Course: Genetics Faculty of Graduate Studies An-Najah National University NON-MENDELIAN INHERITANCE Dr. Heba Al-Fares

INTRODUCTION Mendelian inheritance patterns involve genes that Directly influence the outcome of an organism’s traits and Obey Mendel’s laws Most genes in eukaryotic species follow a Mendelian pattern of inheritance However, there are many that don’t Indeed, linkage which we considered in the last two lectures follows non-Mendelian inheritance

INTRODUCTION Additional patterns of inheritance that deviate from a Mendelian pattern include: Maternal effect and epigenetic inheritance Involve genes in the nucleus Extranuclear inheritance Involves genes in organelles other than the nucleus Mitochondria Chloroplasts

MATERNAL EFFECT Maternal effect refers to an inheritance pattern for certain nuclear genes in which the genotype of the mother directly determines the phenotype of her offspring Surprisingly, the genotypes of the father and offspring themselves do not affect the phenotype of the offspring This phenomenon is due to the accumulation of gene products that the mother provides to her developing eggs The phenotype of the progeny is determined by the mother’s genotype NOT phenotype The genotypes of the father and offspring do not affect the phenotype of the offspring

EPIGENETIC INHERITANCE Epigenetic inheritance refers to a pattern in which a modification occurs to a nuclear gene or chromosome that alters gene expression However, the expression is not permanently changed over the course of many generations Epigenetic changes are caused by DNA and chromosomal modifications These can occur during oogenesis, spermatogenesis or early embryonic development

Dosage Compensation The purpose of dosage compensation is to offset differences in the number of active sex chromosomes Dosage compensation has been studied extensively in mammals, Drosophila and Caenorhabditis elegans Depending on the species, dosage compensation occurs via different mechanisms

The mechanism of X inactivation, also known as the Lyon hypothesis, is schematically illustrated in Figure 7.4 The example involves a white and black variegated coat color found in certain strains of mice A female mouse has inherited two X chromosomes One from its mother that carries an allele conferring white coat color (Xb) One from its father that carries an allele conferring black coat color (XB) 7-20 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

While those from this will produce a patch of black fur The epithelial cells derived from this embryonic cell will produce a patch of white fur At an early stage of embryonic development While those from this will produce a patch of black fur Figure 7.4 7-21

During X chromosome inactivation, the DNA becomes highly compacted Most genes on the inactivated X cannot be expressed When this inactivated X is replicated during cell division Both copies remain highly compacted and inactive In a similar fashion, X inactivation is passed along to all future somatic cells Another example of variegated coat color Is found in calico cats Refer to Figure 7.3b 7-22 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Genomic Imprinting Genomic imprinting is a phenomenon in which expression of a gene depends on whether it is inherited from the male or the female parent Imprinted genes follow a non-Mendelian pattern of inheritance Depending on how the genes are “marked”, the offspring expresses either the maternally-inherited or the paternally-inherited allele Not both This is termed monoallelic expression 7-39 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Genomic imprinting is permanent in somatic cells However, the marking of alleles can be altered from generation to generation It may involve A single gene A part of a chromosome An entire chromosome Even all the chromosomes from one parent Imprinting is the reason that parthenogenesis ("virgin birth") does not occur in mammals. Two complete female genomes cannot produce viable young because of the imprinted genes. 7-44 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

7.3 EXTRANUCLEAR INHERITANCE Extranuclear inheritance refers to inheritance patterns involving genetic material outside the nucleus The two most important examples: mitochondria and chloroplasts These organelles are found in the cytoplasm Extranuclear inheritance = cytoplasmic inheritance 7-54 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

A nucleoid can contain more than one chromosome The genetic material of mitochondria and chloroplasts is located in a region called the nucleoid Refer to Figure 7.13 The genome is composed of a single circular chromosome containing double-stranded DNA Note: A nucleoid can contain more than one chromosome An organelle can contain more than one nucleoid Chloroplasts tend to have more nucleoids per organelle than mitochondria 7-55

There is a 400-fold variation in the size of mitochondrial genomes Besides variation in copy number, the sizes of organellar genomes also vary greatly among different species There is a 400-fold variation in the size of mitochondrial genomes There is also a substantial variation in size of chloroplast genomes In general, mitochondrial genomes are Fairly small in animals Intermediate in size in fungi, algae and protists Fairly large in plants 7-57 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

The main function of mitochondria is oxidative phosphorylation A process used to generate ATP (adenosine triphosphate) ATP is used as an energy source to drive cellular reactions The genetic material in mitochondria is referred to as mtDNA The human mtDNA consists of only 17,000 bp (Figure 7.14) It carries relatively few genes rRNA and tRNA genes 13 genes that function in oxidative phosphorylation Note: Most mitochondrial proteins are encoded by genes in the nucleus These proteins are made in the cytoplasm, then transported into the mitochondria 7-58 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

The main function of chloroplasts is photosynthesis The genetic material in chloroplasts is referred to as cpDNA It is typically about 10 times larger than the mitochondrial genome of animal cells The cpDNA of tobacco plant consists of 156,000 bp It carries between 110 and 120 different genes rRNA and tRNA genes Many genes that are required for photosynthesis As with mitochondria, many chloroplast proteins are encoded by genes in the nucleus These proteins contain chloroplast-targeting signals that direct them from the cytoplasm into the chloroplast 7-60 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Maternal Inheritance in the Four-o’clock Plant Carl Correns discovered that pigmentation in Mirabilis jalapa (the four o’clock plant) shows a non-Mendelian pattern of inheritance Leaves could be green, white or variegated (with both green and white sectors) Correns determined that the pigmentation of the offspring depended solely on the maternal parent and not at all on the paternal parent This is termed maternal inheritance Refer to Figure 7.16 7-62 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Figure 7.16 7-63 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Green phenotype is the wild-type White phenotype is the mutant In this example, maternal inheritance occurs because the chloroplasts are transmitted only through the cytoplasm of the egg The pollen grains do not transmit chloroplasts to the offspring The phenotype of leaves can be explained by the types of chloroplasts found in leaf cells Green phenotype is the wild-type Due to normal chloroplasts that can make green pigment White phenotype is the mutant Due to a mutation that prevents the synthesis of the green pigment A cell can contain both types of chloroplasts A condition termed heteroplasmy In this case, the leaf would be green 7-64 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Consider a fertilized egg that inherited two types of chloroplast Figure 7.17 provides a cellular explanation for the variegated phenotype in Mirabilis jalapa Consider a fertilized egg that inherited two types of chloroplast Green and white As the plant grows, the chloroplasts are irregularly distributed to daughter cells Sometimes, a cell may receive only white chloroplasts Such a cell will continue to divide and produce a white sector Cells that contain only green chloroplasts or a combination of green and white will ultimately produce green sectors 7-65 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Figure 7.17 7-66 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

The Pattern of Inheritance of Organelles The pattern of inheritance of mitochondria and chloroplasts varies among different species Heterogamous species Produce two kinds of gametes Female gamete  Large Provides most of the cytoplasm of the zygote Male gamete  Small Provides little more than a nucleus In these species, organelles are typically inherited from the mother 7-76 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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The Pattern of Inheritance of Organelles Species with maternal inheritance may, on occasion, exhibit paternal leakage The paternal parent provides mitochondria through the sperm In the mouse, for example, 1-4 paternal mitochondria are inherited for every 100,000 maternal mitochondria per generation of offspring 7-78 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Human Mitochondrial Diseases Human mtDNA is transmitted from mother to offspring via the cytoplasm of the egg Several human mitochondrial diseases have been discovered These are typically chronic degenerative disorders affecting the brain, heart, muscles, kidneys and endocrine glands Example: Leber’s hereditary optic neuropathy (LHON) Affects the optic nerve May lead to progressive loss of vision in one or both eyes LHON is caused by mutations in several different mitochondrial genes 7-79 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display