Duplication and Jan Aagaard [email protected]

• Readings – Required: Aguileta et al., 2004. JME 59:177. – Optional: Gonzalez et al., 2005. Science 307:1434. • 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. 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 Duplication of portions of • Evolution duplicate genes 3. Chromosomal or Whole Genome Duplications Duplication of entire individial chromosomes () or – example of β-globin genes the entire set of chromosomes ()

1. Individual Gene Duplications 2. Segmental Gene Duplication

Most commonly result of Result of transposition of segments of a 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 division -- may be partial (aneuploidy) or involve the entire chromosome complement (polyploidy) Phylogenetic Analyses

a Orthologs Meiosis I Meiosis II 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. Cell 16:1667. • Majority of duplicates rapidly lost Percent of Paralogs

Silent Substitutions 1. ~ 1% of ’s genes duplicated per 1 My • What about retained duplicates? 2. 1/2- of paralogs ~ 2-7 My -may be much longer for polyploid paralogs (~ 23 My)?

Two Possible Fates for Paralogs...... several different mechanisms Globin

>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