Essential Cell Biology 5th edition

326 CHAPTER 9 How Genes and Genomes Evolve
The instructions needed to produce a multicellular animal from a fertilized
egg are provided, in large part, by the regulatory DNA sequences
associated with each gene. These noncoding DNA sequences contain,
scattered within them, dozens of separate regulatory elements, including
short DNA segments that serve as binding sites for specific transcription
regulators (discussed in Chapter 8). Regulatory DNA sequences ultimately
dictate each organism’s developmental program—the rules its
cells follow as they proliferate, assess their positions in the embryo, and
specialize by switching on and off specific genes at the right time and
place. The evolution of species is likely to have more to do with innovations
in regulatory DNA sequences than in the proteins or functional
RNAs the genes encode.
Given the importance of regulatory DNA sequences in defining the characteristics
of a species, one place to begin searching for clues to identity is
in the regulatory DNA sequences that are highly conserved across mammalian
species, but are altered or absent in our own genome. One study
identified more than 500 such sequences, providing some intriguing clues
as to what makes us human. One of these regulatory DNA sequences,
missing in humans, seems to suppress the proliferation of neurons in the
brain. Although further investigation is required, it is possible that the
loss of this sequence—or changes in other neural-specific regulatory DNA
sequences—played an instrumental role in the evolution of the human
brain.
Another regulatory DNA sequence lost in the human lineage directs the
formation of penile spines—structures present in a wide variety of mammals
including chimpanzees, bonobos, gorillas, orangutans, gibbons,
rhesus monkeys, and bushbabies. Whether the loss of these structures
provides some advantage to humans is not known; it could be that the
change is neutral—neither advantageous nor harmful. Regardless, it is a
characteristic that makes us unique.
Thanks to such genetic comparisons, we are beginning to unravel the
secrets of how our genome evolved to produce the qualities that define us
as a species. But these analyses can only provide information about our
distant evolutionary past. To learn about the more recent events in the
history of modern Homo sapiens, we are turning to the genomes of our
closest extinct relations, as we see next.
The Genome of Extinct Neanderthals Reveals Much
about What Makes Us Human
In 2010, investigators completed their analysis of the first Neanderthal
genome. One of our closest evolutionary relatives, Neanderthals lived
side-by-side with the ancestors of modern humans in Europe and Western
Asia. By comparing the Neanderthal genome sequence—obtained from
DNA that was extracted from a fossilized bone fragment found in a
cave in Croatia—with those of people from different parts of the world,
researchers identified a handful of genomic regions that have undergone
a sudden spurt of changes in modern humans. These regions include
genes involved in metabolism, brain development, the voice box, and
the shape of the skeleton, particularly the rib cage and brow—all features
thought to differ between modern humans and our extinct cousins.
Remarkably, these studies also revealed that many modern humans—
particularly those that hail from Europe and Asia—share about 2% of
their genomes with Neanderthals. This genetic overlap indicates that our
ancestors mated with Neanderthals—before outcompeting or actively
exterminating them—on the way out of Africa (Figure 9−37). This ancient
relationship left a permanent mark in the human genome.