26 August 2011

Ancient tryst fortified human immune systems

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Modern-day humans may have inherited a robust immune system from their interbreeding archaic ancestors.
Neanderthal DNA

Richard Green, a computational biologist at UCSC, holds replicas of the bones from which Neanderthal DNA was extracted. Credit: AFP/File, Jim Mackenzie

worldwide distribution in modern humans

The archaic HLA genes most likely provided resistance to pathogens that modern humans had not encountered in Africa. Because individuals who possessed the newly-acquired haplotypes then had an advantage over those who did not, they flourished as the new continents became populated. Shown is the worldwide distribution in modern humans for one of the two possible Neanderthal HLA-A-C haplotype sets – the haplotypes are common in Eurasia and not present in Africa. Credit: Science/AAAS

SYDNEY: Modern-day humans may have inherited a robust immune system from their interbreeding archaic ancestors.

New research indicates that some forms of the human leukocyte antigen (HLA) gene, identified as major contributors to the human immune system, originated from century-old relations with Neanderthals and another group of extinct humans, the Denisovans, to endure through thousands of years of evolution.

“Small numbers of mating [between] archaic individuals have made a major contribution to the immune systems of modern individuals,” said co-author Peter Parham, a professor of biology at Stanford University in California of the paper published today in Science.

“Around 50% of all modern HLA alleles are derived from archaic populations, and the other 50% are derived from early modern human populations.”

Re-defining the past

From the early 1990s, Parham and fellow researchers have been trying to gain a deeper understanding of the HLA genes through sequencing different forms, or alleles, of the genes from around the world. Surprisingly, one form, known as HLA-B73, held sections that were similar to ancestral sequences – those of the chimpanzee and gorilla. Parham hypothesised that these parts of the gene may have emerged from Neanderthals.

“The modern human population originated during the last migration out of Africa and into Eurasia,” said Parham. If the HLA allele had originated in Africa before the migration, frequencies of the allele would have been found there.

The researchers suggest that early modern humans migrated out of Africa and into Eurasia, where interbreeding with Denisovans in west Asia introduced the HLA immune defence genes into the human genome. Similar patterns are found in sequence analyses of Neanderthals and modern-day humans.

Really old contribution

Just last year, it was found that 4 to 6% of modern human material is derived from Denisovans. Similarly, approximately 4% of Neanderthal DNA can be found in the human genome today.

“The interesting thing is that this admixture is actually quite large – it is the equivalent of what your great-great-great grandparent gave you,” commented Paul Mason, a neuroanthropologist from Macquarie University in Sydney. “The contribution occurred before the advent of written language, which makes it really old.”

According to Parham, this means that there must have been something especially advantageous about these genes to persist through thousands of years of ‘survival of the fittest’. The HLA genes may have had some advantage to defend against infectious diseases of the environment in Eurasia thousands of years ago.

Where these gene forms prosper

Today, different forms of the HLA gene are existent in various capacities and various genomes around the world. The HLA-B*73 variant has a relatively low frequency of 5% within West Asian populations when compared to HLA-A*11, another form that has a 64% frequency rate in East Asia and Oceania.

It is estimated that 50% of HLA alleles in European populations today originated with admixture between early modern humans and archaic ancestors. And even more impressive, an estimated 80% of HLA alleles in Asians and 95% of HLA alleles in Papua New Guineans were derived from Denisovans and Neanderthals.

“This work could help guide disease-related research,” said Parham, and may provide a new, informative perspective on certain conundrums, such as the persistence of autoimmune diseases occurring most often in developed countries where a certain form of the HLA genes prosper.

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