Rhesus Macaque

The Rhesus Macaque (Macaca mulatta), often called the Rhesus Monkey, is one of the best known species of Old World monkeys.

Adult males measure approximately 53 centimeters on average and weigh an average of 7.7 kilograms. Females are smaller, averaging 47 centimeters in length and 5.3 kilograms in weight. The Rhesus macaque is brown or grey in color and has a pink face which is typically bereft of fur. Its tail is of medium length, averaging between 20.7 and 22.9 centimeters long. It typically has a lifespan of about 25 years.

The species is common throughout Afghanistan, northern India, and southern China. There is also a colony that is well established and thriving in Florida, USA. This population gained a foothold niche in the Silver River State Park as a result of being released by a tour boat operator known locally as "Colonel Tooey" to enhance his "Jungle Cruise" ride some time around the Spring of 1938. A traditional story that the monkeys were released for scenery enhancement in the Tarzan movies that were filmed at that location is false, as the only Tarzan movie filmed in the area, 1939's Tarzan Finds a Son, contains no Rhesus Macaques.

In science
The Rhesus Macaque is well known to science owing to its relatively easy upkeep in captivity, and has been used extensively in medical and biological research. It has given its name to the Rhesus factor, one of the elements of a person's blood group, by the discoverers of the factor, Karl Landsteiner and Alexander S. Wiener. The Rhesus Macaque was also used in the well-known experiments on maternal deprivation carried out in the 1950s by comparative psychologist Harry Harlow. NASA launched Rhesus Macaques into space during the 1950s and 60s, and the Soviet/Russian space program launched them into space as recently as 1997 as part of the Bion missions.

In January of 2000, the Rhesus Macaque became the first cloned primate with the birth of Tetra. January 2001 saw the birth of ANDi, the first transgenic primate; ANDi carries foreign genes originally from a jellyfish.

Work on the genome of the Rhesus Macaque was completed in 2007, making Rhesus Macaque the second non-human primate to have its genome sequenced. The study shows that humans and macaques share about 93% of their DNA sequence and shared a common ancestor roughly 25 million years ago.

Though most studies of the Rhesus Macaque are from various locations in northern India, some of our knowledge of the natural behaviour of the species comes from studies carried out on a colony established by the Caribbean Primate Research Center of the University of Puerto Rico on the island of Cayo Santiago, off Puerto Rico. There are no predators on the island, and humans are not permitted to land except as part of the research programmes. The colony is provisioned to some extent, but about 50% of its food comes from natural foraging. In other more controlled settings, these macaques often enjoy Fig Newtons and apricots, and are particularly keen on "pouching" large quantities of marshmallows!

In nature
Inhabiting arid, open areas, the Rhesus Macaque may be found in grasslands, woodlands, and in mountainous regions up to 2,500 metres in elevation. It is a good swimmer and is said to enjoy the activity. The Rhesus Macaque is noted for its tendency to move from rural to urban areas, coming to rely on handouts or refuse from humans. It has become a pest in some areas, perceived as a possible risk to public health and safety.

A diurnal animal, the Rhesus Macaque is both arboreal and terrestrial; it is mostly herbivorous and feeds on leaves and pine needles, roots, and the occasional insect or small animal. The monkey has specialized pouch-like cheeks, allowing it to temporarily hoard its food. The gathered morsels are eaten sometime later, in safe surroundings.

According to Melnick, Hoelzer, Absher, and Ashley, "The rhesus monkey has the widest geographic range of any nonhuman primate," occupying a great diversity of altitudes throughout Central, South, and Southeast Asia.

There is a notable colony of Rhesus Monkeys on Morgan Island in lowcountry South Carolina. They were imported in the 1970s for use in the local labs and are by all accounts thriving.

Behaviour and reproduction
Like any other macaques, the Rhesus troop comprises a mixture of males and females. The troop may contain up to 180 individuals, but 20 is the average. Females may outnumber the males by a ratio of 4:1. The social hierarchy is also matriarchal, rank dependent on lineage to the lead female. Care of young and territory surveillance duties are shared amongst the troop. While females are more or less placid, males are typically rowdy between themselves. The Rhesus Macaque is characterised as a vociferous monkey. Monkeys that discover food will normally advertise the fact by specific calls, though it has been claimed that young or subordinate monkeys will sometimes seek to avoid doing so if their discovery has gone unobserved. Females cycle similar to humans with menstrual cycles of around 28 days.

Mating is not confined to a specific season. Gestation may last from 135-194 days. Females are mature by three years of age, and males at four. The typical lifespan of a rhesus monkey in captivity is approximately 15-20 years for males and 20-25 years for females. These monkeys rarely live beyond 15 years of age in the wild.

Classification
There are several subspecies of Rhesus Macaque:
 * Macaca mulatta mulatta
 * Macaca mulatta villosa
 * Macaca mulatta vestita
 * Macaca mulatta lasiota
 * Macaca mulatta sanctijohannis
 * Macaca mulatta brevicauda

Sequencing the genome
Comparison of rhesus (macaque mulatta) chimpanzees and humans revealed the structure of ancestral primate genomes, positive selection pressure and lineage-specific expansions and contractions of gene families.

"The goal is to reconstruct the history of every gene in the human genome," said Evan Eichler, University of Washington, Seattle. DNA from different branches of the primate tree will allow us "to trace back the evolutionary changes that occurred at various time points, leading from the common ancestors of the primate clade to Homo sapiens," said Bruce Lahn, University of Chicago.

After the human and chimpanzee genomes were sequenced and compared, it was usually impossible to tell whether differences were the result of the human or chimpanzee gene changing from the common ancestor. After the Rhesus macaque genome was sequenced, 3 genes could be compared. If 2 genes were the same, they are presumed to be the original gene.

The chimpanzee and human genome, which diverged 6 million years ago, had 98% identity and many conserved regulatory regions. Comparing the macaque and human genome, which diverged 25 million years ago and had 93% identity, further identified evolutionary pressure and gene function.

Like the chimpanzee, changes were on the level of gene rearrangements rather than single mutations. There were frequent insertions, deletions, changes in the order and number of genes, and segmental duplications near gaps, centromeres and telomeres. So macaque, chimpanzee and human chromosomes are mosaics of each other.

Surprisingly, some normal gene sequences in healthy macaques and chimpanzees cause profound disease in humans. For example, the normal sequence of phenylalanine hydroxylase in macaques and chimpanzees is the mutated sequence responsible for phenylketonuria in humans. So humans must have been under evolutionary pressure to adopt a different mechanism.

Some gene families are conserved or under evolutionary pressure and expansion in all 3 primate species, while some are under expansion uniquely in human, chimpanzee or macaque.

For example, cholesterol pathways are conserved in all 3 species (and other primate species). In all 3 species, immune response genes are under positive selection, and genes of T cell-mediated immunity, signal transduction, cell adhesion, and membrane proteins generally. Genes for keratin, which produce hair shafts, were rapidly evolving in all 3 species, possibly because of climate change or mate selection. The X chromosome has 3 times more rearrangements than other chromosomes. The macaque gained 1,358 genes by duplication.

Triangulation of human, chimpanzee and macaque sequences showed expansion of gene families in each species.

The PKFP gene, important in sugar (fructose) metabolism, is expanded in macaques, possibly because of their high-fruit diet. So are genes for the olfactory receptor, cytochrome P450 (which degrades toxins), and CCL3L1-CCL4 (associated in humans with HIV susceptibility).

Immune genes are expanded in macaques, relative to all 4 great ape species. The macaque genome has 33 major histocompatibility genes, 3 times that of human. This has clinical significance because the macaque is used as an experimental model of the human immune system.

In humans, the PRAME (preferentially expressed antigen of melanoma) gene family is expanded. It is actively expressed in cancers but normally testis-specific, possibly involved in spermatogenesis. The PRAME family has 26 members on human chromosome 1. In the macaque, it has 8, and has been very simple and stable for millions of years. The PRAME family arose in translocations in the common mouse-primate ancestor 85 million years ago, and is expanded on mouse chromosome 4.

Agilent and Affymetrix have macaque DNA microarrays with 20,000 gene sequences, and they are used in macaque research. For example, Michael Katze of University of Washington, Seattle, infected macaques with 1918 and modern influenza. The DNA microarray showed the macaque genomic response to human influenza on a cellular level in each tissue. Both viruses stimulated innate immune system inflammation, but the 1918 flu stimulated stronger and more persistent inflammation, causing extensive tissue damage, and it did not stimulate the interferon-1 pathway. The DNA response showed a transition from innate to adaptive immune response over 7 days.