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10/19/15 Simple Mendelian inheritance describes inheritance patterns that obey • The Law of Segregation • The Law of Independent Assortment As well as two other rules: • Genes are passed unaltered from generation to generation (except for rare mutations) • Expression of the genes in the offspring directly influences their traits Chapter 06 Lecture Outline Some genes violate these rules, and deviate from the expectations of simple Mendelian inheritance Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 2 1 • In this lecture we will discuss inheritance patterns that do not conform to Mendelian predictions o Extranuclear inheritance • Genes not in nucleus o Mitochondria o Chloroplasts • These became part of the cell by endosymbiosis o Epigenetic inheritance and imprinting • Genes are altered in the offspring (ex: methylation) o Maternal effect • Gene expression in the mother determines traits of offspring Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 3 Extranuclear Inheritance Shell coiling in the water snail Lymnaea is due to maternal effect inheritance Chloroplast Genome • Extranuclear inheritance - Traits are inherited through genes that are not in the nucleus, but are in other organelles o Also known as cytoplasmic inheritance • The chromosome of both mitochondria and chloroplasts is composed of a single circular double-stranded DNA • Like bacteria, the chromosomes of mitochondria and chloroplasts are found in nucleoids • The two most important examples are genes in o Mitochondria o Chloroplasts o The nucleoid may contain many copies of the one chromosome o There may also be multiple nucleoids nucleoid Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 4 5 nucleoid Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 6 1 10/19/15 6.2 Extranuclear Inheritance: } Extranuclear genes display non-Mendelian inheritance, which has four characteristics: Mitochondria q q q General features of mitochondrial genomes Predicting the outcome of crosses involving genetic variation in mitochondrial genomes How mutations in mitochondrial genes cause human diseases Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display ◦ Typical Mendelian ratios do not occur, because meiosisbased segregation is not involved. ◦ Reciprocal crosses usually show uniparental inheritance. All progeny have the phenotype of one parent, generally the mother because the zygote receives nearly all of its cytoplasm (including organelles) from the ovum. ◦ Extranuclear genes cannot be mapped to chromosomes in the nucleus. ◦ If a nucleus with a different genotype is substituted, nonMendelian inheritance is unaffected. 7 8 • The main function of mitochondria o oxidative phosphorylation - produces ATP o ATP used as an energy source to drive cellular reactions Mitochondria Genome • Like chloroplasts, mitochondria contain a single circular chromosome • The genetic material in mitochondria is referred to as mtDNA o Contained within the nucleoid o Multiple copies of the single chromosome • Human mtDNA o 17,000 bp o Relatively few genes o rRNA and tRNA genes o 13 genes that function in oxidative phosphorylation • Most mitochondrial proteins are encoded by genes in the nucleus o Proteins made in cytoplasm but have a signal to direct them to mitochondria Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 9 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 10 Ribosomal RNA genes Necessary for synthesis of mitochondrial proteins Transfer RNA genes Mitochondrial Inheritance NADH dehydrogenase subunit genes (7) Cytochrome b gene Cytochrome c oxidase subunit genes (3) Function in oxidative phosphorylation • Like chloroplasts, mitochondria are usually – but not always – inherited from the female parent via egg cells ATP synthase subunit genes (2) Noncoding DNA Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. tRNAPhe tRNAPro 12S rRNA tRNAVal tRNAThr tRNAGlu 16S rRNA tRNALeu tRNAIle tRNAGln tRNAMet tRNALeu tRNASer tRNAHis tRNATrp tRNAAla tRNAAsn tRNAArg tRNACys tRNATyr tRNAGly tRNASer tRNAAsp tRNALys Figure 6.5 11 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 12 2 10/19/15 Human Mitochondrial Diseases • Species with maternal inheritance may, on occasion, exhibit paternal leakage o Mitochondria provided through the sperm o Example: In the mouse • Two mechanisms of mitochondrial disease: 1. Transmitted from mother to offspring via the egg • Follow a strict maternal inheritance pattern 2. Mutations can occur in somatic cells during aging • 1-4 paternal mitochondria are inherited for every 100,000 maternal mitochondria per generation of offspring • Mitochondria are especially susceptible to DNA damage from free radicals • Over 200 human mitochondrial diseases discovered o Typically chronic degenerative disorders affecting cells that need high levels of ATP • Nerve and muscle cells Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 13 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 14 • Example: Leber’s hereditary optic neuropathy (LHON) o Affects the optic nerve o May lead to progressive loss of vision in one or both eyes o LHON is caused by mutations in several different mitochondrial genes • Kearns-Sayre syndrome (OMIM 530000) produces three types of neuromuscular defects: o Progressive paralysis of certain eye muscles. o Abnormal pigment accumulation on the retina, causing chronic inflammation and degeneration of the retina. o Heart disease. 15 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 16 Maternal Effect Inheritance • Maternal effect – Only the genotype of the mother controls phenotype of offspring o Genotype of father has no effect o Genotype of offspring has no effect o Controlled by nuclear genes 6.5 Maternal Effect q q q Definition of maternal effect Predicting the outcome of crosses for genes that exhibit a maternal effect pattern of inheritance • Phenomenon is due to the accumulation of gene products that the mother provides to her developing eggs The molecular mechanism of maternal effect inheritance Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 18 3 10/19/15 • Example: Coiling in the snail, Lymnaea • The first example of a maternal effect gene • Discovered in the 1920s by Arthur Boycott Reciprocal cross Parental generation DD • Two different directions in which F the shell and internal organs can twist 1 • Right-handed (dextral) - more common and dominant • Left-handed (sinistral) x dd DD generation x Dd All dextral Dd All sinistral F2 generation • Reciprocal crosses and crosses of the of the F1s demonstrated a non-Mendelian pattern of F inheritance 3 • Alfred Sturtevant proposed that coiling is controlled by a maternal effect gene • Phenotypes controlled by the genotype of the mother • Not the genotype of father or offspring x dd Males and females 1 DD : 2 Dd : 1 dd All dextral Cross to each other generation Males and females • Even though twist is controlled by a nuclear gene 3 dextral : 1 sinistral 19 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Reciprocal cross x DD dd DD F1 generation – Maturing animal oocytes are surrounded by maternal cells that provide them with nutrients – These nurse cells are diploid, whereas the oocyte becomes haploid x Dd All dextral Dd All sinistral F1 mothers are Dd The dominant allele, D, caused ALL the F2 offspring to be dextral 20 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display • The non-Mendelian inheritance pattern of maternal effect genes can be explained by the process of oogenesis Parental generation x dd • He proposed one gene with two alleles D and d • Dd mothers produce dextral offspring even if the offspring are dd • dd mothers produce sinistral offspring even if the offspring are Dd Egg Nurse cells Dd Dd Dd Dd Dd Dd The nurse cells express mRNA and/or protein from genes of the d allele (red) and the D allele (green) and transfer those products to the egg. Dd F2 generation 1 DD : 2 Dd : 1 dd All dextral • In the example Males and females Cross to each other – A female Dd is heterozygous for the snail-coiling maternal effect gene – The haploid oocyte received just the d allele in meiosis F3 generation MalesFand females 2 mothers 3 with the D allele 1 with the d allele 3 dextral : 1 sinistral Explains this 3:1 ratio 21 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22 • Maternal effect genes encode RNA and proteins that play important roles in the early steps of embryogenesis – Example - cell division, cleavage pattern, body axis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mitotic spindle • Accumulation before fertilization allows development to proceed very quickly after fertilization Dextral • Therefore defective alleles in maternal effect genes tend to have a dramatic effect on the phenotype of the individual – In Drosophila, geneticists have identified several dozen maternal effect genes • Profound effects on the early stages of development Sinistral (c) An explanation of coiling direction at the cellular level Figure 6.11c 23 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 24 4 10/19/15 Extranuclear Inheritance • In many organisms, extranuclear genes inheritance is maternal. This differs from maternal effect in two ways: o Extranuclear inheritance is determined by genes in an organelle, while maternal effect derives from nuclear genes. o b. Extranuclear genotype matches individual’s phenotype, while in maternal effect the individual’s phenotype results from its mother’s genes. 25 5