When the human genome is examined, the chromosomes appear to have undergone only minimal rearrangement in the 100 million years since the last common ancestor of eutherian mammals. However, when individual humans are examined or when the human genome is compared with that of chimpanzees, a large number of small indels and SNPs can be detected. How are these observations reconciled?

You have isolated a gene that is important for the production of milk and wish to study its regulation. You examine the genomes of human, mouse, dog, chicken, pufferfish, and yeast and note that all genomes except yeast have an orthologous gene.

What does the existence of orthologous genes in chicken and pufferfish tell you about the function of this gene?

A modification of the two-hybrid system, called the one-hybrid system, is used for identifying proteins that can bind specific DNA sequences. In this method, the DNA sequence to be tested, the bait, is fused to a TATA box to drive expression of a reporter gene. The reporter gene is often chosen to complement a mutant phenotype; for example, a HIS gene may be used in a his⁻ mutant yeast strain. A cDNA library is constructed with the cDNA sequences translationally fused to the GAL4 activation domain and transformed into this yeast strain. Diagram how trans-acting proteins that bind to cis-acting regulatory sequences can be identified using a one-hybrid screen.

You have isolated a gene that is important for the production of milk and wish to study its regulation. You examine the genomes of human, mouse, dog, chicken, pufferfish, and yeast and note that all genomes except yeast have an orthologous gene.

How would you identify the regulatory elements important for the expression of your isolated gene in mammary glands?

Symbiodinium minutum is a dinoflagellate with a genome size that encodes more than 40,000 protein-coding genes. In contrast, the genome of Plasmodium falciparum has only a little more than 5000 protein-coding genes. Both Symbiodinium and Plasmodium are members of the Alveolate lineage of eukaryotes. What might be the cause of such a wide variation in their genome sizes?

Substantial fractions of the genomes of many plants consist of segmental duplications; for example, approximately 40% of genes in the Arabidopsis genome are duplicated. How might you approach the functional characterization of such genes using reverse genetics?

Consider the phylogenetic trees below pertaining to three related species (A, B, and C) that share a common ancestor (last common ancestor, or LCA). The lineage leading to species A diverges before the divergence of species B and C.

For gene Z, gene duplications have occurred in all species. Define orthology and paralogy relationships for the different Z genes.