Sex Determination and Sex Chromosomes

Vocabulary:

• Sex: Refers to sexual phenotype, male or female or intersex, mostly differ in gamete size with females having larger gametes

• Meiosis: The process of cell division that generates haploid gametes from diploid cells

• Sexual reproduction: Allows for far more variation among a species, consists of cycles of meiosis and fertilization, switches from haploid to diploid

• Sex determination: The mechanisms by which biological sex are established

• Gender: Different than sex, more of a social construct, assigned by the individual of others based on behavior and cultural practices, doesn’t necessarily coincide with biological sex

• Hermaphroditism: A condition where both sexes exist in the same organism

• Monoecious: An organism that contains both male and female reproductive structures in the same organism

• Dioecious: Organisms that contain either male or female reproductive structures in one organism, requiring another organism of the opposite sex to reproduce, like humans. Sex is determined either chromosomally, genetically, or environmentally

• Phenotypic dimorphism: Differentiation of sexes that is evident

• Heteromorphic chromosomes: Chromosomes that are visibly dissimilar in size and structure, unlike autosomes

• Sex chromosomes: Characterize one sex or the other in a wide range of species

• Protenor: A mode of sex determination, depends on the random distribution of the X chromosome into half of the male gametes, XX results in female while XO results in male

• Lygaeus: A mode of sex determination, female gametes all have an X chromosome and male gametes have either an X or a Y

• Homogametous: When a zygote contains two of the same sex chromosome. An organism like this will produce like chromosomes, and result in female offspring

• Heterogametous: When a zygote contains 2 different sex chromosomes. An organism like this will produce unlike chromosomes, will result in male offspring

• ZZ/ZW: A mode of sex determination where females are heterogametic and makes are homogametic. Common in birds, butterflies, and moths

• Genic: A mode of sex determination where there are no heteromorphic sex chromosomes, and no obvious difference between males and females. Sex is typically determined by multiple genes, with some environmental influence. Found in some plants, fungi, protozoa, and fish

• Environmental Sex Determination: A mode of sex determination that varies based on environmental surroundings, for thinks like position or temperature

• Turner Syndrome: Has the sex chromosome XO, results from nondisjunction, present female but have underdeveloped breasts and stalling of sexual development during teenage years. Tend to be short, have cognitive impairment, and be sterile

• Klinefelter Syndrome: Has the sex chromosomes XXY or rarely XXXY, XXXXY, or XXYY. Results from nondisjunction. Present male, tend to have long arms/legs, be taller, have large hands/feet, and fail to produce sperm. Also have enlarged breasts and rounded hips as female development isn’t suppressed

• Poly-X: Has many different X sex chromosomes

• Triplo-X / XXX Syndrome: The presence of 3 X chromosomes along with a normal set of autosomes, present female and tend to be perfectly normal. Sometimes taller than average with widely spaced eyes and weak muscle tone. Can also have underdeveloped secondary sex characteristics, be sterile, and have cognitive impairment. The more X chromosomes there are, the more cognitive impairment there tends to be

• Jacob’s Syndrome: Has the sex chromosomes XYY, males tend to be over 6 feet tall and have an increased risk for asthma, seizure, autism, and learning disabilities. Can have personalities, and live normal lives

• Y-Chromosome: A sex chromosome that contains fewer genes than the X counterpart, has pseudoautosomal regions (PARs), MSY

• Pseudoautosomal Regions (PARs): Parts of the Y chromosome that share homology with regions on the X chromosome, and synapse and recombine with it during meiosis, critical to the segregation of the X and Y chromosomes during male gametogenesis

• Male specific region Y (MSY): A male specific region on the Y-chromosome, largely non-recombining with the X-chromosome. Contains some genes that were originally derived from the X-chromosome, contains the SRY subregion

• SRY: A subregion of the Y-chromosome’s MSY region, this part is the sex determining region containing the genes required to develop as a male, located adjacent to the PAR of the short arm, encodes TDF

• Gonadal primordia: Tissues that will form gonads, formed by the fifth week of gestation, arise as a pair of gonadal ridges associated with each embryonic kidney

• Bipotential gonads: Gonadal ridges that can form either ovaries or testes

• Male development: Results from a ridge cell having XY, medulla develops into testes. Embryonic testicular tissue will secrete hormones for male sex development, activation of some hormones causes regression and degradation of Mullerian ducts, primary spermatocytes are produced at puberty

• Female Development: Develops without Y and no male development, cortex of the ridge subsequently forms female reproductive structures and Mullerian ducts persist. Absence of testosterone causes the wolffian duct to degenerate, and by the 12th week oogonia within ovaries undergo meiosis and form primary oocytes. By week 25, all oocytes are arrested in meiosis and are dormant until 10-15 years

• Sexual dimorphism: Distinct difference in size of appearance between the sexes of an animal in addition to the difference between the sexual organs themselves

• Primary sexual differentiation: Sexual difference between gonads, where gametes are produced

• Secondary sexual differentiation: Overall phenotypic distinguishments for the sex of an organism, not including gonadal differences, includes things like mammary glands, genitalia, and other traits

• Testis-Determining Factor (TDF): A protein that activates in XY embryos around 6-8 weeks, triggers testes formation which then go one to release testosterone and anti-Mullerian hormone

• X-Transposed Region: Part of MSY, 15%, derived from the X chromosome and contains 2 genes homologous to genes on X

• X-Degenerative Region: Part of the MSY, 20%, has 27 single copy genes and many pseudogenes, shares some homology with X, contains the SRY which is only expressed in testes

• Ampliconic region: Part of MSY, 30%, crucial for fertility as it encodes proteins specific to testis development and function, lack X homology

• Androgen receptor (AR): Mediates the actions of androgens like testosterone, its a ligand-dependent nuclear transcription factor and steroid hormone nuclear receptor, gene for this is X-linked

• Androgen-insensitivity syndrome: Caused by a defective AR, someone may be XY but resistant to male hormones, resulting in a female phenotype. Menstruation doesn’t occur and vagina ends blindly with no uterus, oviducts, or ovaries. Testes in the abdominal cavity produce levels of testosterone regular in males

• Paternal Age Effects (PAE): Advances paternal age is associated with an increased risk in offspring of congenital disorders, cancers, schizophrenia. These come from mutations being positively selected for in the Y-chromosome of sperm

• Primary sex ratio: Reflects the proportion of males to females conceived in a population, 1:1 in humans as discovered by Orzack et al. in 2015

• Secondary sex ratio: Reflects the proportion of each sex that is born, for humans tends to be more female:male as male fetal mortality is higher

• Dosage compensation: Balances the dose of X chromosome gene expression in females and males, as females can produce excessive expression of X-linked genes. The additional X in females is inactivated and becomes highly condensed

• Barr Bodies: The condensed chromosome structure, a sex chromatin body, observed in stained interphase cells, inactive X chromosome in female somatic cells

• Lyonization: The process that renders the extra X chromosome inactive and creates the Barr body, part of dosage compensation

• Lyons Hypothesis: Proposed in 1961, the Barr body is an inactive X-chromosome, chosen randomly in embryonic development. All cells descended from each original cell that randomly deactivates will maintain the same pattern of parental inactive X

• X-inactivation: Explains dosage compensation, follows N-1 rule where N is the number of X chromosomes, indirect evidence includes sex-chromosome syndromes, doesn’t impact Turner of Klinefelter syndromes

• G6PD: Synthesis of this enzyme is controlled by a X-linked gene, proved random permanent inactivation of the X chromosome

• X-inactivation center (Xic): A region of the mammalian X chromosome that is the major control unit for X-inactivation, located near the centromere, has several putative regulatory units and 4 genes, contains XIST, Tsix, and Xite

• X-inactive specific transcript (XIST): Encodes for structural RNA that is a long noncoding RNA (lncRNA) critical for X inactivation, functions by coating the inactivated X

• Mosaicism: Can result from dosage compensation, a trait is expressed in parts/patches