Genomes and Their Evolution

Lysozyme and α-Lactalbumin Comparison

Lysozyme and α-lactalbumin have similar protein structures, as shown in computer-generated ribbon models.
Amino acid sequences of the two proteins are compared, with amino acids arranged in groups of ten for ease of reading, using single-letter amino acid codes.
Identical amino acids are highlighted, and dashes indicate gaps introduced to optimize alignment.
Even non-identical amino acids may behave similarly if they are structurally and chemically alike (e.g., similarly acidic or basic).

Gene Evolution

Protein structure changes can augment function by increasing stability, enhancing ligand binding, or altering other properties.
Many protein-coding genes have multiple copies of related exons, possibly arising from duplication and divergence.
Collagen, an extracellular matrix protein, has a repetitive amino acid sequence reflecting the repetitive pattern of exons in the collagen gene.

Exon Shuffling

Exon shuffling involves mixing and matching different exons within a gene or between nonallelic genes due to errors in meiotic recombination.
This can lead to new proteins with novel combinations of functions.
Tissue plasminogen activator (TPA) is an example of a protein believed to have arisen by exon shuffling.
TPA has four domains encoded by exons, with one exon present in two copies.
Each type of exon in TPA is also found in other proteins.
Meiotic errors could have moved exons from ancestral genes (epidermal growth factor, fibronectin, and plasminogen) into the evolving TPA gene.
Subsequent duplication of the "kringle" exon (K) from the plasminogen gene after its movement into the TPA gene accounts for the two copies of this exon in the TPA gene today.

Transposable Elements and Genome Evolution

Transposable elements play an important role in shaping a genome over evolutionary time.
They can promote recombination, disrupt genes or control elements, and carry genes or exons to new locations.
Transposable elements scattered throughout the genome facilitate recombination between nonhomologous chromosomes by providing homologous regions for crossing over.
Most such recombination events are detrimental, causing chromosomal translocations and other changes that may be lethal.
Occasionally, a recombination event may be advantageous.

Consequences of Transposable Element Movement

A transposable element jumping into a protein-coding sequence prevents the production of a normal transcript of the gene.
Introns provide a “safety zone” as transposable elements will be spliced out.
Insertion within a regulatory sequence may lead to increased or decreased production of proteins.
Transposition caused both types of effects on pigment-synthesizing enzymes in McClintock's corn kernels.
Some Alu transposable elements in the human genome regulate the expression of human genes.

Transposable Elements Carrying Genes

During transposition, a transposable element may carry a gene or a group of genes to a new position in the genome.
This may account for the location of the α-globin and B-globin gene families on different human chromosomes.
An exon from one gene may be inserted into another gene via transposition into the intron of a protein-coding gene.
If the inserted exon is retained in the RNA transcript during RNA splicing, the synthesized protein will have an additional domain, potentially conferring a new function.
Small heritable changes are usually harmful or have no effect but can, in rare cases, be beneficial. The resulting genetic diversity provides raw material for natural selection.

Comparing Genome Sequences

Comparing genome sequences from different species reveals information about evolutionary history.
Comparative studies of genetic programs directing embryonic development clarify mechanisms generating life-form diversity.

Genomes and Evolutionary Relationships

The more similar in sequence the genes and genomes of two species are, the more closely related those species are in their evolutionary history.
Comparing genomes of closely related species sheds light on more recent evolutionary events. Distantly related species enhances our picture of the evolution of organisms and biological processes.
Evolutionary relationships between species can be represented by a tree, with each branch point marking the divergence of two lineages.

Comparative Genomics

Determining which genes have remained similar (highly conserved) in distantly related species can clarify evolutionary relationships.
Comparisons of gene sequences of bacteria, archaea, and eukaryotes indicate that these three groups diverged 2-4 billion years ago.
Comparative genomic studies confirm the relevance of research on model organisms to our understanding of biology.
A 2015 study showed that 47% of important yeast genes could be replaced by the human gene, underscoring the common origin of yeasts and humans.

Comparing Closely Related Species

The genomes of two closely related species are likely to be organized similarly.
Only a small number of gene differences are found when their genomes are compared.
These genetic differences can be correlated with phenotypic differences between the two species.
Researchers compare the human genome with the genomes of chimpanzees, mice, rats, and other mammals.
Identifying genes shared by all of these species but not by nonmammals gives clues about what it takes to make a mammal.
Finding the genes shared by chimpanzees and humans but not by rodents tells us something about primates.
Comparing the human genome with that of the chimpanzee helps us understand what genomic information defines a human or a chimpanzee.

Human and Chimpanzee Genome Comparison

The human and chimpanzee genomes, thought to have diverged about 6 million years ago, differ by only 1.2% in single nucleotide substitutions.
There is a further 2.7% difference due to insertions or deletions of larger regions, with many insertions being duplications or repetitive DNA.
A third of the human duplications are not present in the chimpanzee genome.
There are more Alu elements in the human genome than in the chimpanzee genome, and the latter contains many copies of a retroviral provirus not present in humans.
Sequencing of the bonobo genome revealed that in some regions, human sequences were more closely related to either chimpanzee or bonobo sequences than chimpanzee or bonobo sequences were to each other.

Genetic Basis of Species Differences

Biologists are studying specific genes and types of genes that differ between chimpanzees and humans and comparing them with their counterparts in other mammals to discover the basis for the phenotypic differences between chimpanzees and humans.
Genes involved in defense against malaria and tuberculosis as well as at least one gene that regulates brain size.
The genes that seem to be evolving the fastest are those that code for transcription factors.

FOXP2 Gene

One transcription factor whose gene shows evidence of rapid change in the human lineage is called $FOXP2$ .
Mutations in this gene can produce severe speech and language impairment in humans.
The $FOXP2$ gene is expressed in the brains of zebra finches and canaries during song learning.
The homozygous mutant mice had malformed brains and failed to emit normal ultrasonic vocalizations, and mice with one faulty copy of the gene also showed significant problems with vocalization.

Neanderthals and FOXP2

Neanderthals ( $Homo neanderthalensis$ ) are members of the same genus to which humans ( $Homo sapiens$ ) belong.
Some groups of humans and Neanderthals co-existed and interbred for a period of time before Neanderthals went extinct about 30,000 years ago.
Their $FOXP2$ gene sequence encodes a protein identical to that of humans, suggesting that Neanderthals may have been capable of speech.

Genetic Variation in Humans

The amount of DNA variation among humans is small compared to that of many other species.
Much of our diversity seems to be in the form of single nucleotide polymorphisms (SNPs).
SNPs are single base-pair sites where genetic variation is found in at least 1% of the population.
In the human genome, SNPs occur on average about once in 100-300 base pairs.
Scientists have already identified the locations of several million SNP sites in the human genome and continue to find additional SNPs.

Copy-Number Variants (CNVs)

The most surprising discovery has been the widespread occurrence of copy-number variants (CNVs), loci where some individuals have one or multiple copies of a particular gene or genetic region rather than the standard two copies.
CNVs result from regions of the genome being duplicated or deleted inconsistently within the population.
One study of 40 people found more than 8,000 CNVs involving 13% of the genes in the genome.
CNVs are more likely to have phenotypic consequences and to play a role in complex diseases and disorders.