Unit 5 Beta

Heredity: the one-page sheet

5.1 Meiosis

Meiosis makes haploid gametes from a diploid cell. The DNA is copied once, in S phase, and then the cell divides twice. In meiosis I, homologous chromosomes pair, line up side by side across the middle and separate to opposite poles, so each of the two cells is haploid but its chromosomes still have two sister chromatids. In meiosis II, with no further copying, the chromosomes line up singly and their sister chromatids separate, giving four haploid cells. Fertilization of a haploid egg by a haploid sperm restores the diploid number. Mitosis keeps the chromosome number and makes identical cells; meiosis halves it and makes cells that differ.

Diploid cells (2n) hold two sets of chromosomes, one from each parent; haploid cells (n) hold one set. In humans 2n = 46 and n = 23.
Homologous chromosomes carry the same genes in the same order but may carry different alleles (versions of a gene). Sister chromatids are identical copies; homologs are not.
Meiosis is one round of DNA copying followed by two divisions. Meiosis I separates homologs and halves the chromosome number; meiosis II separates sister chromatids.
Meiosis makes four haploid gametes (or spores) that differ from each other; mitosis makes two diploid cells identical to the parent.
Fertilization restores the diploid number, so in sexual reproduction meiosis and fertilization alternate every generation.

Every chromosome is two identical sister chromatids, and the cell is still diploid: each kind of chromosome is present twice, one homolog from each parent. The cell now holds its chromosomes as pairs, each pair four chromatids thick. One homolog of every pair faces each pole. Two cells form, each haploid: one chromosome of each kind, each still made of two sister chromatids. Four haploid cells form from the one diploid cell, each with half the parent's chromosome number. The zygote is diploid again, with one set of chromosomes from each parent, so the chromosome number stays the same from one generation to the next.

gamete: A sex cell: a sperm cell or an egg cell. Gametes are haploid, carrying one chromosome of each kind, and two of them join at fertilization to start a new individual.
haploid: Having one set of chromosomes: one of each kind, written n. Human gametes are haploid, with n = 23.
diploid: Having two sets of chromosomes, one set from each parent, so every kind of chromosome is present as a homologous pair; written 2n. Human body cells are diploid, with 2n = 46.
chromosome number: The number of chromosomes in a cell, counted by centromeres. A species' diploid number (2n) is in its body cells and its haploid number (n) in its gametes; humans have 2n = 46 and n = 23.
allele: One of the different versions of the same gene. The two chromosomes of a homologous pair carry the same genes in the same order, but may carry different alleles of them. (Topic 5.3 covers how alleles act.)
homologous chromosomes: The two chromosomes of a pair in a diploid cell, one inherited from each parent. They have the same length, centromere position and genes in the same order, but may carry different alleles. Not to be confused with sister chromatids, which are identical copies.
sex chromosome: A chromosome that differs between the sexes and helps set an individual's sex; in humans the X and Y chromosomes (females XX, males XY). All other chromosomes are autosomes: humans have 22 pairs of autosomes and one pair of sex chromosomes.
karyotype: A picture of all the chromosomes of one cell, photographed during division and arranged in homologous pairs by size and centromere position, with the sex chromosomes last. Used to count chromosomes and spot large changes.
meiosis: The two-step cell division that makes haploid gametes (or spores) from a diploid cell: DNA is copied once, then the cell divides twice, giving four haploid cells that differ from one another.
meiosis I: The first division of meiosis. Homologous chromosomes pair, line up side by side at the middle of the cell and are pulled to opposite poles, so each of the two new cells is haploid, with every chromosome still made of two sister chromatids.
synapsis: The pairing of homologous chromosomes, gene by gene along their length, early in meiosis I. The paired homologs (four chromatids in all) are called a tetrad or bivalent.
meiosis II: The second division of meiosis, with no DNA copying before it. In each haploid cell the chromosomes line up singly and their sister chromatids separate, as in mitosis, giving four haploid cells in all.
fertilization: The joining of a haploid sperm and a haploid egg to form a diploid zygote, the first cell of a new individual, with one set of chromosomes from each parent.
sexual reproduction: Reproduction in which two parents each give a haploid gamete, made by meiosis, and the gametes join at fertilization. The offspring differ from each parent and from one another.
meiosis versus mitosis: The comparison between the two divisions: mitosis is one division making two diploid cells identical to the parent (growth, repair, asexual reproduction); meiosis is two divisions making four haploid cells that differ from the parent and from each other (gametes).

5.2 Meiosis and Genetic Diversity

Meiosis and fertilization make every offspring genetically new. In prophase I, crossing over swaps pieces between homologs and makes recombinant chromosomes. At metaphase I, each homologous pair lines up independently, so gametes get random mixes of maternal and paternal chromosomes (2ⁿ combinations). Random fertilization then joins any sperm with any egg. When chromosomes fail to separate (nondisjunction), gametes carry an extra or a missing chromosome: an error in meiosis I affects all four gametes, an error in meiosis II two of them. Fertilization of such a gamete gives trisomy or monosomy, as in Down syndrome (trisomy 21), Turner syndrome (45,X) and Klinefelter syndrome (47,XXY).

Crossing over in prophase I swaps pieces between homologs, making recombinant chromosomes with new combinations of alleles.
Independent assortment: each homologous pair lines up at metaphase I independently, giving 2ⁿ chromosome combinations (2²³ ≈ 8.4 million in humans).
Random fertilization multiplies the mother's and father's possibilities, so every offspring is new. Together these three make the genetic variation of sexual reproduction.
Nondisjunction in meiosis I makes all four gametes abnormal (two n + 1, two n − 1); in meiosis II, two of the four (one n + 1, one n − 1).
Fertilization of an abnormal gamete gives aneuploidy: trisomy (2n + 1) or monosomy (2n − 1). Examples: Down syndrome (trisomy 21), Turner syndrome (45,X), Klinefelter syndrome (47,XXY).

Some chromatids now carry recombinant combinations of alleles, mixing the mother's and the father's versions on one chromosome. Each gamete receives a random mix of maternal and paternal chromosomes: 2ⁿ possible combinations, about 8.4 million in humans. Each zygote is a new combination, about 70 trillion possibilities per couple before crossing over is counted, so siblings differ. Some gametes get an extra copy of that chromosome (n + 1) and some get none (n − 1). The zygote has three copies (trisomy) or one copy (monosomy) of that chromosome in every cell, which changes development; trisomy 21 causes Down syndrome.

crossing over: The exchange of matching pieces between a chromatid of one homolog and a chromatid of the other, while homologous chromosomes are paired in prophase I. The places where the chromatids cross and swap are visible as chiasmata (singular chiasma).
recombinant chromosome: A chromosome (or chromatid, or gamete) that carries a new combination of alleles, made by crossing over, that was not on either of the parent's homologs. Genetic recombination is the making of such new combinations.
independent assortment: The random, independent way each homologous pair lines up at metaphase I: which homolog of one pair goes to a given pole does not affect which homolog of another pair goes there. With n pairs, it gives 2ⁿ possible chromosome combinations in gametes (about 8.4 million for humans).
random fertilization: The chance joining of any one of a father's genetically different sperm with any one of a mother's genetically different eggs, which multiplies the number of possible offspring combinations (about 70 trillion for one human couple, before counting crossing over).
genetic variation: Differences in DNA, and so in alleles and their combinations, among individuals. In sexual reproduction, crossing over, independent assortment and random fertilization make each offspring's combination new.
nondisjunction: The failure of chromosomes to separate correctly in meiosis: a homologous pair in meiosis I, or two sister chromatids in meiosis II. It gives gametes with an extra chromosome (n + 1) or a missing one (n − 1).
aneuploidy: Having an abnormal number of one or more chromosomes, usually after nondisjunction: trisomy is three copies of a chromosome (2n + 1), monosomy one copy (2n − 1).
Down syndrome: A condition caused, in most cases, by trisomy 21: three copies of chromosome 21 in every cell, usually from nondisjunction in the egg. Its likelihood rises with the mother's age. It affects development, including learning and heart formation.
Turner syndrome: Aneuploidy of the sex chromosomes, such as Turner syndrome (45,X: a single X and no second sex chromosome, in a female) and Klinefelter syndrome (47,XXY, in a male). Effects are milder than for most autosome changes.

5.3 Mendelian Genetics

Each diploid organism carries two alleles of every gene, one on each homolog. Its genotype may be homozygous or heterozygous; a dominant allele sets the phenotype of a heterozygote, and a recessive allele shows only in a homozygote. Because homologs separate in meiosis I, each gamete gets one allele of each gene (segregation), and genes on different chromosome pairs sort independently (independent assortment). Punnett squares and the product and sum rules predict 3:1 and 1:2:1 monohybrid ratios, 9:3:3:1 dihybrid ratios and the 1:1 result of a testcross on a heterozygote. Pedigrees reveal autosomal recessive, autosomal dominant and X-linked patterns; X-linked recessive traits are more common in males, who have one X. The same rules apply across eukaryotes, which is evidence of common ancestry.

Genotype is the pair of alleles (PP, Pp, pp); phenotype is the trait you see. A dominant allele shows in a heterozygote; a recessive one shows only when there are two copies.
Law of segregation: the two alleles of a gene separate into different gametes, because homologs separate in meiosis I. Law of independent assortment: genes on different chromosome pairs sort independently.
Punnett squares and the product rule (multiply chances of independent events) and sum rule (add chances of mutually exclusive outcomes) predict ratios: 3:1 and 1:2:1 for a monohybrid cross, 9:3:3:1 for a dihybrid cross.
A testcross to a homozygous recessive reveals an unknown genotype: any recessive offspring means the parent is heterozygous.
Pedigrees show the pattern: autosomal recessive (skips generations, carriers), autosomal dominant (every generation), X-linked recessive (mostly males, passed through carrier daughters). The same rules in peas, flies and people point to common ancestry.

Its genotype can be homozygous (two identical alleles) or heterozygous (two different ones). A Pp plant looks like a PP plant, and the recessive allele is hidden. Each gamete carries one allele of each gene, and a heterozygote makes P and p gametes in equal numbers: the law of segregation. Pp × Pp gives PP, Pp and pp offspring in a 1:2:1 ratio, so 3 show the dominant phenotype for every 1 recessive. AaBb makes AB, Ab, aB and ab gametes equally (independent assortment), and AaBb × AaBb gives a 9:3:3:1 phenotype ratio. A male shows whatever allele his one X carries, so X-linked recessive traits are far more common in males.

sex-linked: Describes a gene on a sex chromosome. Most are X-linked: on the X but not the Y. A male has one X, so he is hemizygous for X-linked genes, and a single recessive allele shows in him. Y-linked genes pass only from father to son.
Gregor Mendel: Gregor Mendel (1822-1884), who worked out the basic rules of inheritance by crossing true-breeding pea plants (plants that always produce offspring like themselves) and counting the traits of their hybrid offspring over several generations.
genotype: The alleles an individual has for a gene, written with letters (for example PP, Pp or pp). Two identical alleles make an individual homozygous (a homozygote); two different alleles make it heterozygous (a heterozygote).
phenotype: The observable or measurable traits of an individual, such as flower color, height or the presence of a condition, which result from its genotype (and, topic 5.5 adds, its environment).
dominant allele: A dominant allele sets the phenotype even when only one copy is present (in a heterozygote); a recessive allele shows in the phenotype only when two copies are present. Dominant alleles are written with a capital letter, recessive with a lowercase one.
P generation: The labels for generations in a cross: P (parental) for the original true-breeding parents, F1 (first filial) for their offspring, and F2 for the offspring of F1 individuals crossed with each other or self-fertilized.
law of segregation: Mendel's law of segregation: the two alleles of a gene separate from each other when gametes form, so each gamete carries just one allele of each gene. Its physical basis is the separation of homologous chromosomes in meiosis I.
law of independent assortment: Mendel's law of independent assortment: alleles of genes on different chromosome pairs go into gametes independently of each other, because each homologous pair lines up independently at metaphase I.
Punnett square: A grid used to predict the offspring of a cross: one parent's possible gametes are written along the top, the other's down the side, and each box combines one of each, giving the expected proportions of genotypes and phenotypes.
monohybrid cross: A cross that follows one gene, usually between two heterozygotes (Aa × Aa). With complete dominance it gives a 3:1 phenotype ratio and a 1:2:1 genotype ratio (AA : Aa : aa).
dihybrid cross: A cross that follows two genes at once, usually between two double heterozygotes (AaBb × AaBb). If the genes are on different chromosome pairs, it gives a 9:3:3:1 phenotype ratio.
testcross: A cross of an individual with the dominant phenotype but unknown genotype to a homozygous recessive individual. If any offspring show the recessive phenotype, the tested individual is heterozygous; a heterozygote gives a 1:1 ratio.
product rule: The two rules for combining probabilities in genetics. Product rule (multiplication rule): the chance that independent events all happen is the product of their chances. Sum rule (addition rule): the chance that one of several mutually exclusive outcomes happens is the sum of their chances.
pedigree: A family tree that shows which members have a trait: squares for males, circles for females, filled symbols for affected people, lines for matings and children, and Roman numerals for generations. Used to work out how a trait is inherited.
autosomal recessive: Inheritance of a gene on an autosome, so both sexes are affected equally. An autosomal recessive trait can appear in children of two unaffected carriers (heterozygotes); an autosomal dominant trait appears in every generation, and an affected person usually has an affected parent.
cystic fibrosis: Human conditions with simple inheritance: cystic fibrosis and Tay-Sachs disease (autosomal recessive) and Huntington's disease (autosomal dominant, with symptoms that usually begin in adulthood).
shared genetic mechanisms: The same mechanisms of inheritance (DNA, chromosomes, meiosis, segregation of alleles) work in plants, animals and fungi alike, which is evidence that these organisms share common ancestry.

5.4 Non-Mendelian Genetics

Mendel's ratios assume genes on different chromosome pairs, one dominant and one recessive allele, one gene per trait and nuclear genes. When genes are linked, close on one chromosome, parental combinations outnumber recombinants; the recombination frequency (recombinants ÷ total × 100) measures their distance in map units and gives gene order. Incomplete dominance gives an in-between heterozygote and codominance shows both alleles, as in ABO blood types, a gene with multiple alleles. Polygenic traits vary continuously, pleiotropic genes affect several traits, and epistasis lets one gene mask another. Mitochondrial and chloroplast genes are usually inherited from the mother, so reciprocal crosses differ. A chi-square test compares observed counts with those expected under a hypothesis.

Linked genes are close together on one chromosome and tend to be inherited together. Recombination frequency = recombinants ÷ total × 100; 1% = 1 map unit. Values near 50% look like unlinked genes. Frequencies give gene order on a linkage map.
Incomplete dominance: the heterozygote is in between (pink snapdragons). Codominance: both alleles show fully (AB blood type, roan cattle). The ABO gene has multiple alleles.
Polygenic traits (height, skin color) depend on many genes and show continuous variation. Pleiotropy: one gene, many traits. Epistasis: one gene masks another.
Nonnuclear inheritance: mitochondrial and chloroplast genes come from one parent, usually the mother. Sex-linked and cytoplasmic traits give different results in a reciprocal cross.
Compare the observed ratio with the expected ratio using a chi-square test before claiming a cross does or does not fit Mendel.

When two genes sit close together on one chromosome (linked genes), their alleles go into gametes together and that assumption fails. Parental-type offspring far outnumber the other classes, instead of the 1:1:1:1 that independent assortment predicts. A few gametes carry recombinant combinations (B p, b P), and their share, the recombination frequency, rises with the distance between the genes: 1% = 1 map unit. Crosses give other ratios: 1:2:1 phenotypes with incomplete dominance or codominance, continuous variation for polygenic traits, 9:3:4 with epistasis. Their traits are inherited from the mother, so reciprocal crosses give different results. A large χ² (above the critical value) rejects the hypothesis, for example independent assortment for linked genes.

reciprocal cross: A pair of crosses in which the phenotypes of the mother and father are swapped (female A × male B, then female B × male A). Different results show that the trait is sex-linked or inherited through one parent's cytoplasm.
linked genes: Genes close together on the same chromosome, which tend to be inherited together because they go into gametes on the same chromosome. They do not assort independently, so crosses give too many parental-type offspring for Mendel's ratios.
recombination frequency: The percentage of offspring with recombinant (nonparental) combinations of alleles: recombinants ÷ total × 100. It rises with the distance between two genes, so it is used to build a linkage map; 1% recombination is 1 map unit (centimorgan). Values near 50% look like unlinked genes.
incomplete dominance: A pattern in which a heterozygote has a phenotype in between those of the two homozygotes, such as pink snapdragons from red and white parents. A cross of two heterozygotes gives a 1:2:1 phenotype ratio.
codominance: A pattern in which a heterozygote shows the full effects of both alleles, such as AB blood, where red cells carry both A and B markers, or roan cattle with red and white hairs. A gene with more than two alleles in a population, such as the ABO gene (Iᴬ, Iᴮ, i), has multiple alleles.
polygenic inheritance: Describes a trait affected by many genes, each adding a small effect, such as human height or skin color. Polygenic traits show continuous variation: a smooth range of values, often bell-shaped, rather than a few distinct classes.
pleiotropy: One gene affecting several different traits. For example, the gene altered in cystic fibrosis affects the lungs, the digestive system, sweat and fertility, because its protein works in many tissues.
epistasis: An interaction in which one gene's alleles mask or change the effect of another gene. In Labrador retrievers, a dog with ee cannot put dark pigment in its hair, so it is yellow whatever its alleles for black or brown; crosses of double heterozygotes give 9:3:4 instead of 9:3:3:1.
nonnuclear inheritance: Inheritance of genes in mitochondria and chloroplasts, which are passed on in the cytoplasm of the egg. Offspring usually inherit them from one parent (in humans, the mother), so these traits do not follow Mendel's rules.
expected ratio: The ratio of offspring classes predicted by a hypothesis, such as 3:1 or 9:3:3:1, compared with the observed ratio actually counted. A chi-square test asks whether the difference is small enough to be chance.

5.5 Environmental Effects on Phenotype

A phenotype comes from the genotype acting in an environment. Phenotypic plasticity is the ability of one genotype to give different phenotypes in different conditions; its norm of reaction is the range across environments. Hydrangeas bloom blue in acidic soil, where aluminum is taken up and binds the pigment, and pink in neutral soil. Many turtles' sex depends on incubation temperature. Himalayan rabbits and Siamese cats grow dark fur only on cool body parts, because their pigment enzyme works only when cool. Nutrition affects height, and a low-phenylalanine diet prevents the effects of PKU. Most traits are multifactorial. Such environmental changes alter the phenotype, not the alleles passed to offspring.

Phenotypic plasticity: one genotype can produce different phenotypes in different environments. The range it produces across environments is its norm of reaction.
Examples: hydrangea flower color set by soil pH (via aluminum), temperature-dependent sex determination in turtles, temperature-sensitive fur color in Himalayan rabbits and Siamese cats.
In humans, nutrition affects height, and diet controls the effects of phenylketonuria (PKU).
Most traits are multifactorial: many genes plus environment. The genotype sets the possible range; the environment decides where in it an individual lands.
Environmentally caused changes are not passed on through the genes: a blue hydrangea's seeds carry the same alleles as a pink one's.

The same genotype can give a different phenotype when those conditions change (phenotypic plasticity). Aluminum binds the flower pigment and turns it blue; in neutral soil, with little aluminum taken up, the same plant blooms pink. Dark fur grows only where the skin is cooler: ears, nose, paws and tail. Warm nests give mostly females and cool nests mostly males, with no sex chromosomes involved. With the diet from birth, the brain develops normally: the genotype is unchanged, but the phenotype is not the one the genotype alone predicts.

phenotypic plasticity: The ability of one genotype to produce different phenotypes in different environments. The range of phenotypes a genotype produces across a range of environments is its norm of reaction.
hydrangea flower color: A textbook case of the environment changing phenotype: in many hydrangeas, acidic soil (low soil pH) makes aluminum available, the plant takes it up and it binds the flower pigment, giving blue flowers; in neutral or alkaline soil the same plant has pink flowers.
temperature-dependent sex determination: A system in which the temperature of the eggs during a sensitive period of incubation, not sex chromosomes, decides whether an embryo becomes male or female. In many turtles, warm nests give mostly females and cool nests mostly males.
temperature-sensitive fur color: Coat color in Himalayan rabbits and Siamese cats: their pigment-making enzyme works only at cooler temperatures, so dark fur grows on the cooler ears, nose, paws and tail, and light fur on the warmer body.
nutrition and height: The effect of diet on height, a polygenic trait: people with the same genes for height grow taller with better nutrition in childhood, which is why average height in many countries rose over the past century.
phenylketonuria: Phenylketonuria (PKU), an autosomal recessive condition in which an enzyme that breaks down the amino acid phenylalanine does not work. Phenylalanine builds up and harms the developing brain unless the child eats a low-phenylalanine diet from birth; with the diet, development is typically normal.
multifactorial trait: A trait shaped by several genes together with environmental factors, such as height, many heart conditions or type 2 diabetes. Such gene-environment interaction means the genotype sets a range of possible phenotypes and the environment decides where in the range an individual falls.