Lecture 15 Chromosome Variation & Errors BIOL 23373 Fall 2024 PDF

BIOL 23373 – General Genetics Fall 2024 Lecture 15 Chromosome Variation & Errors Announcements Bonus Quiz 5 (available after today’s class) is due before class on Monday, Sept. 30. Tutoring Tutoring @ the CORD offers 1-on-1 and small group assistance in ov...

BIOL 23373 – General Genetics Fall 2024 Lecture 15 Chromosome Variation & Errors Announcements Bonus Quiz 5 (available after today’s class) is due before class on Monday, Sept. 30. Tutoring Tutoring @ the CORD offers 1-on-1 and small group assistance in over 100 U of A courses. Students can meet with tutors in person or online by scheduling an appointment or accessing drop-in services. Learn more about Tutoring services and book an appointment at: https://success.uark.edu/academic-initia tives/tutoring.php Corresponding Readings Chapter sections: 8.1-8.8 Euploidy Number of chromosomes in a nucleus and the relative size and shape of each chromosome are species- specific characteristics. Cells are euploid when they have complete sets of chromosomes (e.g., n, 2n, 3n) Total number is an exact multiple of the number of chromosomes in one set Aneuploidy Cells are aneuploid if they contain a number of chromosomes that is not euploid (i.e., not an exact multiple of the number of chromosomes in one set) e.g., one chromosome too few or too many Aneuploidy is due to failed chromosome and sister chromatid segregation This is called chromosome nondisjunction and can result in abnormalities in chromosome number Chromosome Nondisjunction Chromosome nondisjunction is the failure of homologous chromosomes or sister chromatids to separate normally during cell division In somatic cells, it results in one daughter cell with an extra chromosome (2n1) and the other missing one chromosome (2n1) The relatively poor survival of these cells normally limits their number in animals, but some can result in cancer In germ-line cells, it results in aneuploid gametes that are either n1 or n1 7 Chromosome Nondisjunction 8 Nondisjunction in Germ-Line Cells Fusion of aneuploid gametes with normal (n) gametes produces trisomic (2n1) or monosomic (2n1) offspring Changes in gene dosage lead to an imbalance of gene products from the affected chromosome relative to the unaffected chromosomes 9 Gene Dosage & Balance Changes in gene dosage lead to an imbalance of gene products from the affected chromosome relative to the unaffected chromosomes Most animals are highly sensitive to changes in gene dosage In contrast, plants tolerate gene dosage changes more readily 10 Aneuploidy in Humans Humans are very sensitive to gene dosage changes and aneuploids usually do not survive Only trisomies of chromosomes 8, 13, 18, & 21 are seen in newborns, and no autosomal monosomies (only trisomy 21 has life expectancy >6 months) Multiple forms of sex-chromosome trisomies and one type of sex-chromosome monosomy occur 12 Aneuploidy in Humans cont. Trisomies and monosomies other than those found in newborn infants are known to occur Studies that monitor human pregnancies indicate that about half of all conceptions spontaneously abort during the first trimester About half of these pregnancies (~25% of all) had abnormalities in chromosome number or structure Aneuploidy in Humans cont. 2-13% of male sperm are aneuploid Increases with age, smoking, alcohol, caffeine, pollution,... Frequency of aneuploidy increases with female age 14 Changes in Euploidy Result in Various Kinds of Polyploidy Polyploidy is the presence of >2 sets of chromosomes in the nucleus of an organism Many types of polyploidy are possible E.g., triploid, tetraploid, pentaploid, hexaploid, etc. Changes in Euploidy Polyploidy can result from duplication of chromosome sets within a species (autopolyploidy) Via multiple fertilization or non-disjunction Changes in Euploidy Polyploidy can occur from combining chromosome sets of different species (allopolyploidy) Via hybridization (usually infertile) Polyploidy and Evolution Polyploidy results in a doubling of the entire genome Every gene is duplicated Polyploidy and Evolution Natural selection is relaxed on duplicated copies of genes so they are free to accumulate mutations Over time they often become inactive and degrade, but sometimes they may take on new functions Genes originating from genome duplication events retain many similarities in sequence and structure as well as their location relative to other syntenic genes Such genes are called paralogs and form gene families Hemoglobin Families Functions and Timing of Hemoglobin Family Chromosome Breakage Causes Loss, Gain, and Rearrangement of Chromosomes Mutations that result in loss or gain of chromosome segments can produce severe abnormalities due to gene dosage imbalances Changes may be large enough to detect microscopically (>100 kb) or small enough that only molecular methods can detect Large changes affect many genes, small changes affect few Partial Chromosome Deletion When a chromosome breaks, both DNA strands are severed at a chromosome break point The broken chromosome ends can adhere to other broken ends or the ends of intact chromosomes Or, because part of the broken chromosome is acentric (lacks a centromere), it may be lost during cell division No kinetochore for microtubule to attach to during mitosis Larger Chromosome Deletions Detachment of one chromosome arm leads to a terminal deletion; the broken fragment lacks a centromere and is lost during cell division Larger Chromosome Deletions An interstitial deletion is the loss of an internal portion of a chromosome, and results from two chromosome breaks Unequal Crossing Over Occasionally unequal crossover occurs between two homologous chromosomes during recombination in meiosis This can result in partial duplication on one chromosome and partial deletion on the other Uncommon, but occurs when repetitive regions of homologous chromosomes misalign Gene Duplications Gene dosage imbalance due to duplication may result in abnormal development Gene Duplications However, duplication & divergence is a major factor in evolution Genomes become larger & more complex Chromosome Breakage Leads to Inversion and Translocation of Chromosomes Sometimes chromosome breakage leads to reattachment of the wrong broken ends Reattachment in the wrong orientation leads to chromosome inversion Reattachment to a non-homologous chromosome leads to chromosome translocation If no critical genes are mutated and dose-sensitive genes remain in balance, there may be no phenotypic consequences Chromosome Inversion Two types of chromosome inversion can occur: In a paracentric inversion, the centromere is outside of the inverted region In a pericentric inversion, the centromere is within the inverted region 30 Chromosome Translocation Translocations occur when broken ends of non- homologous chromosomes are reattached Three types of translocations: Unbalanced translocations arise when a piece of one chromosome is translocated to a non-homolog and there is no reciprocal event Types of Translocations Reciprocal balanced translocations occur when pieces of two non- homologs switch places Robertsonian translocations, also called chromosome fusions, involve fusion of two non-homologous chromosomes 32 Robertsonian translocations (chromosomal fusions) Side-by-side comparison of homologous chromosomes of four closely related species Yunis & Prakash, 1982 Chromosome 2 of Sp. 1 p. 1 p. 2 p. 3 p. 4 S S S S Chromosome# 24 24 24 23 (haploid n) Sp. 4 Sp. 3 Sp. 2 Sp. 1 Decrease in 24 Chromosome# Ancestral state Sp. 1 Head-to-Head Telomere Fusion Site Chromosome 2 Fusion Site Fan et al., 2002  2.6 Mb Degenerate Centromeric Region Chromosome 2 Chromosome 2 Degenerate Centromere Hillier et al., 2005 Orangutan, Gorilla, & Human Chimpanzee Chromosome 2 Chromosomes 12 & 13 Chromosome# 24 24 24 23 (haploid n) tan zee n gu r illa an m a n a 4 OrSp. o Sp. 3 G mp 2 hiSp. Hu 1 Sp. C Decrease in Chromosome# Human chromosome 2 formed via fusion after the human- chimpanzee split, but before Homo spread throughout the world (MRCA) X