Genetics 24231 Faculty of Agriculture

1. Genetics 24231Faculty of Agriculture Instructor: Dr. Jihad Abdallah Topic 10: Non-Mendelian inheritance

2. NON-MENDELIAN INHERITANCE • Many genes do not follow a Mendelian inheritance pattern • e.g., Closely linked genes do not follow Mendel’s law of independent assortment • This chapter will discuss additional and more non-Mendelian inheritance patterns • Maternal effect • Epigenetic inheritance • Extranuclear inheritance

3. MATERNAL EFFECT • Inheritance pattern for certain nuclear genes in which the genotype of the mother directly determines the phenotype of her offspring • For maternal effect genes, the genotypes of the father and the offspring do not affect the phenotype of offspring • Explained by the accumulation of gene products the mother provides to her developing eggs

4. The genotype of the mother determines the phenotype of the offspring for maternal effect genes A. E. Boycott (1920s) • First to study an example of maternal effect • Involved morphological features of water snail • Limnea peregra • Shell and internal organs can be either right-handed (Dextral) or left-handed (sinistral) • Determined by cleavage pattern of egg after fertilization • Dextral orientation is more common and dominant

5. Boycott began with two different true-breeding strains • One dextral, one sinistral • Dextral ♀ x sinistral ♂  dextral offspring • Reciprocal cross  sinistral offspring • Contradict a Mendelian pattern of inheritance Dextral female Sinistral male Sinistral female Dextral male All sinistral All dextral

6. Sturtevant(1923) • Sturtevant(1923) proposed that Boycott’s results could be explained by a maternal effect gene • Conclusions drawn from F2 and F3 generations • Dextral (D) is dominant to sinistral (d) • Phenotype of offspring is determined by genotype of mother

8. Female gametes receive gene products from the mother that affect early development stages of the embryo • Oogenesis in female animals • Oocyte is formed • Nourished by surrounding diploid maternal nurse cells • Receives gene products from nurse cells • Genotype of nurse cells determines gene products in oocyte

10. EPIGENETIC INHERITANCE • Modification occurs to a nuclear gene or chromosome that alters gene expression. • Occur during spermatogenesis, oogenesis, and early stages of embryogenesis • Gene expression is altered • May be fixed during an individual’s lifetime • Expression is not permanently changed over multiple generations • DNA sequence is not altered • When the individual makes gametes, the genes may become activated and remain operative in the offspring which receives it.

11. Two types of epigenetic inheritance will be discussed: • Dosage compensation • Genomic imprinting

12. DOSAGE COMPENSATION • Males and females of many species have different numbers of certain sex chromosomes (e.g., X chromosomes) • But the level of expression of many genes on sex chromosomes is similar in both sexes • In mammals, it is initiated during early stages of development

13. Most X-linked genes show dosage compensation • Some X-linked genes do not • Reasons for the difference are not understood

14. Apricot eye color in Drosophila • Conferred by an X-linked gene • Homozygous females resemble males (two copies of the allele in a female produce a phenotype similar to one copy in a male) • Females heterozygous for the apricot allele have paler eye color

15. Dosage compensation does not occur for all eye color alleles in Drosophila • e.g., Eosin eye color • Conferred by an X-linked gene • Homozygous eosin females have darker eye color than hemizygous eosin males • Dark eosin and light eosin • Females heterozygous for the eosin allele and the white allele have light eosin eye color • Two copies of the allele in a female produce a phenotype different than one copy in a male

17. Murray Barr and Ewart Bertram (1949) • Identified a highly condensed structure in interphase nuclei of somatic cells of female cats • This structure was absent in male cats • “Barr body” • Later identified as a highly condensed X chromosome

18. X chromosome inactivation • DNA in inactivated X chromosomes becomes highly compacted • A Barr body is formed • Most genes cannot be expressed

19. XX females  1 Barr body • XY males  0 Barr bodies • XO females  0 Barr bodies (Turner syndrome) • XXX females  2 Barr bodies (Triple X syndrome) • XXY males  1 Barr body (Kleinfelter syndrome)

20. Genomic imprinting • Occurs during gamete formation (before fertilization) • Involves a single gene or chromosome • Governs whether offspring express maternally- or paternally-derived gene

21. Genomic imprinting • Genomic imprinting involves the physical marking of a segment of DNA • Mark is retained and recognized throughout the life of the organism inheriting the marked DNA • Resulting phenotypes display non-Mendelian inheritance patterns • Offspring expresses one allele, not both • “Monoallelic expression”

22. Genomic imprinting in mice • The Igf-2 gene encodes an insulin-like growth factor • Functional allele required for normal size • Igf-2m allele encodes a non-functional protein • Imprinting results in the expression of the paternal allele only • Paternal allele is transcribed • Maternal allele is not transcribed (transcriptionally silent)

23. The Igf-2 gene encodes an insulin-like growth factor • Functional allele required for normal size • Igf-2m allele encodes a non-functional protein • Igf-2m Igf-2m♀ x Igf-2 Igf-2♂ Normal offspring • Igf-2m Igf-2m♂ x Igf-2 Igf-2♀ Dwarf offspring • Different results in reciprocal crosses generally indicate sex-linked traits but in this case, it indicates genomic imprinting of autosomal alleles

24. The imprint of the Igf-2 gene is erased during gametogenesis • A new imprint is then established • Oocytes possess an imprinted gene that is silenced • Sperm possess a gene that is not silenced • The phenotypes of offspring are determined by the paternally derived allele

25. Genomic imprinting • Involves differentially methylated regions (DMRs) located near imprinted genes • Maternal or paternal copy is methylated, not both • Methylation generally inhibits expression • Can enhance binding of transcription-inhibiting proteins and/or inhibit binding of transcription-enhancing proteins

27. Methylation occurs during gametogenesis • Methylated in oocyte or sperm, not both • Imprinting is maintained in the somatic cells of the offspring • Imprinting is erased during gametogenesis in these offspring • New imprinting established

29. EXTRANUCLEAR INHERITANCE • Most genes are found in the cell’s nucleus • Some genes are found outside of the nucleus • Some organelles possess genetic material • Resulting phenotypes display non-Mendelian inheritance patterns • “Extranuclear inheritance” • “Cytoplasmic inheritance”

30. Mitochondria and chloroplasts possess DNA • Circular chromosomes resemble smaller versions of bacterial chromosomes • Located in the nucleoid region of the organelles • Multiple nucleoids often present • Each can contain multiple copies of the chromosome

32. Mitochondrial genome size varies greatly among different species • 400-fold variation in mitochondrial chromosome size • Mitochondrial genomes of animals tend to be fairly small • Mitochondrial genomes of fungi, algae, and protists tend to be intermediate in size • Mitochondrial genomes of plants tend to be fairly large

33. Human mitochondrial DNA is called mtDNA • Circular chromosome 17,000 base pairs in length • Less than 1% of a typical bacterial chromosome • Carries relatively few genes • Genes encoding rRNA and tRNA • 13 genes encoding proteins functioning in ATP generation via oxidative phosphorylation

34. Chloroplast genomes tend to be larger than mitochondrial genomes • Correspondingly greater number of genes • ~100,000 – 200,000 bp in length • Ten times larger than the mitochondrial genome of animal cells

35. The inheritance pattern of extranuclear genetic material displays non-Mendelian inheritance • Mitochondria and plastids do not segregate into gametes as do nuclear chromosomes

36. Pigmentation in Mirabilis jalapa • The four-o’clock plant • Pigmentation is determined by chloroplast genes • Green phenotype is the wild-type condition • Green pigment is formed • White phenotype is due to a mutation in a chloroplast gene • Synthesis of green pigment is diminished • Cells containing both types of chloroplasts “Heteroplasmy” display green coloration because the normal chloroplasts produce the green pigment

37. Pigmentation in Mirabilis jalapa • Pigmentation in the offspring depends solely on the maternal parent • “Maternal inheritance” • Chloroplasts are inherited only through the cytoplasm of the egg

40. Symbiosis involves a close relationship between two species where at least one member benefits • Endosymbiosis involves such a relationship where one organism lives inside the other • Mitochondria and chloroplasts were once free-living bacteria • Engulfed and retained by early eukaryotes (Endosymbiosis)