The genetics of sex

Mitosis Meiosis I Meiosis II Ploidy at start Preceded immediately by DNA synthesis Chromosomes condense Homologous chromosomes synapsis Genetic material is exchanged Homologous chromosomes separate Sister chromatids separate Daughters have novel genetic composition Ploidy at end

When does meiosis occur in humans? What happens when there are errors in meiosis? What determines sex in humans? How do males and females balance their gene products?

Meiosis in mammalian males doesn’t begin until puberty Germ cells Male germ cells continue to proliferate throughout adult life Four similar spermatozoa are produced from each germ cell

Meiosis in mammalian males begins after puberty Germ cells line the perimeter of the tubule Somatic (non-germ) cells nurture the developing sperm As sperm mature, they move toward the central lumen Process takes ~3 weeks to a month

Females are born with ~1 million oocytes More than half die before puberty A cohort of follicles begins to grow in response to hormones each month (takes ~1 year) – most will die Dominant oocytes resume meiosis and arrest in metaphase II when they are ovulated Prophase I arrest Meiotic divisions are asymmetric, producing a single large gamete, the oocyte

Oocytes are surrounded by many supporting cells within a follicle Ovarian follicles at various stages of differentiation can be seen in a cross-section of an ovary. Period of growth from a primary follicle (2) to ovlulation (4) takes about a year

In mammals, there are important distinction between meioses in males and females. Which of the following is NOT true? In females, oocytes are arrested in meiosis for most of the lifespan. Meiosis occurs throughout the lifespan of human males. Male meiosis produces four spermatozoa, each with a unique genetic composition Female meiosis produces one functional oocyte and three small, haploid polar bodies Meiosis begins earlier in females than in males

When does meiosis occur in humans? What happens when there are errors in meiosis? What determines sex in humans? How do males and females balance their gene products?

Aneuploidies arise from errors in either meiosis I or meiosis II Segregation errors cause cells to have too many or two few chromosomes

Error in meiosis I Homologs don’t separate or don’t attach to spindle Trisomies (too many chromosomes) Monosomies (too few chromosomes) Error in meiosis II Centromeres don’t separate or don’t attach to the spindle

Human genome encodes ~21,000 proteins Chromosome Protein coding genes Few human trisomies are tolerated – may relate to the number of genes that encode proteins Human genome encodes ~21,000 proteins Chromosome Protein coding genes Incidence at birth % survival after 1 year 1 2102 13 (Pateau) 318 ~1/15,000 <5% 18 (Edward) 268 ~1/8000 21 (Down) 225 ~1/800 85% 22 431 very rare X 815 1/1000 females very good Y (XYY – Jacob’s) 45 1/1000 males Sex chromosomes aneuploidies are tolerated

Individuals with Klinefelter Syndrome (47, XXY) are males, but sexual development is impaired Some male and female development, but no sperm 2 in 1000 male births

Individuals with Turner Syndrome (45, X) are females only viable human monosomy Female development, but no eggs. 1 in 3000 female births Symptoms may relate to haploinsufficiency for multiple gene products

When does meiosis occur in humans? What happens when there are errors in meiosis? What determines sex in humans? How do males and females balance their gene products?

Y chromosome genes determine male-specific traits The presence of the Y chromosome normally determines whether a human is male or female Y chromosome genes determine male-specific traits Analysis of chromosomes in intersex individuals was critical to understanding sex determinants

The X and Y chromosomes pair up during male meiosis Tips of the Y chromosome (pseudoautosomal region) exchange with the X chromosome during meiosis Much of the Y does not recombine with the X – this region hosts genes important for male fertility Autosome: non-sex chromosome Humans have 22 pairs of autosomes

Y chromosome is gene-poor, but retains important genes Other genes remain similar to those on the X - mostly housekeeping genes Y chromosome is a degenerate X chromosome - many inversions and deletions have occurred over evolutionary time Y chromosome has key genes important for male development and fertility

Functions and evolution of the Y chromosome HHMI Holiday lecture on sex determination (17 min.) Lecture 4, Parts 7-15

When does meiosis occur in humans? What happens when there are errors in meiosis? What determines sex in humans? How do males and females balance their gene products?

Mammals use X-inactivation to ensure male and females have similar amounts of proteins produced from X chromosome genes The Barr body: the inactive X is highly condensed and can be visualized with the light microscope Female Male Canadian scientists Murray Barr and Ewart Bertram noted that male and female neurons could be distinguished by the absence (male) or presence (female) of a heterochromatic structure Barr and Bertram (1949) Nature :676-677

How many Barr bodies would you expect in an XXY male with Kleinfelter’s syndrome? None One Two Three

How many Barr bodies would you expect in an individual with Trisomy X? None One Two Three

X-inactivation is an example of epigenetics Calico cats provide a familiar example of X inactivation Calico cats are always females Alleles for orange and black coat color are on the X Cats are mosaics - one X chromosome is inactivated in each cell in a random pattern established in early development (White spotting pattern determined by another gene) X-inactivation is an example of epigenetics

X-inactivation and calico cats

A female calico cats mates with a black male cat and has a litter of 10 kittens. The female kittens are: All black All calico Half black and half orange Half black and half calico Half orange and half calico

A female calico cats mates with a black male cat and has a litter of 10 kittens. The male kittens are: All black All calico Half black and half orange Half black and half calico Half orange and half calico

Discuss: Why do individuals with Turner’s syndrome have reduced fertility and other symptoms?