Chapter 6 Clusters and Repeats

6.1 Introduction A gene family consists of related genes that arose by duplication and variation from a single ancestral gene.

6.2 Gene Duplication Is a Major Force in Evolution Duplicated genes may diverge to generate different genes or one copy may become an inactive pseudogene. Figure 6.04: Duplicated genes may diverge or be silenced.

6.3 Globin Clusters Are Formed by Duplication and Divergence All globin genes are descended by duplication and mutation from an ancestral gene that had three exons. The ancestral gene gave rise to myoglobin, leghemoglobin, and α and  globins.

6.3 Globin Clusters Are Formed by Duplication and Divergence Figure 6.08: Globin genes have duplicated and diverged.

6.3 Globin Clusters Are Formed by Duplication and Divergence The α- and -globin genes separated in the period of early vertebrate evolution. After, duplications generated the individual clusters of separate α- and -like genes. Once a gene has been inactivated by mutation, it may accumulate further mutations and become a pseudogene. It is homologous to the active gene(s) but has no functional role.

6.3 Globin Clusters Are Formed by Duplication and Divergence Figure 6.05: Globin genes are organized in two clusters.

6.4 Sequence Divergence Is the Basis for the Molecular Clock The sequences of orthologous genes in different species vary at: replacement sites (where mutations have caused amino acid substitutions) silent sites (where mutation has not affected the amino acid sequence) Silent substitutions accumulate ~10× faster than replacement substitutions.

6.4 Sequence Divergence Is the Basis for the Molecular Clock The evolutionary divergence between two DNA sequences is measured by the corrected percent of positions at which the corresponding nucleotides differ. Mutations may accumulate at a more or less constant rate after genes separate The divergence between any pair of globin sequences is proportional to the time since they shared common ancestry.

6.4 Sequence Divergence Is the Basis for the Molecular Clock Figure 6.09: Silent substitutions occur more often than replacement substitutions.

6.5 The Rate of Neutral Substitution Can Be Measured from Divergence of Repeated Sequences The rate of substitution per year at neutral sites is greater in the mouse than in the human genome.

6.6 Unequal Crossing Over Rearranges Gene Clusters When a genome contains a cluster of genes with related sequences, mispairing between nonallelic loci can cause unequal crossing over. This produces a deletion in one recombinant chromosome and a corresponding duplication in the other.

6.6 Unequal Crossing Over Rearranges Gene Clusters Figure 6.12: Unequal crossing-over creates a duplication and a deletion.

6.6 Unequal Crossing Over Rearranges Gene Clusters Different thalassemias are caused by various deletions that eliminate α- or -globin genes. The severity of the disease depends on the individual deletion.

6.6 Unequal Crossing Over Rearranges Gene Clusters Figure 6.13: α-Thalassemias are caused by deletions. Figure 6.14: β-Thalassemias are caused by deletions.

6.7 Genes for rRNA Form Tandem Repeats Including an Invariant Transcription Unit Ribosomal RNA is coded by a large number of identical genes that are tandemly repeated to form one or more clusters. Each rDNA cluster is organized so that transcription units giving a joint precursor to the major rRNAs alternate with nontranscribed spacers.

The genes in an rDNA cluster all have an identical sequence. 6.7 Genes for rRNA Form Tandem Repeats Including an Invariant Transcription Unit The genes in an rDNA cluster all have an identical sequence. The nontranscribed spacers consist of shorter repeating units whose number varies so that the lengths of individual spacers are different.

Figure 6.18: The rDNA promoter has repetitious regions.

6.8 Crossover Fixation Could Maintain Identical Repeats Not all duplicated copies of genes are become pseudogenes. Unequal crossing over changes the size of a cluster of tandem repeats. Individual repeating units can be eliminated or can spread through the cluster.

6.9 Satellite DNAs Often Lie in Heterochromatin Highly repetitive DNA has a very short repeating sequence and no coding function. It occurs in large blocks that can have distinct physical properties. It is often the major constituent of centromeric heterochromatin.

Figure 6.20: Mouse satellite DNA forms a distinct band.

6.10 Arthropod Satellites Have Very Short Identical Repeats The repeating units of arthropod satellite DNAs are only a few nucleotides long. Most of the copies of the sequence are identical. Figure 6.22: D. virilis has four related satellites.

6.11 Mammalian Satellites Consist of Hierarchical Repeats Mouse satellite DNA has evolved by duplication and mutation of a short repeating unit. This gives a basic repeating unit of 234 bp in which the original half, quarter, and eighth repeats can be recognized.

6.11 Mammalian Satellites Consist of Hierarchical Repeats Figure 6.26: The mouse satellite DNA consensus is 9 bp.

6.12 Minisatellites Are Useful for Genetic Mapping The variation between microsatellites or minisatellites in individual genomes can be used to identify heredity unequivocally Done by showing that 50% of the bands in an individual are derived from a particular parent.

6.12 Minisatellites Are Useful for Genetic Mapping Figure 6.28: Minisatellite number differs between individual genomes.

Figure 6.29: Replication slippage changes repeat length.