Projects

HLA and Genomic Diversity in Southern India

“In drawing lessons from community genetics one has to remember that the gene pool differing in terms of time, space, origin and spread will differ in their immune repertoire as well and these diverse gene pools may not be equally susceptible to an epidemic or infectious disease. Further different genes may also be involved in different populations and even genome scans may not identify all such genes in all populations. Thus a systematic study on HLA genes, non HLA genes, STR/SNP loci, microsatellite markers, MHC haplotypes and other various polymorphic loci of MHC and other regions, NRY, mitDNA etc, might provide valuable clue on population structure, random drift, bottle-neck effect (after severe selection events), selection, migration, diversity etc, limited to our imagination, interpretation and collective effort of all of us.”

The proposal aims at obtaining evidence to the extent to identify the cause and effects of this genomic diversity, employing high throughput DNA and genomic tools, as a part of 14th ihwc exercise.

II: INVITATION:

It is not possible that any one laboratory cope up with all those proposed above in the limited time available to each one of us: It is a collective effort and hence interested ihwc participating laboratories are invited to join this component and study any genes / genomes, of their interest and expertise, including various regions of MHC. Please indicate how much minimum of samples you would require.

For your participation & suggestions please contact:

Dr. RM. Pitchappan
Senior Professor & Head
Department of Immunology
Centre for Advanced Studies in Functional Genomics - School of Biological Sciences
Centre for Excellence in Genomic Sciences - Madurai Kamaraj University
MADURAI, Tamil Nadu, 625 021, INDIA

Email: pitchappanrm@yahoo.co.uk
Fax: +(91 452) 2459181 or 2459139
Tel: + (91 452) 2458269 (off); 2569889 ®

III. The Plan of Work:

Fifteen different ‘populations’ (breeding isolates = castes) (table 1) from the state of Tamil Nadu and nearby Kerala, the southern most part of India will be studied. The available ethnographic notes indicate many of them to be very ancient and isolated populations. An at random blood sample of 200 individuals from each population will be collected, DNA extracted, quality controlled and stored at –70C. All relevant background population information will be obtained in a precoded questionaire, for analysis.

These samples will be made available to those interested in studying any genetic / genomic polymorphisms in these populations. The same set of coded samples of two populations will first be provided to all the participating laboratory and the results will be submitted to the 14th ihwc central data processing and analysis laboratory: the sample id will be decoded at the time of analysis and interpreted. Based on this preliminary exercise on two populations, the rest of the populations will be studied in the workshop.

The Intellectual propriety rights and disclosures, will be guided by the regulations of the Indian government, International fora and science ethics. The participating laboratories of the ihwc may not patent, publish & interpret the results or transfer the samples to any other third party, without the written consent of the organizing laboratory i.e., Prof. Pitchappan, Madurai Kamaraj University, India. All the results will be made available in the public domain by all the participating laboratory in the ihwc database.

IV. BACKGROUND INFORMATION:

‘Journey of Man’: “All of us are literally Africans underneath the skin, Brothers and Sisters separated by mere 2000 generations” , thus concluded Spencer Wells, the scientist from Oxford, narrating the ‘Journey of Man’ in his National Geographic Channel International exclusive telecasted on 15th December and 18th December 2002 in India and thereafter all over the world till 21st January in PBS channel in U.S.A. As Luca Cavalli Sforza, father of human population genetics from Stanford says ‘Genetics is the biological history’ and it has traced the migration of man around the world. (Book from Penguin Press and VHS tape from Tigress production available commercially).

Prof. RM. Pitchappan, Senior Professor & Head, Department of Immunology, School of Biological Sciences played a crucial role in this discovery, identifying the first coastal migration of modern man (Homo sapiens) from Africa to Australia, through India, 50,000 years ago. Thus India was the second continent, Homo sapiens colonized and expanded.

Palaeoclimatological evidences suggest that fifty thousand years ago, moisture was tied up in expanding polar sheets of northern hemisphere, temperature was lower by 10 degree Celcius, African forests dried up, the sea was 100 meters lower than they are today exposing 200 km of land off the west coast of India! Sri Lanka and India were connected by a land bridge: similarly the Malayan archipelago until Indonesia was connected with the main land just leaving 250 km of ocean bridges with Australia. The mankind was at the verge of extinction in Africa. This makes sense that this coastal high way made it easier for a small band of people to leave Africa, through the north eastern horn and undertake the long journey. A small group of people, speaking ‘click’ language and related to San Bushmen of Namibia, probably started this coastal journey and reached Australia in another 1000 years.

Non recombinant Y (NRY) chromosome is a stable region of our genome and it is a time machine: the genetic and migration history of a man is imprinted in this part of the genome and one can identify the migration route, lineages and determine the time of origin using maximum parsimony and other similar methods. The study identified two major waves of migration out of Africa: first a coastal migration 50,000 years ago and the second migration to Central Asia, 45,000 years ago. The second migration expanded in Central Asia lead dispersal towards Europe, Americas, south Asia and China. M130 NRY was the marker for the first coastal migration and M89 for the second leading to M9 that expanded in Central Asia and gave rise to M 45, the marker of people who colonized Europe, M175 the Chinese lineage and M20 an Indian lineage (Wells et al 2001).

Pitchappan studied three ‘breeding isolates’ (castes) of Tamil Nadu in southern India, viz. Piramalai Kallars, Yadhavas and Sourashtrans and had big surprises. All these people living now in Madurai possessed 5-7% M130 marker. This marker is present in 10% of Malaysian, 15% of New Guineans and 60% of Australian Aborigines! This confirmed the first coastal migration from Africa to Australia, through India: an evidence that could not be obtained by archaeology has been obtained by genetics. Archaeological excavations in Fan Hien cave and Batadomba Lena cave in Sri Lanka contained anatomically modern humans and artefacts providing earliest sign of Upper Paleolithic in south Asia, dating 31,000 years.

The second surprise was Piramalai Kallars possessed the highest frequency of M20, 50%, a 30,000 years old marker found in low frequencies in Middle East and common in Pakistan. Yadhavas possessed a higher frequency of M172, a 10,000 years old derivative of M89. Sourashtrans of Madurai possessed another 10,000-year-old M17 in higher frequencies: it is an offshoot of M45 enroot to the European M173. These HLA DRB1* polymorphism was also striking (Shanmugalakshmi et al 2003).

Yet another surprise was that majority of the females in southern India belonged to earlier migrations and has had expanded in this region for long. Thus 60% of the population of southern India possessed M mitochondrial DNA lineages. The Central Asian expansion was also identified clearly marked by U2i marker (Kivisild et al., 2003). Thus the ancient migrant males seems to have been replaced by subsequent migrant males, amalgamating the females into their fold: The female dominance in the sedentary Dravidian culture and female worship might refletct this picture. Thus India is replete of various populations migrated time immemorial, living and evolving in sympatric isolation. This isolation and diversity reflect in many HLA studies of Pitchappan & his group (Pitchappan 2002) and it might have relevance in disease susceptibility, vaccinology and pharmaco-genomics.

The Piramalai Kallars and Yadhavas studied by Pitchappan may represent earlier Dravidian populations (30,000-10,000 yrs old isolates): Cambridge scholars have suggested that Dravidian language was spoken first in Fertile Crescent and spread to Middle East and the whole of India some 10,000 years ago. Dravidian culture might have been quite popular earlier days though. In the opinion of Prof. Pitchappan ‘Dravidian’ were more a culture, and then a ‘linguistic family’ and the last a ‘sub-divided gene pool’: ‘caste system was the grandest genetic experiment ever done on Homo sapients’ thus exclaimed Dobzhansky. This raises many interesting questions on the origin and antecedence of Dravidian culture itself: it might prove to be the most ancient cultures of the world. This hypothesis opens up a new vista of science and further inquiry into the rich cultural and genetic heritage of southern India. This is a fertile area of research for linguists, anthropologists, archaeologists, and geneticists: a multipronged, concerted effort with genomics tools will pay rich dividends. We can learn more from these populations for the betterment of the world at large, Pitchappan believes.

Projects

HLA and Genomic Diversity in Southern India

Premise

Invitation

Work Plan

Background

Questionaire

Update No. 1 (November 2004)

Update No. 2 (April 2005)

I. PREMISE:

II: INVITATION:

III. The Plan of Work:

IV. BACKGROUND INFORMATION:

Further readings: