A related approach in the search for the important mutations that contributed to human evolution likewise begins with DNA sequences that have been conserved during mammalian evolution, but rather than screening for accelerated changes in individual nucleotides, it focuses instead on chromosome sites that have experienced deletions in the 6 million years since our lineage diverged from that of chimpanzees. More than 500 such sequences—conserved among other species but deleted in humans—have been discovered. Each deletion removes an average of 95 nucleotides of DNA sequence. Only one of these deletions affects a protein-coding region: the rest are thought to alter regions that affect how nearby genes are expressed, an expectation that has been experimentally confirmed in a few cases. A large proportion of the presumed regulatory regions identified in this way lie near genes that affect neural function and/or near genes involved in steroid signaling, suggesting that changes in the nervous system and in immune or reproductive functions have played an especially important role in human evolution.
mutations in the DNA Sequences That Control gene Expression Have Driven many of the Evolutionary Changes in vertebrates
The vast hoard of genomic sequence data now being accumulated can be explored in many other ways to reveal events that happened even hundreds of millions of years ago. For example, one can attempt to trace the origins of the regulatory elements in DNA that have played critical parts in vertebrate evolution. One such study began with the identification of nearly 3 million noncoding sequences, averaging 28 base pairs in length, that have been conserved in recent vertebrate evolution while being absent in more ancient ancestors. Each of these special non-coding sequences is likely to represent a functional innovation peculiar to a particular branch of the vertebrate family tree, and most of them are thought to consist of regulatory DNA that governs the expression of a neighboring gene. Given full genome sequences, one can identify the genes that lie closest and thus appear most likely to have fallen under the sway of these novel regulatory elements. By comparing many different species, with known divergence times, one can also estimate when each such regulatory element came into existence as a conserved feature. The findings suggest remarkable evolutionary differences between the various functional classes of genes (Figure 4–74). Conserved regulatory elements that originated early in vertebrate evolution—that is, more than about 300 million years ago, which is when the mammalian lineage split from the lineage leading to birds and reptiles—seem to be mostly associated with genes that code for transcription regulator proteins and for proteins with roles in organizing embryonic development. Then came an era when the regulatory DNA innovations arose next to genes coding for receptors for extracellular signals. Finally, over the course of the past 100 million years, the regulatory innovations seem to have been concentrated in the neighborhood of genes coding for proteins (such as protein kinases) that function to modify other proteins post-translationally.
Many questions remain to be answered about these phenomena and what they mean. One possible interpretation is that the logic—the circuit diagram—of the gene regulatory network in vertebrates was established early, and that more recent evolutionary change has mainly occurred through the tuning of quantitative parameters. This could help to explain why, among the mammals, for example, the basic body plan—the topology of the tissues and organs—has been largely conserved.
gene Duplication Also Provides an Important Source of genetic Novelty During Evolution
Evolution depends on the creation of new genes, as well as on the modification of those that already exist. How does this occur? When we compare organisms that seem very different—a primate with a rodent, for example, or a mouse with a fish—we rarely encounter genes in the one species that have no homolog in the reception of extracellular signals HUMAN 500 400 300 200 100 0 millions of years before present