Tag Archives: genomics

Genomics for future anthropologists & archeologists

An awesome use of genomics and proteomics in archeology and paleopathogenomics (yes I just invented the word!)

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Origin of species: through gene regulation?

“How does evolution occur?” This has been a central question in biology. Does evolution occur because a new mutation results in a new protein or because the same gene is regulated differently? How do new morphological structures evolve? How does speciation occur? A recent paper in Science ties principles in evolutionary biology, development biology, and molecular biology to answer these exact questions.

Distalless protein (dll), which is highly conserved across many genera, seems to have EVOLVED A NOVEL FUNCTION in a particular species of insect (Rheumatobates rileyi) to generate male specific antennal appendages. Males possessing these appendages have increased chances of reproducing therefore, have higher fitness (see video below). There could be two reasons for the development of these antennal appendages: first, dll in this particular species is shorter than all other species and second, dll is differentially regulated in this species. Although dll in R. rileyi appears to be shortened,  I feel that its differential expression may be more important in creating this morphology. dll is an important protein in development and therefore, it is pleiotrophic (see figure on the right below). Thus, it is likely that any alteration of the original function by the shortened protein would result in death. One scenario could be that a cis-mediated regulatory change in dll expression causes it to be expressed at a novel developmental stage in a novel tissue where some other male-specific proteins are also expressed. Interactions between dll and such male-specific protein(s) results in the formation of antennal appandages.

So, what does this study tell us about how evolution occurs? Well, one way evolution by natural selection occurs is not through new mutations that alters the function of existing proteins but through mutations that result in modifications in regulation of existing proteins to acquire novel function. Existing proteins may acquire novel functions if they are ectopically expressed, i.e, in developmental stages or tissues where they are normally not expressed. Most of the times ectopic expression may either provide no benefit to the individuals or even be detrimental but sometimes, ectopic expression may allow these proteins to interact with other proteins expressed in that tissue at that developmental stage to perform new functions. This new function may confer some reproductive advantage to that individual, therefore enhancing what population geneticists/evolutionary biologists call ‘fitness’. Over time, these individuals will take over in the population. If this population remains isolated from the ancestral population for a long period of time, it may give rise to a novel species (not this study but can be imagined).

This is a cool example of how integrating many areas of biology (evolutionary, developmental, molecular, and entomology) can elucidate novel genetic mechanisms underlying phenotypic diversity.

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Phylo: Crowdsourcing BIOINFORMATICS and GENOMICS

For many reasons multiple species DNA alignment is a hard problem. One reason it is hard is because as evolutionary relationship between organisms increase, the similarities in their DNA sequence decrease. Many times we encounter gaps and duplications that make accurate alignment very difficult.

Computer algorithms are getting better (compare CLUSTAL-W to  Clustal Omega), it is still pretty darn difficult to accurately align multiple species. A lot of time and effort is needed to manually inspect alignments performed even by the best multiple species aligner. A handful of scientists can only take it so far…so, crowdsourcing helps here.

One can use an algorithm to perform multiple species alignments of multiple genomes. These alignments can then be made publicly available to public such that they can, in their leisure, improve them by manually intervention. Recently, I came across PHYLO which is a GAME, yes a  GAME!!!! in which multiple species alignments of human genome that are potentially linked to various genetic disorders, such as breast cancer can be manually curated by the public. “Every alignment is received, analyzed, and stored in a database, where it will eventually be re-introduced back into the global alignment as an optimization.”

This is a wonderful opportunity for the public to learn a little about bioinformatics and to understand about evolution. So folks, substitute your AngryBirds with Phylo and help yourself increase your chances of living longer by helping the scientific community move closer towards finding ‘cures’ for these diseases.

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Mapping Human Brain:An awesome video at TED


This was an awesome presentation demonstrating appication of genomics to understand human biology. This would be wonderful to educate general public and high school students about the following:

  1. Biological systems are very complex: thousands of genes produce thousands of proteins at various times that mediate billions of neuronal interactions. Genomics tools (microarray: the things with green dots in this talk)
  2.  A lot of work and time is needed to learn fundamentals of biology: many scientists are needed to gather biological specimen, perform experiments, and to analyze data. In this video only 2 brains were used. Imagine using hundreds of tissues.
  3. Integration of computer programming in visualization: today, because of genomics massive amount of data can be generated in little time. However, in order to analyze and understand the data, computational tools are needed. Once the data is analyzed, computer graphics is needed to visualize the data (the brain with nice colors in this talk). Therefore, computational biologists and artists are becoming important components of the genomics community.
  4. Applications of such studies: Once we accumulate many such studies, they can be used to design drugs or to prevent a disease in general population. This takes even more time and resources.

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Could Rautes, Kusundas, Chepangs, Rajis or Tharus be the first peoples to colonize the Himalayas 7000 years ago?

Rautes: The last nomads of Nepal

This picture belongs to Kishore K. Sharma, an awesome Nepali photographer. Please do visit his blog by clicking on this picture to view more pictures of the Rautes.

History of Nepal, as taught in academic institutions, starts with Gopalavamshis, the so-called first rulers of Nepal, followed by Mahispalavamshis, Kiratis, Licchavis, Mallas, and Shahs in that order. However it only represents the political history of Nepal at its best. To understand history of Nepal in its completeness, one must learn about the history of the peoples of Nepal.

Human inhabitation of the Himalayan foothills, known as present day Nepal, predates the dawn of civilization and the Gopalavamshis because prehistoric stone tools of “Patu industry,” a non-agricultural Mesothilic culture unique to Nepal were recovered in Central Nepal[1]. Two distinct types of tools, the Patu tools resembling the 10-12 thousand years old Hoabinhian culture and another resembling 10-30 thousand years old culture in India highlight three important points about ancient Nepali history: first, modern day Nepal has been inhabited by humans since the Pleistocene; second, Nepal has been cosmopolitan even in the Mesolithic harboring Indian and South East Asian cultures, and finally, the Patu people had an unique cultural identity by the Mesolithic.

But what happened to the Patu people? It is curious that a few nomadic hunter-gatherer tribes live/until recently lived the Mesolithic lifestyle in central Nepal, where the “Patu industry” once existed. Could they be the descendants of the Mesothilic humans that developed the first Himalayan culture?

Kusundas (aka Myahak, Ban Rajas) and Chepangs (aka Prajas) are one of the highly marginalized tribes in Nepal. Until a few decades ago both these tribes were nomadic hunter-gatherers. With forests gone, Kusundas were forced to desert their nomadic life and enter villages, which caused annihilation of their culture, traditions, and languages. Only a few Kusundas today, speak their native language. Like the Kusundas, Chepangs were also nomadic hunters and gatherers in central Nepal. Destruction of forests has forced Chepangs to adopt a semi-nomadic life in the non-yielding slopes of the Mahabharat range.

In addition to their hunter-gatherer lifestyles, linguistic and anthropological evidence suggest that Kusundas and Chepangs have been living in central Nepal since ancient times. Both the Kusundas and the Chepangs were officially first reported by B.H. Hodgson, a British naturalist and ethnologist in mid-nineteenth century, as “broken tribes” living nearly “in a state of nature” and carrying bows and arrows with no relationship with the rest of the “civilized races” of the country[2]. Later CJF Forbes found more plausible relationship between Chepangs and Khyens (Kiiyen) and Kumis of Arakan hills in Burma (Myanmar) and even concluded that Chepangs may have entered Nepal from the east [3]. Unlike Chepang, Kusunda language is difficult to classify as it similarities with various unrelated language groups such as Austro-Asiatic (Munda)[4], Tibeto-Burman, and even Indo-Pacific[5]. It is now widely recognized as a language isolate[6]: a language distinct from all other languages spoken in Nepal.

Although both Chepang and Kusunda languages seem to be unrelated to any other languages in Nepal, they appear to be linguistically closely related to each other (see Figure1). It is plausible that Chepangs and Kusundas have cohabited the Mahabharata hills and centuries of linguistic exchange may have resulted in their language similarities. Furthermore, anthropological evidence seems to corroborate the linguistic antiquity between these tribes, for example, both the Kusundas and the Chepangs have a folk legend according to which the Kusundas are the descendants of Kusa (thus the name Kusunda) and Chepangs are the descendants of Lava, both the sons of Rama and Sita of the Ramayana. Furthermore, interviews with Chepang traditional healers and medicine men revealed hundreds of plants used for diverse purposes and many of them were previously not documented.[7] The tremendous ethno-botanical knowledge of the Chepangs further substantiates their occupation of central Himalayas since ancient times for such knowledge of local flora can only be built with time. Hence, Kusundas and Chepangs, by virtue of their nomadic life styles and lack of linguistic affinities with any other languages of Nepal, may have inhabited the Himalayan foothills long before other ethnicities emigrated.

Recently, genomics has been used to infer the demographic histories of human populations throughout the world. Analysis of Kusunda genome in a recent issue of Science[8] supports some of the linguistic evidence and indicates that Kusundas are related to Tibeto-Burman speaking North East-Asian populations such as Hezhens, Oroqens and Mongolians but are not related to the Australian or Papuan Aborigines and virtually unrelated to any of the human populations from East or South Asia. Remarkably, a Kusunda specific genetic component is evident; however, without further analysis it is difficult to determine whether this component is due to long period of population isolation or due to ancient age of the population.

Genetic and linguistic evidence argues that Kusundas are possibly the most ancient of Nepali populations. They , may have come into contact with Mundas and Burmese in Eastern Himalayan foothills in ancient times. Words burrowed from these languages may have remained in Kusunda language to date. However, more work is needed to determine whether the Kusunda specific genetic components are a result of recent inbreeding due to population isolation or whether they are archaic genome components due to Kusundas’ antiquity in the Himalayan foothills.

Although it is tempting to crown Kusundas as the eldest peoples of Nepal, other nomadic/semi-nomadic tribes of central Nepal cannot be ignored. Genetic analysis of Chepangs may show that they have also cohabited the Mahabharata hills for centuries. It is also noteworthy that many other tribes along with Kusundas and Chepangs may have inhabited central Nepal since ancient times. For example, the Tharus may be descendants of inhabitants of the Terai since the Paleolithic. Tremendous ethnic and cultural diversity within Tharus that spread throughout the Terai region attest their occupation of the land for centuries. However, it is interesting that there is little linguistic similarity between the Tharus and the hunter-gatherers of central Nepal suggesting that there may have been very little interactions between the populations of the hills and that of the plains. Furthermore, Rautes that are still nomadic and Rajis that recently gave up nomadic lifestyle may have resided in central Nepal before the advent of agriculture. Many more ethnicities of Nepal may have inhabited the Himalayan foothills since ancient times but little is known about them. Hence, it is really important to investigate the history of all the peoples of Nepal for accurate presentation of Nepali history and their origins as such studies are also interesting from the perspectives of human evolution. Himalayas are believed to have acted as a barrier for gene flow between the Indian subcontinent and Central Asia. However, the fertile Himalayan foothills with diverse flora and fauna may have been a Mesolithic melting pot for migrants from both the sides of the Himalayas since Mesolithic times. Understanding the origins and demographic histories of present tribes of Nepal may reveal novel aspects of ancient human dynamics in Asia.

In summary, there is abundant evidence that present day Nepal was inhabited by humans since the Paleolithic and a culture unique to Nepal existed by Mesolithic. It is possible that hunter-gatherer populations currently residing in central Nepal, such as Kusundas, Chepangs, Rautes, and Rajis may be the descendents of the Patu people that developed the first culture of Nepal some 7000 years ago. There is a dire need for additional archeological, anthropological, linguistic, and genomic studies to understand the ancient history of Nepal accurately.


[2] Hodgson, B. H. (1848) J. Asiat. Soc. Bengal 17 , 73–78

[3] Forbes, C. J. F. (1877) Journal of the Royal Asiatic Society of Great Britain and Ireland, New Series, Vol. 9,No. 2,  pp. 421-424

[4] Reinhard, J. & Toba, T. (1970) A Preliminary Linguistic Analysis and Vocabulary of the Kusunda Language (Summer Institute of Linguistics, Kirtipur, Nepal).

[5] Whitehouse et al. (2004) Kusunda: An Indo-Pacific language in Nepal. PNAS Vol. 101,No. 15, pp. 5692-5695

[6] Watters, D. (2005) Notes on Kusunda grammar (a language isolate of Nepal). Kathmandu: National Foundation for the Development of Indigenous Nationalities.

[7] Rijal A. 2011. Surviving on knowledge: ethnobotany of Chepang community from midhills of Nepal. Ethnobotany Res Appl 9:181-215.

[8] Rasmussen, M. et al. (2011) An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia. Science Vol. 334, No. 6052, pp.94-98

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Filed under Anthropology, Evolution, Human Evolution, My Life My Thoughts, Nepal