Gene dosage 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 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 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. Seen with X-linked traits. Human females: anhidrotic epidermal dysplasia, no sweat glands; 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. G6PD alleles; Patches of color blindness

Descent of cells: How mosaics are made. Events during development. 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/CalicoCatBody.gif.jpe

Molecular basis of Barr body formation 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.

Occurs in a “window” of time during development http://bioweb.wku.edu/courses/biol566/Images/PlathF2.jpg

Active and inactive regions Red: active genes. Black: inactive Xic is responsible for this process; if moved to an autosome, that chromosome will be inactivated.

Polygenic Traits Polygenic traits: different from multiple genes Seems like it should be the same, but no Also called Quantitative traits Polygenic traits are different in AMOUNT not TYPE Range of heights vs. purple/white Traits studied by Mendel: “discrete” Polygenic traits usually show continuous variation Height, weight, eye color, etc. Number of phenotypic classes depends on how much you subdivide.

Polygenic Traits-2 Some polygenic traits are”meristic” Must be integers; meristic traits must be counted Number of kernels of corn can’t be continuous Offspring of crosses appear blended Still fit into Mendel’s notion of unit factors Multiple genes, and their alleles, are additive or not The total number of additive alleles determines the phenotype. Usually studied using statistics Distribution of traits follows bell curve Mean, standard deviation, and variance

Quantitative traits are Mendelian Example: red and white wheat. Red results from an additive allele, “white” is the absence of of additive alleles. When the F1 plants are crossed, an apparently continuous range of phenotypes is produced. Including a “white” which is 1/16 of total. Closer view: 1:4:6:4:1

Five phenotypic classes: AB Ab aB ab AABB AABb AaBB AaBb Aabb aaBb aaBB aabb Five phenotypic classes: 4+ alleles, 3+ alleles, 2+ alleles, 1+ allele, none

Summary of polygenic idea

Continuous variation Traits usually quantifiable (weighing, etc.) Two or more genes contribute to phenotype in an additive way. Individual allele either adds to phenotype or doesn’t Effect of each allele is small (but adds up) Lots of incremental effects create wide range of phenotypic variation, Study requires large numbers of individuals

Continuous variation-2 Variation appears continuous because these traits often affected by the environment. note bell curve.