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SEX CHROMOSOMES

Most species have a defined number of HOMOMORPHIC (same shape) autosomes. In some species, these may influence gender morphology & development.

Usually, however, sex is determined by one (or more) pair(s) of HETEROMORPHIC sex chromosomes. In humans and other mammals, these are the sex chromosomes, X and Y (which some people have mapped a little bit differently).


The human Y chromosome has relatively few gene loci compared to the X chromosome.

The X and Y have homologous regions (i.e., with matching gene loci) which pair up during meiosis (synapsis) and undergo limited crossing over. These regions of homology are called PSEUDOAUTOSOMAL regions.

Most of the X and Y are not homologous, however, and undergo NO CROSSING OVER. Traits coded on this DIFFERENTIAL regions of the X and Y exhibit inheritance patterns that are quite different from those shown by autosomal genes, and may be

  • X-linked (located on the differential region of the X c'some)
  • Y-linked (located on the differential region of the Y c'some).

  • Y-linked traits, which exist only in males, are known as HOLANDRIC traits. Under normal circumstances, females never express them.

  • Recall that when an individual has the normal number of chromosomes (two per homologous pair), then each trait on a given chromosome is either
  • Because males have only one allele for (almost all) genes located on the X chromosome, they are said to be HEMIZYGOUS for those X-linked traits. They have only ONE copy instead of two. This can spell trouble!

    The X chromosome has a large number of functional genes, whereas the Y is believed to have relatively few. A human can survive with a sex chromosome genotype of Xo, but not with Yo, since many vital genes are located on the X.


    Sex Chromosomes and their Special Inheritance

    Consider an important implication of the XX and XY genotypes. Does this mean that females get twice the "dose" of the products on the X that males get?

    NO.

    This is prevented by the Amazing Phenomenon of DOSAGE COMPENSATION.

    Evidence supporting the Lyon Hypothesis: Humans with abnormal numbers of X chromosomes have one fewer Barr body than # of X chromosomes:


    Cytological analysis has revealed that the Barr Body is, indeed a little ring of supercoiled heterochromatin, mostly non-transcribable. The process of Barr Body formation is now called LYONIZATION.

  • In effect, each individual cell in a female's body is HEMIZYGOUS for traits on the X chromosome, as are males. However, because the random inactivation means that at least SOME of each of the two alleles are active, she won't express harmful X-linked conditions such as

  • There are exceptions, however: the 18 genes on the PSEUDOAUTOSOMAL REGION of the X chromosomes are not inactivated. As in males, both copies (on both X chromosomes) are actively transcribed and translated.

  • How do these 18 genes avoid being inactivated? We don't yet know!

  • However, the RANDOM inactivation still prevents full expression of deleterious recessives on the differential region, since normal X product will always be produced by at least some active X chromosomes.

  • A classic example: calico & tortoiseshell cats: One gene coding for fur color in cats is located on the X chromosome.

    Let's do a Punnett Square.

    The expression of genes on either one or the other X chromosomes throughout the body of a female mammal is known as MOSAIC EXPRESSION.
    (You all know what a mosaic is, right?)

    Mosaic expression is not always as visible as the color of cat fur.
    Most X-linked products are not obvious to the naked eye, and may be as subtle as two forms of an enzyme produced by in certain tissues of the body.



    Remember that X-LINKED traits should not be confused with SEX INFLUENCED TRAITS, which are autosomal, but expressed differently depending on the sex of the individual. Examples:

    More about SEX

    The ratio of males to females in a population is known as the SEX RATIO.

    The PRIMARY SEX RATIO is the ratio of males : females CONCEIVED.
    The SECONDARY SEX RATIO is the ratio of males : females BORN

  • All things being equal, what would you predict the ratio of males to females conceived would be?

  • All things being equal, what would you predict the ratio of males to females born would be? In reality, more males are conceived than females.

    Examples of PRIMARY SEX RATIOS (derived from huge numbers of abortions and miscarriages analyzed):

    Why do you suppose this might be?

    But wait! There's more! The SECONDARY SEX RATIOS of the above are:

    There is a decrease between PRIMARY and SECONDARY sex ratios! More males are conceived than females, but this number is higher than the number of males born compared to females.

    WHY?



    Some interesting X-linked traits:

  • hemophilia ("Bleeding disease") - traced back to Queen Victoria (recessive)
  • Androgen Insensitivity Syndrome (once called Testicular Feminization Syndrome) (recessive) - let's take a closer look.

    Before we can fully understand this, we must take a short foray into the Wonderful World of How Babies Become Boys or Girls.


    A model for sex initiation was first proposed by Eva Eicher and Linda Washburn (Jackson Lab) in 1986. Simplified, it goes like this...

    Here's a very simple diagram of the pelvic region of a very early (i.e., prior to 8 weeks) human embryo.

    "Androgen Insensitivity Syndrome" (rare; X-linked) is a mutation which inactivates one such protein portal which serves as an androgen receptor in the plasma membrane found in normal males.

    A person with AIS has:

    WHY?

  • When sry turns on at 8 weeks, the generalized gonads are changed into testes. These are present in the AIS adult, either up in the groin or descended into the labia, and secrete normal amounts of testosterone.

  • Because the testosterone cannot enter the cells to turn the "male determining" genes on/off, the cells follow the "default" pathway, which is female.

  • The resulting phenotype is that of a female, though genotype is XY.
  • The individual is sterile: there are no internal Mullerian structures (no uterus, fallopian tubes or ovaries), and only a blind-end vagina.

    Certain structural genes on the Y c'some are still operational, and are expressed normally. For example, persons with this syndrome often have...


    Another form of human pseudohermaphroditism is 5-AR Deficiency

    Treatments once included surgical "repair" of external genitalia. Before this condition was fully understood, parents of 5-AR deficient individuals were often given the option of choosing a gender for the child. Unfortunately, because testosterone-driven development is that of a normal male, this adversely affected the psyche of many individuals who were "forced" to become female without their consent.

    Well-informed practitioners generally do NOT recommend feminization of these male individuals as a treatment option.