single Copy (SSC) regions, along with Inverted Repeats (IRA and IRB).
• The Fungus Neurospora: Inherits mitochondrial traits via the maternal parent (protoperithecium).     * [poky] mutant: A mitochondrial mutation causing slow growth.     * Cross: $[poky] \text{ female} \times \text{Normal male} \rightarrow \text{All [poky] spores}$.     * Cross: $\text{Normal female} \times [poky] \text{ male} \rightarrow \text{All normal spores}$.
• Mitochondrial DNA (mtDNA):     * Human mtDNA: A circular genome of approximately $16,569\,\text{bp}$.     * Gene content: Includes $13$ proteins involved in oxidative phosphorylation (ND1-6, ND4L, COX1-3, ATP6, ATP8, Cytb), $22$ tRNAs (labeled with single letters like TRNF, TRNV, etc.), and $2$ rRNAs (RRNL, RRNS).     * Control Region (CR): Contains hypervariable regions (HV-I, II, III) used in forensic identification.
• Endosymbiotic Theory: Proposed by Lynn Margulis.     * Summary: Eukaryotic organelles (mitochondria and chloroplasts) originated as free-living aerobic or photosynthetic bacteria that were engulfed by a host cell and became symbionts.

Mitochondrial Disease

• Pedigree Patterns: Mitochondrial diseases are passed through mothers only, to both sons and daughters. Affected fathers do not pass the trait to their offspring.
• The Bottleneck Effect: During oogenesis, a small, random sample of the mother's mitochondria is selected to populate the egg cell. This can lead to a drastic shift in the proportion of mutant versus healthy mitochondria in the offspring compared to the mother.
• Key Pathological Feature: Ragged Red Fibres are often seen in muscle biopsies of patients with mitochondrial disease, representing an accumulation of abnormal mitochondria.
• Organ Vulnerability: Tissues with high energy demands are most affected:     * Nervous System: Seizures, tremors, developmental delays, stroke before age $40$, dementia, and poor balance.     * Eyes: Ptosis (drooping eyelids), external ophthalmoplegia (inability to move eyes), and blindness (retinitis pigmentosa).     * Heart: Cardiomyopathy (heart failure, conduction block).     * Skeletal Muscle: Weakness, exercise intolerance, and cramps.     * Other: Pancreas (diabetes), Kidneys (Fanconi syndrome), and Digestive tract (acid reflux, vomiting).
• Specific Disorders:     * LHON (Leber Hereditary Optic Neuropathy): Characterized by sudden loss of central vision; optic discs appear small with no central cup.     * MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes.     * MERRF: Myoclonic Epilepsy and Ragged Red Fiber disease.     * NARP: Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosum.     * KSS (Kearns-Sayre Syndrome): Associated with large mtDNA deletions.     * MILS: Maternally Inherited Leigh Syndrome.     * ADPD: Alzheimer's Disease and Parkinson's Disease (some associations).

Mitochondrial Replacement Therapy (MRT)

• Procedure: Often referred to as "three-person babies."
• Method (Egg Repair):     1. The nucleus is removed from the mother’s egg (which contains unhealthy mitochondria).     2. The nucleus is removed and destroyed from a healthy donor egg.     3. The mother’s nucleus is inserted into the enucleated donor egg, which contains healthy mitochondria.     4. The resulting egg is fertilized and implanted.
• Status: In February $2015$, UK MPs voted in favor of the procedure. The first baby born from this technology in the UK was reported in May $2023$.