In general, molecular clocks, appropriately chosen, have a finer time resolution than the fossil record, and they are a more reliable guide to the detailed structure of phylogenetic trees than are classical methods of tree construction, which are based on family resemblances in anatomy and embryonic development. For example, the precise family tree of great apes and humans was not settled until sufficient molecular sequence data accumulated in the 1980s to produce the pedigree shown previously in Figure 4–63. And with huge amounts of DNA sequence now determined from a wide variety of mammals, much better estimates of our relationship to them are being obtained (Figure 4–66).
A Comparison of Human and mouse Chromosomes Shows How the Structures of genomes Diverge
As would be expected, the human and chimpanzee genomes are much more alike than are the human and mouse genomes, even though all three genomes are roughly the same size and contain nearly identical sets of genes. Mouse and human lineages have had approximately 80 million years to diverge through accumulated mutations, versus 6 million years for humans and chimpanzees. In addition, as indicated in Figure 4–66, rodent lineages (represented by the rat and the mouse) have unusually fast molecular clocks, and have diverged from the human lineage more rapidly than otherwise expected.
While the way that the genome is organized into chromosomes is almost identical between humans and chimpanzees, this organization has diverged greatly between humans and mice. According to rough estimates, a total of about 180 breakage-and-rejoining events have occurred in the human and mouse lineages since these two species last shared a common ancestor. In the process, although the number of chromosomes is similar in the two species (23 per haploid genome in the human versus 20 in the mouse), their overall structures differ greatly. Nonetheless, even after the extensive genomic shuffling, there are many large blocks of DNA in which the gene order is the same in the human and the mouse. These stretches of conserved gene order in chromosomes are referred to as regions of synteny. Figure 4–67 illustrates how segments of the different mouse chromosomes map onto the human chromosome set. For much more distantly related vertebrates, such as chicken and human, the number of breakage-and-rejoining events has been much greater and the regions of synteny are much shorter; in addition, they are often hard to discern because of the divergence of the DNA sequences that they contain.
An unexpected conclusion from a detailed comparison of the complete mouse and human genome sequences, confirmed by subsequent comparisons between the genomes of other vertebrates, is that small blocks of DNA sequence are being deleted from and added to genomes at a surprisingly rapid rate. Thus, if we assume that our common ancestor had a genome of human size (about 3.2 billion nucleotide pairs), mice would have lost a total of about 45% of that genome from accumulated deletions during the past 80 million years, while humans would have lost about 25%. However, substantial sequence gains from many small chromosome duplications and from the multiplication of transposons have compensated for these deletions. As a result, our genome size is thought to be practically unchanged from that of the last common ancestor of humans and mice, while the mouse genome is smaller by only about 0.3 billion nucleotides.
Figure 4–66 A phylogenetic tree showing the evolutionary relationships of some present-day mammals. The length of each line is proportional to the number of “neutral substitutions”—that is, nucleotide changes at sites where there is assumed to be no purifying selection. (Adapted from g.m. Cooper et al., Genome Res. 15:901–913, 2005. with permission from Cold Spring Harbor laboratory Press.)
Good evidence for the loss of DNA sequences in small blocks during evolution can be obtained from a detailed comparison of regions of synteny in the human and mouse genomes. The comparative shrinkage of the mouse genome can be clearly seen from such comparisons, with the net loss of sequences scattered throughout the long stretches of DNA that are otherwise homologous (Figure 4–68).