Several trends are evident when we compare the genomes of prokaryotes to those of eukaryotes. There is a general trend from smaller to larger genomes, but with fewer genes in a given length of DNA. Humans have 500 to 1,500 times as many base pairs in their genome as most prokaryotes, but only 5 to 15 times as many genes. Most of the DNA in a prokaryote genome codes for protein, tRNA, or rRNA. The small amount of noncoding DNA consists mainly of regulatory sequences. In eukaryotes, most of the DNA (98.5% in humans) does not code for protein or RNA. Gene-related regulatory sequences and introns account for 24% of the human genome. Introns account for most of the difference in average length of eukaryotic (27,000 base pairs) and prokaryotic genes (1,000 base pairs). Most intergenic DNA is repetitive DNA, present in multiple copies in the genome. Transposable elements and related sequences make up 44% of the entire human genome. The first evidence for transposable elements came from geneticist Barbara McClintock’s breeding experiments with Indian corn (maize) in the 1940s and 1950s. Eukaryotic transposable elements are of two types: transposons, which move within a genome by means of a DNA intermediate, and retrotransposons, which move by means of an RNA intermediate, a transcript of the retrotransposon DNA. Transposons can move by a “cut and paste” mechanism, which removes the element from its original site, or by a “copy and paste” mechanism, which leaves a copy behind. Retrotransposons always leave a copy at the original site, since they are initially transcribed into an RNA intermediate. Most transposons are retrotransposons, in which the transcribed RNA includes the code for an enzyme that catalyzes the insertion of the retrotransposon and may include a gene for reverse transcriptase. Reverse transcriptase uses the RNA molecule originally transcribed from the retrotransposon as a template to synthesize a double-stranded DNA copy. Multiple copies of transposable elements and related sequences are scattered throughout eukaryotic genomes. A single unit is hundreds or thousands of base pairs long, and the dispersed “copies” are similar but not identical to one another. Some of the copies are transposable elements and some are related sequences that have lost the ability to move. Transposable elements and related sequences make up 25–50% of most mammalian genomes, and an even higher percentage in amphibians and angiosperms. In primates, a large portion of transposable element–related DNA consists of a family of similar sequences called Alu elements. These sequences account for approximately 10% of the human genome. Alu elements are about 300 nucleotides long, shorter than most functional transposable elements, and they do not code for protein. Many Alu elements are transcribed into RNA molecules. However, their cellular function is unknown. Repetitive DNA that is not related to transposable elements probably arose by mistakes that occurred during DNA replication or recombination. Repetitive DNA accounts for about 15% of the human genome. Five percent of the human genome consists of large-segment duplications in which 10,000 to 300,000 nucleotide pairs seem to have been copied from one chromosomal location to another. Simple sequence DNA contains many copies of tandemly repeated short sequences of 15–500 nucleotides. There may be as many as several hundred thousand repetitions of a nucleotide sequence. Simple sequence DNA makes up 3% of the human genome. Much of the genome’s simple sequence DNA is located at chromosomal telomeres and centromeres, suggesting that it plays a structural role. The DNA at centromeres is essential for the separation of chromatids in cell division and may also help to organize the chromatin within the interphase nucleus. Telomeric DNA prevents gene loss as DNA shortens with each round of replication and also binds proteins that protect the ends of a chromosome from degradation or attachment to other chromosomes. Gene families have evolved by duplication of ancestral genes. Sequences coding for proteins and structural RNAs compose a mere 1.5% of the human genome. If introns and regulatory sequences are included, gene-related DNA makes up 25% of the human genome. In humans, solitary genes present in one copy per haploid set of chromosomes make up only half of the total coding DNA. The rest occurs in multigene families, collections of identical or very similar genes. Some multigene families consist of identical DNA sequences that may be clustered tandemly. These code for RNA products or for histone proteins. For example, the three largest rRNA molecules are encoded in a single transcription unit that is repeated tandemly hundreds to thousands of times. This transcript is cleaved to yield three rRNA molecules that combine with proteins and one other kind of rRNA to form ribosomal subunits. Two related families of nonidentical genes encode globins, a group of proteins that include the α (alpha) and β (beta) polypeptide sequences of hemoglobin. The different versions of each globin subunit are expressed at different times in development, allowing hemoglobin to function effectively in the changing environment of the developing animal. Within both the ? and ? families are sequences that are expressed during the embryonic, fetal, and/or adult stage of development. In humans, the embryonic and fetal hemoglobins have higher affinity for oxygen than do adult forms, ensuring transfer of oxygen from mother to developing fetus. Also found in the globin gene family clusters are several pseudogenes, DNA sequences similar to real genes that do not yield functional proteins. Concept 19.5 Duplications, rearrangements, and mutations of DNA contribute to genome evolution The earliest forms of life likely had a minimal number of genes, including only those necessary for survival and reproduction. The size of genomes has increased over evolutionary time, with the extra genetic material providing raw material for gene diversification. An accident in meiosis can result in one or more extra sets of chromosomes, a condition known as polyploidy. In a polyploid organism, one complete set of genes can provide essential functions for the organism. The genes in the extra set may diverge by accumulating mutations. These variations may persist if the organism carrying them survives and reproduces. In this way, genes with novel functions may evolve. Errors during meiosis due to unequal crossing over during Prophase I can lead to duplication of individual genes. Slippage during DNA replication can result in deletion or duplication of DNA regions. Such errors can lead to regions of repeats, such as simple sequence DNA. Major rearrangements of at least one set of genes occur during immune system differentiation. Duplication events can lead to the evolution of genes with related functions, such as the a-globin and b-globin gene families. A comparison of gene sequences within a multigene family indicates that they all evolved from one common ancestral globin gene, which was duplicated and diverged about 450–500 million years ago. After the duplication events, the differences between the genes in the d family arose from mutations that accumulated in the gene copies over many generations. The necessary function provided by an ?-globin protein was fulfilled by one gene, while other copies of the ?-globin gene accumulated random mutations. Some mutations may have altered the function of the protein product in ways that were beneficial to the organism without changing its oxygen-carrying function. The similarity in the amino acid sequences of the various ?-globin and ?-globin proteins supports this model of gene duplication and mutation. Random mutations accumulating over time in the pseudogenes have destroyed their function. In other gene families, one copy of a duplicated gene can undergo alterations that lead to a completely new function for the protein product. The genes for lysozyme and ?-lactalbumin are good examples. Lysozyme is an enzyme that helps prevent infection by hydrolyzing bacterial cell walls. ??????-lactalbumin is a nonenzymatic protein that plays a role in mammalian milk production. Both genes are found in mammals, while only lysozyme is found in birds. The two proteins are similar in their amino acids sequences and 3-D structures. These findings suggest that at some time after the bird and mammalian lineage had separated, the lysozyme gene underwent a duplication event in the mammalian lineage but not in the avian lineage. Subsequently, one copy of the duplicated lysozyme gene evolved into a gene encoding ?-lactalbumin, a protein with a completely different function.