Gene Duplication and Evolution Jan Aagaard [email protected] • Readings – Required: Aguileta et al., 2004. JME 59:177. – Optional: Gonzalez et al., 2005. Science 307:1434. • Genome Sciences seminar on gene duplication – Wednesday 3/9, 3:30 in Hitchcock 132 J. B. S. Haldane H. J. Muller • Final exam question on gene duplication material! 1892-1962 1890-1967 The Causes of Evolution. 1932 1935. Genetics 17:237 Overview Three Classes of Gene Duplication 1. Individual Gene Duplication • Mechanisms and frequency of gene Duplication of an individual gene duplication 2. Segmental Gene Duplications • Fate of duplicate genes Duplication of portions of chromosomes • Evolution duplicate genes 3. Chromosomal or Whole Genome Duplications Duplication of entire individial chromosomes (aneuploidy) or – example of β-globin genes the entire set of chromosomes (polyploidy) 1. Individual Gene Duplications 2. Segmental Gene Duplication Most commonly result of unequal crossing over Result of transposition of segments of a chromosome between two chromosomes (sister chromatids or (1 to >200 kb) within the chromosome or to other homologous chromosomes) chromosomes Human Chromosomes A. B. X X Intra-chromosomal Inter-chromasomal Bailey et al., 2002. AJHG 70:83. 1 3. Changes in Ploidy Identifying Duplicate Genes Result of incomplete partitioning of chromosomes Sequence, gene structure, physical proximity during cell division -- may be partial (aneuploidy) or involve the entire chromosome complement (polyploidy) Phylogenetic Analyses a Orthologs Meiosis I Meiosis II Species Tree Gene Tree b A a ? c B b Paralogs C c d a’ b’ Orthologs D d c’ Modified from Griffiths et al., 2000. An Introduction to Genetic Analysis. Fig. 18-16 d’ Gene Duplication is Frequent...... loss of Duplicates Frequent, too! Summary to Here....... Oryza sativa Arabidopsis thaliana ~30,000 genes ~22,000 genes 23% paralogs 24% paralogs • Gene duplication is common via several Modified from mechanisms Blanc and Wolfe, 2004. Plant Cell 16:1667. • Majority of duplicates rapidly lost Percent of Paralogs Silent Substitutions 1. ~ 1% of organism’s genes duplicated per 1 My • What about retained duplicates? 2. 1/2-life of paralogs ~ 2-7 My -may be much longer for polyploid paralogs (~ 23 My)? Two Possible Fates for Paralogs....... several different mechanisms Globin Gene Family >800 Mya Modified from Force et al, 1999. Human Chromosomes 450-500 Mya Genetics 151:1531. 16 α-globins Embryo Fetus Adult ε Gγ Aγ ψη δ β Adult/Embryo 11 150-200 Mya β-globins 100-140 22 ~55 ~80 Myoglobin 2a. Retention of 2b. Retention of Myoglobin ε Gγ Aγ δ β 1. Loss of Paralog Paralog: novel Paralog: Embryo/Fetus function complementarity α-globins Adult Embryo 2c. Retention of Paralog: dosage 2 Aguileta et al., 2004. Embryo JME 59:177. 1. Neufunctionalization Adaptive evolution following gene duplication (dN/dS or ω Embryo/Fetus > 1)? 2. Subfunctionalization Purifying selection Adult following gene duplication (dN/dS or ω < 1)? Embryo Embryo/Fetus Adult Embryo/ Adult Fetus Embryo ε Gγ Aγ ψη δ β Embryo Embryo/Fetus Adult Adult ε Gγ Aγ ψη δ β 3.