Sex Linkage and Determination 1 In humans fruit

Sex Linkage and Determination 1 • In humans, fruit flies, XX = female; XY = male. • Because there are genes on sex chromosomes, inheritance of certain traits can be sex-linked. • Early 1900 s, Thomas Hunt Morgan was doing classical genetics on fruit flies, looking for mutants and checking out the patterns of inheritance. • He studied the white eye phenotype and discovered something odd…

What Morgan saw Reciprocal cross produced a different result: Inheritance of eye color depended on sex of the fly. 2

Morgan and the F 2 generation When the all red eyed F 1 heterozygotes were crossed, a 3: 1 ratio was observed, but not evenly divided between the sexes. 3

significance • With regard to X linked traits, males have only one allele, not two. They are said to be hemizygous. • Morgan’s work led to the understanding that genes are located on chromosome’s because inheritance of certain traits corresponded to inheritance of a visibly different chromosome. • Inheritance of X-linked traits results in typical crisscross inheritance: mother to son. 4

Crisscross inheritance 5 Carrier mother passes allele to son who expresses it, passes allele to daughter who carries it, etc. Hemophilia & color blindness: examples in humans. http: //www. udl. es/usuaris/e 4650869/docencia/segoncicle/genclin 98/temes_teoria/imatge s_temes_teoria/image 3. gif

Sex determination 6 • Different organisms have different chromosomal mechanisms for determining sex. – XX/XO: typically, the male has one copy. • Nematodes, e. g. C. elegans – XX/XY: as in humans, fruit flies, XX = female; XY = male. • Heterogametic sex is the one that produces a mixture of gametes. Usually the male but: – Female can be heterogametic in some species – Designation is ZZ/ZW where female is ZW

More on sex determination 7 • Temperature affects sex determination in many reptile species – Females result from low, high, or extremes of temperature. – Hypothesis:

History 8 • Sex determination studies began in late 1800’s • Work in humans started around 1912, but didn’t get it right until 1956. • Keys to understanding sex determination in humans: – Improved karyotype methods – Study of aneuploidy of sex chromosomes – Aneuploidy is the wrong number of a particular chromosome. – Aneuploidy results from non-disjunction

Abnormalities in chromosome number result from non-disjunction Homologues fail to separate during Meiosis I. 9

Abnormalities in chromosome number result from non-disjunction-2 Sister chromatids fail to separate during Meiosis II. 10

Evidence for XX/XY 11 • 47, XXY Klinefelter syndrome – male in appearance, but some feminization; sterile. – slow to learn, but not retarded. – XXXY etc. similar, but more severe symptoms • 45, XO Turner syndrome – Monosomy, the only one occurring in humans – female, sterile, short webbed neck, broad chest, short. – majority aren’t born • If XXY is still male and XO is female – Y must be determinant of maleness

Other sex chromosome aneuploidies 12 • 47, XXX – Some phenotypically normal – Others, sterility, mental retardation • 47, XYY – 1965 study: higher number of inmates with XYY – revisited: no real correlation with criminal behavior • Controversial research, no clear answer. – taller than average, slightly lower IQ on average.

About the Y 13 • Y chromosome has been shrinking. – Now missing many of genes that X has. • Two regions: PAR and MSY • PAR= pseudoautosomal region – Regions near p telomere and q telomere are homologous to X chromosome. Crossing over can occur there during meiosis. Because of this, genes in this location do not behave as sex-linked traits, thus said to be pseudoautosomal because they behave like genes on autosomes rather than sex chromosomes.

Male specific region Y 14 • X-transposed region – 99% identical to X chromosome region, but only 2 genes; the rest are not expressed. • X-degenerative region – Contains DNA related to X chromosome regions – Several functional genes – Contains SRY that codes for testis-determining factor, necessary for maleness during development. • Ampliconic region – Highly similar genes related to male development and fertility.

Evidence for SRY 15 • SRY contains gene for testis determining factor • Crossing over in meiosis – Males with two X chromosomes; SRY found on one – Females with X and Y; SRY is missing from Y • Transgenic mice – Remove SRY from Y chromosome – Mice are XY but are female – Reciprocal experiment also done

Gene dosage 16 • It matters how many copies of genes there are. – Snapdragons: heterozygous flowers are pink. – Multiple histone genes. – Too many of some genes is deleterious. • 3 copies of chromosome 21 = Down Syndrome • What about sex chromosomes? XX vs. XY – Y chromosomes are missing most of genes X has. – So, if 1 set of genes on the X is good for males, is two sets (2 X chromosomes) bad for females?

Dosage compensation: Barr, Ohno, and Lyon 17 • Barr noticed that in the nucleus of females, but not males, a darkly staining body is visible. • Ohno hypothesized that this was an inactivated X chromosome in females so that there would only be 1 functional copy of genes, as in males. • Inactivated X is called a Barr body. • Individuals with incorrect numbers of sex chromosomes have appropriate number of Barr bodies. – E. g. XXX females have 2 Barr bodies

Lyon Hypothesis 18 • X chromosome inactivation takes place early in development. • In placental mammals, it can be either X chromosome. – All the descendents of that cell have the same X chromosome inactivated. – Results in a mosaic, patches of tissue with different lineages. • Human females: anhidrotic epidermal dysplasia, no sweat glands; X linked gene, female has patches of skin w/o sweat glands, cells descended from a cell in which the X chromosome with the normal gene was inactivated. • G 6 PD alleles; Patches of color blindness

19 Descent of cells: How mosaics are made. Two homologous chromosomes, blue & red. Black indicates inactivation = Barr body

Formation of Barr bodies-2 Classic example: the calico cat. One X chromosome codes for orange fur, the other for black. Cat shows characteristic mosaic patterns caused by one or the other X chromosome being inactivated. White fur results from the effect of another gene. http: //www. petstreetmall. com/merchant/Embroidery/Cat/Calico. Cat. Body. gif. jpe 20

Molecular basis of Barr body formation 21 • Xic is a region on the X near the centromere. • Xic region includes a region called Xist (X inactivation specific transcript) – This area is transcribed, but RNA isn’t used to make a protein; it binds to the DNA of the rest of the X chromosome. – This promotes molecular changes that inactivate the chromosome including extensive methylation (except for XIC) and condensation of DNA (into smaller space). • In the OTHER X chromosome, Xic region is methylated so it will NOT be active.

Active and inactive regions Red: active genes. Black: inactive 22

Human sexuality • http: //info. med. yale. edu/therarad/summers/wgss 255 a%20 lecture%2013. ppt#1 • Interesting powerpoints with more questions than answers – Caution: graphic images 23