Sex-Linked Heredity and Sex Determination BMS 532 PDF

Sex-Linked Heredity and Sex Determination BMS 532 BLOCK 2 LECTURE 6  Objectives 1. Define the following terms: homogametic, heterogametic, hemizygous, haploinsufficiency, nondisjunction, genic, environmental, and sexual determination. 2. Compare and contrast sex chromo...

Sex-Linked Heredity and Sex Determination BMS 532 BLOCK 2 LECTURE 6  Objectives 1. Define the following terms: homogametic, heterogametic, hemizygous, haploinsufficiency, nondisjunction, genic, environmental, and sexual determination. 2. Compare and contrast sex chromosomes and sex determination across species 3. Explain the distinction between a homogametic and heterogametic individual in XX/XY and ZZ/ZW sex determination 4. Assess the outcomes for a given mating under XX/XY and ZZ/ZW organisms in terms of biological sex expectations and features associated with or influenced by sex chromosomes 5. Evaluate the consequences of changes in genes, environment, and sex chromosome content for sex determination and development of secondary sexual characteristics ◦ Outline how climate change is proposed to be altering male:female ratios in turtles, alligators and crocodiles 6. Compare and contrast the X and Y chromosomes 7. Explain why it is necessary to have regions of similarity between the human X and Y chromosomes 8. Using the Morgan Fruit Fly experiments as a foundation, assess outcomes for a given mating and explain the role of reciprocal crosses in defining sex-linked inheritance ◦ Summarize Morgan’s and Bridge’s fruit fly experiments and their outcomes 9. Explain X-linked inheritance in terms of human health and disease and Explain the consequences for nondisjunction in terms of genotype and phenotype 10. **Determine probabilities for offspring inheriting a particular trait (autosomal vs. sex-linked) LO1 Terminology Sex Chromosomes = chromosomes that contain the genetic information necessary to confer biological sex and influence development of secondary sexual characteristics Homogametic = has gametes with the same sex chromosomes Heterogametic = has gametes with different sex chromosomes Hemizygous = containing only 1 copy of a chromosome that can be or is typically observed in a pair Haploinsufficiency = loss of 1 copy results in a situation where the remaining copy cannot compensate and make sufficient product; reduced function is expected due to the insufficient levels of product ◦ NOTE: genes exclusive to the Y or X in humans are NOT haploinsufficient as proper gene dosage is 1 ◦ This is why some genes on the X MUST be inactivated (see epigenetics lecture) LO2 Sex Chromosomes and Sex Determination In sexual reproduction, differences between the 2 sexes are established by key genes often located on specific sex chromosomes Sex chromosomes can vary across different organisms Sex chromosomes do NOT have to involve 2 distinct chromosome types in the pair ◦ Humans: XX females vs XY males ◦ Grasshoppers: XX females vs XO males (males have fewer chromosomes than females) When the chromosome pairing involves one biological sex having fewer chromosomes, meiosis will result in gametes that have unequal chromosome numbers LO1, LO2, LO3, LO4 More on Sex Chromosomes and Sex Determination Heterogametic Sex = sex with 2 different chromosomes ZZ vs ZW ◦In many species, the heterogametic sex is the female ◦This system is found in birds, snakes, butterflies, some amphibians and some fish LO1, LO3, LO4 XY Heredity (Humans) In humans, males are heterogametic X and Y can pair during Meiosis because of structural similarity in the chromosomes (regions of homology) ◦ Pseudoautosomal regions Crossing-over occurs in these regions Because these are regions of similarity that do contain genes, these regions escape X- inactivation ensuring proper gene dosage for those genes LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) While biological sex is frequently determined by genes, the location of those genes can very especially if there are no sex chromosomes ◦No visible difference in the chromosomes of males and females and no sex chromosomes Genic Determination ◦Genes at one or more loci determine sex without specific sex chromosomes LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) Environmental Sex Determination ◦Environment is either partially or completely responsible for sex determination ◦Organism has equal chance to be either sex but cannot be both at the same time ◦Ex: slipper limpet (Crepidula fornicata) ◦Sequential hermaphroditism LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) Environmental Sex Determination ◦Reptiles including turtles, crocodiles, alligators and some birds ◦ Temperature-based sex determination https://www.sciencedirect.com/science/article/abs/pii/S0006320717308534 LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) Environmental Sex Determination ◦ For turtles, warmer temperatures result in more females, colder temperatures yield more males ◦ For alligators, colder temperatures result in more females, warmer temperatures yield more males ◦ For bearded dragon lizards, environment influences the phenotype rather than the genotype. ◦ ZZ is male except when the embryo is incubated at high temperatures, then ZZ is phenotypically female even though genotypical male. https://www.sciencedirect.com/science/article/pii/B9780123749307100019 LO1, LO2, LO5 Sex Determination without Sex Chromosomes (Genic or Environmental) Environmental Sex Determination ◦Crocodiles ◦Sex determination is more complex ◦32-33°C nest temperature = male crocs ◦Any other temperature = females https://www.sciencedirect.com/science/article/pii/B9780123749307100019 LO1, LO2, LO5 Global Warming and Sex Determination Increasing global temperatures for sex determination based on temperature is altering the ratio of males to females and disrupting reproductive potential All Mal e All Femal e https://onlinelibrary.wiley.com/doi/full/10.1111/eva.13226 LO1, LO2 Mammalian Biological Sex Determination Genes typically located on the Y chromosome confer key proteins for defining the production of testes Loss of genes in an XY individual will result in phenotypical development as female Phenotypic development as female with functional ovaries in the absence of genes is not guaranteed thus there is no actual biological default sex as previously thought Presence of small portions of the Y chromosome in XX individuals has been shown to be sufficient to cause phenotypical male development implying only a small portion of the chromosome is actually needed for sex determination LO1, LO2, LO6 Human Biological Sex Determination SRY gene on Y chromosome confers testes development ◦ Transcription factor ◦ Activation of the gene occurs at roughly 6 weeks development ◦ Prior to the activation of key genes gonads are undifferentiated ◦ SRY is located in close proximity to the pseudoautosomal region Once triggered, testes begin to form and secrete ◦ Testosterone to promote development of male characteristics and ◦ Mullerian inhibitory substance (MIS) to suppress/degenerate female reproductive ducts In the absence of SRY, ovaries can develop (estrogen and no MIS) Absence of proper gene activity can hinder development and result in sterility LO6, LO7 More about the X and Y Chromosomes Although the main components of sex determination are located on these chromosomes, autosomal genes are also important ◦ There are actually more genes associated with sexual development on the autosomes but they require activation typically triggered by the genes on the sex chromosomes The X and Y chromosomes also contain genes NOT associated with sexual development ◦ The inheritance of those genes do not follow Mendel’s laws Males in XY inheritance are hemizygous (only one copy of some genes) LO6, LO7 More on Pseudoautosomal Regions Distal region of short arms of X and Y = highly similar DNA sequences (PAR1) ◦ Areas for crossing over in male meiosis that resembles autosomal crossing-over Region of homology at distal end of long arms that also experience alignment and crossing-over (PAR2) All genes within PAR1 are NOT inactivated in women ◦ Need 2 copies (dosage compensation) There is a high recombination frequency in PAR1 LO1, LO2, LO3, LO4 Summary LO1, LO2, LO8 Sex-Linked Inheritance Inheritance patterns for genes on the sex chromosomes differs from that for autosomes Since the X chromosome has more genes located on it, most sex-linked inheritance is condensed to X-linked inheritance Sex-linked inheritance results in differential expression of traits between males and females Thomas Hunt Morgan and his fruit fly experiments were a major series of experiments demonstrating X-linked inheritance with differential expression of traits between males and females LO8, LO9 Morgan’s Crosses Parental Generations 2 crosses that are reciprocal parents are needed to define X-linked inheritance ◦ 1) Red-eyed female x White-eyed male ◦ Offspring = All Red Eyes (no difference between males and females) ◦ Morgan then took these offspring (F1) and crossed them (generated F2) ◦ 2) White-eyed female x Red-eyed male ◦ Offspring = All Red-eyed Females and All White-eyed males ◦ Morgan then took these offspring (F1) and crossed them (generated F2) 19  Morgan’s Crosses F1 crosses ◦ 1) Heterozygous Female x Red-eyed Male ◦ All females red-eyed ◦ Half the males white-eyed ◦ 2) Heterozygous Female x White-eyed Male ◦ 50% red-eyed males and females ◦ 50% white-eyed males and females The discrepancy between males and females in presentation of the phenotype is a hallmark of X- linked or sex-linked inheritance 20 LO8, LO9 LO8, LO9 Morgan’s Fruit Fly Experiments Summary Morgan’ s genetic principles: Sex-linked inheritance based on mutations observed in males only Gene linkage based on the inheritance of genes as a single unit Chromosome mapping based on recombination frequencies between linked genes  Deviations from Expectations Morgan’s cross shown here should produce 100% red eyed F1 flies. Out of 1237 F1 flies screened, 1234 had red eyes ◦ Three white-eyed male flies were observed Further similar crosses continued to produce a low frequency of white-eyed males that was too high to be explained by random mutation. Calvin Bridges was assigned by Morgan to work on the problem LO8, LO9 22  Bridge’s Experiments in Fruit LO8, LO9 Flies: Nondisjunction After repeating several crosses similar to Morgan’s, Bridge discovered that only certain matings produced the unexpected results Bridges hypothesized that the exceptional white-eyed female strain possessed two X chromosomes and a Y chromosome. ◦ XXY flies develop as females and can exhibit recessive traits Bridges proposed that about 10% of the time during meiosis, the two X chromosomes fail to separate from each other ◦ Failure to properly separate chromosomes = Nondisjunction LO8, LO9 Nondisjunction More evidence for the chromosome theory of inheritance Failure to properly separate chromosomes leads to inappropriate gene content in the offspring Many of the genetic options produce nonviable offspring (embryonic lethal) ◦ YY (always) and XXX (usually) LO10 Example Time!! Autosomal vs Sex-Linked You are curious about a given trait and its inheritance. There are 2 variants of the trait with clear dominance. How could you determine whether the trait is autosomal or sex-linked? ◦What is your hypothesis? ◦What crosses would you perform? Autosomal vs Sex-Linked Human Color-Blindness Human color blindness is an X-linked trait. Define the expected outcomes for offspring if two individuals reproduce who are in pairings as follows: Homozygous NOT Color-Blind Female x Color-Blind Male Heterozygous Female x Not Color-Blind Male Heterozygous Female x Color-Blind Male