The origin of Mycobacterium tuberculosis infection has recently been dated to the Middle Paleolithic; around 70,000 years before the common era (BCE). At that time Homo sapiens was just another primate living in reduced groups in balance with nature, with discrete growth and a very low-density geographic occupation. Therefore, it is difficult to understand the origin of a highly virulent obligate human pathogen. We have designed a new SEIR model (TBSpectr) that considers tuberculosis (TB) clinical spectrum, by including a protection factor (p). The model fits current accepted growth rates for Middle Paleolithic (0.003%/year) and Neolithic (0,1%/year). The data obtained links the origin of M. tuberculosis ancient lineages in the Middle Paleolithic to the induction of mild TB forms (Sputum negative), thanks to a high p factor that was further enhanced by evolution towards modern lineages. The poor health status linked to the unequal society existing after the Neolithic revolution increased the incidence of more severe forms of TB (Sputum positive). This data supports the origin of TB as a well-tolerated highly persistent infection which could coevolve towards mutualism, shows the difficulty of eradicating it and highlights the imperative of providing better health conditions to humans to avoid its severity.