oa Lactase Persistence Variants as Markers to Study Human Demographic Movements in the Light of Animal Domestication and Milk Culture

Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (-13910 C>T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). Recent studies have demonstrated that lactase persistence (LP) variants -13910*T and -13915*G have emerged from different allelic backgrounds and occur at very high frequencies in different populations. Iranian and Arabian populations have been reported to differ significantly in genetic patterns at these LP variants. The Arabian population is characterized by a 50-60 percent frequency of a -13915*G allele, attributable to its consumption of camel milk. This allele has not been detected so far among the Iranian population which, on the contrary, is similar to the European and Near Eastern populations showing a moderate frequency of -13910*T allele, which occurs at a significantly lower frequency in Arabia. In this background, we intended to determine the putative genetic source for the Indian Muslim population as mtDNA and Y chromosomal markers showed relatively low levels of genetic differentiation between their two potential sources of origin, Iran and Arabia. We sequenced for a 400 bp fragment around -13910 region of the LCT gene in 747 individuals from different regions of India. The variant -13910*T was widely observed in both Indian Muslim (Indian Shia-10 percent Indian Sunni-10 percent Dawoodi Bohra (TN)-14 percent, Dawoodi Bohra (GUJ)-11 percent, Mappla-2 percent, Iranian Shia-4 percent), and non-Muslim populations (North India-19 percent, West India-23 percent, South India-10 percent). The Iranian population also exhibited the same mutation with 10 percent frequency. The Arabian-specific -13915*G variant was completely absent from the Indian population, yet at the same position a new -13915*C variant (Mappla-1percent and South India-1 percent), likely to be an Indian-specific mutation was observed. The wide spread of the LP variant -13910*T among the Indian Muslim populations examined excludes the possibility of major genetic input from Arabia and corroborates the gene flow primarily from Iran, rather than directly from the Arabian Peninsula. Thus, the LCT gene correlating with LP in humans reveals the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture and cattle domestication.

Muthukrishnan Eaaswarkhanth, Irene Gallego Romero, Toomas Kivisild, Kumarasamy Thangaraj