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EARLY TBEARLY TUBERCULOSIS. DNA evidence of human tuberculosis from these 9,000-year-old bones of a woman and an infant suggests the disease appeared in humans much earlier than thought. Full story. credit: I. Hershkovitz

TB or not TB? That was the question created by a pair of human skeletons excavated more than a decade ago at a 9,000-year-old village submerged off Israel’s coast.

Bone damage apparently produced by some type of infection created the Shakespearean dilemma that puzzled excavation director and anthropologist Israel Hershkovitz, head of the Dan David Laboratory for the Search and Study of Modern Humans at Tel Aviv University in Israel.

Thanks to a genetic analysis of the skeletons directed by Helen Donoghue and Mark Spigelman, both of University College London, Hershkovitz now knows that his team unearthed the earliest known cases of human tuberculosis. A roughly 25-year–old mother had apparently passed on the bacterial infection to her 1-year–old child, after which they both died and were buried together.

Other instances of human tuberculosis that have been confirmed by ancient DNA analyses date to no more than about 5,500 years ago in Egypt and Sweden.

Examination of DNA from the Israeli skeletons supports the idea, based on earlier studies of genetic variation in different strains of modern tuberculosis bacteria, that bovine tuberculosis evolved after human tuberculosis did, Hershkovitz and his colleagues conclude in a report published online October 15 in PLoS ONE.

Work at the ancient village of Atlit-Yam, which has been covered by water for the past several thousand years, yielded the skeletons and some of the earliest evidence for agriculture and for cattle domestication.

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CITY SUBMERGEDA semi-circular construction made of stones, some more than two meters tall, stood at the center of the now submerged city Atlit-Yam and probably hosted ritual ceremonies. credit: I. Hershkovitz

Infection-related bone damage is difficult to pin on any specific disease, notes biological anthropologist George Armelagos of Emory University in Atlanta. “The genetic analysis of the Atlit-Yam skeletons really opens up our understanding of the human form of tuberculosis by showing that it was not derived from cattle but evolved well before animal domestication,” Armelagos says.

According to one longstanding hypothesis, tuberculosis initially infected people who drank the milk of domesticated cattle that carried a unique strain of the bacterium.

New DNA data from the two Atlit-Yam skeletons “give us the best evidence yet that in a community with domesticated animals but before dairying, the infecting strain of tuberculosis was actually the human pathogen,” Donoghue says.

Unpublished DNA analyses of two additional human skeletons found at Atlit-Yam have also yielded genetic evidence of human tuberculosis, according to Hershkovitz.

He estimates that human tuberculosis first evolved around 10,000 years ago, when agriculture’s emergence led to densely populated settlements that acted as petri dishes for infection. Tuberculosis may have infected small numbers of people before that, but the bacteria could not have spread widely in small bands of nomadic hunter-gatherers, the Israeli anthropologist argues.

Hershkovitz suspects that tuberculosis epidemics led to the demise of early farming communities and their distinctive cultural practices around 8,000 years ago. A new wave of agricultural settlements, which featured the first examples of pottery making, soon followed.

In Armelagos’ view, human tuberculosis could have originated as early as 20,000 years ago. Confirmation of the bacterium’s evolutionary age will depend on finding late Stone Age skeletons that show signs of infection, and then successfully extracting DNA from them.

Earlier this year, another research team reported that a 500,000-year–old Homo erectus skull found in Turkey displayed bone damage that probably resulted from tuberculosis. Both Hershkovitz and Armelagos regard that claim as unsubstantiated. “It is now clear that any identification of tuberculosis in a skeletal population without the confirmation of DNA analysis is pure speculation,” Hershkovitz says.

Donoghue and her coworkers were able to extract pieces of DNA from infection-damaged spots on the two Israeli skeletons. Salt water, sand and clay had covered the bodies, providing excellent conditions for bone preservation. Atlit-Yam was located within a coastal marshland before its immersion by the rising ocean.

Five different genetic sequences obtained from the skeletons matched corresponding sequences of DNA from Mycobacterium tuberculosis, the principal agent of human tuberculosis.

In addition, the Atlit-Yam bones yielded fatty acids found in the cell walls of M. tuberculosis.

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