The Omics Revolution

The new technologies that embrace the term -omics have evolved to address increasingly complex biological questions arising out of the postgenomics era. I describe some of these advanced techniques toward the end of this book. Briefly they encompass techniques like DNA microarray technology, real-time polymerase chain reaction, denaturing hplc, two-dimensional (2-D) protein electrophoresis coupled with matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry, and in silico bioin-formatics. These state-of-the-art techniques permit us to venture into the world of pro-teomics, transcriptomics, metabolomics, nutrigenomics, methylomics, and perhaps at the ultimate level to understand the "interactome." The interactome is defined as the sum of all protein interactions in the cell. A graphical representation of a typical "interaction map" looks like a massive aggregated collection of hairy dandelion seeds and is hugely complex (Figure 1.9). Such interactomes are often simplified into "functional interaction maps" in which proteins are allocated to functional categories (i.e., protein degradation, carbohydrate metabolism, and signal transduction). This provides a simpler three-dimensional (3-D) rendering of the network of cellular functions.

At the leading edge of scientific endeavor, it is becoming increasingly difficult to pigeonhole one's research interest. This book is a prime example of how interests in food, nutrition, genetics, molecular biology, clinical medicine, evolutionary theory, and anthropology come together to address the most fundamental of all human questions: "What does being human mean, and how did the condition arise?" Essentially, what is the meaning of life?

As an educator within our university system, I became frustrated by the notion that human nutrition is simply all about food, its constituents, and how they prevent disease or contribute, to it. As this book proves, nutrition is a far more diverse and philosophically deep subject than many students (and educators) think, and one that has never been more relevant than it is today. The two novel subdisciplines within nutrition that are now increasingly important are nutrigenomics and nutritional genetics. Peter Gillies (9) has defined these terms as follows: "Nutrigenomics refers to the prospective analysis of differences among nutrients with regard to the regulation of gene expression. In this context, nutrigenomics is a discovery science driven by the paradigms of molecular biology, enabled by microarray technology, and integrated on an informatics platform" (10,11). Gillies goes on to define nutrigenet-ics, or what many people refer to as nutritional genetics, as "the retrospective analysis of genetic variations among individuals with regard to their clinical response to specific nutrients. In this context, nutrigenetics is an applied science driven by the paradigms of

The Rise of Modem Man:

"Out of Africa Replacement" or a "Multiregional" Evolution?

The Concepts:

The "Eve" hypothesis to support an "out of Africa" model for human evolution has much to commend it; this "out of Africa replacement" scenario is based on the molecular relatedness between African groups from within the continent, and between groups from Africa and other regions. The "out of Africa replacement model" assumes a human population originated in Africa 150,000 years ago with Eve as its source, and then radiated out, supplanting other human groups en route. However, this is only one possible option to account for our origins. An alternative model proposes that modern man evolved slowly from ancestral humans in many different areas of the world. This is the "multiregional model". This paradigm is based on populations gradually evolving into modern humans in many different locations. Implicit in this model is that differences in physiognomy (skin and hair color, build, etc.) between geographically distinct human populations have a longer adaptive chronology than would be implied by an "out of Africa" model. A third paradigm exists—"the assimilation model" contends that our origins were in fact African, but regional groups of archaic humans like the Neanderthals made a substantive contribution to our existing gene pool.

The Evidence:

The debate between replacement (perhaps more logically referred to as uniregional) and multiregional models remains to be resolved: In a 2002 review, Satta and Takahata si weigh up the evidence for both models and conclude that the uniregional model is the most likely option to have occurred. Similarly, a recent 2005 paper by Ray and colleagues S2 describes the use of multilocus genetic data to infer the geographic origin of humans and distinguish between uni- and multiregional models. Using 377 genetic markers, they claim that East Africa is the most likely place of origin for modern humans and the source of human expansion into the Old World. However, Eswaran and colleagues S3 prefer a model in which the modern human phenotype originated in Africa and then advanced globally by local demic diffusion, hybridization, and natural selection. This phenotypic sweep represents an intermediate between the uniregional model (sweep of new species) and the multiregional model (independent single-locus selective sweeps). Overall, the emphasis of research findings, however, does seem to be toward a uniregional approach. Caramelli and coworkers S4 have typed ancient DNA sequences from Cro-Magnon man and found variability similar to contemporary humans, but at variance to the chronologically similar Neanderthals, indicating genetic discontinuity that makes it difficult to reconcile that both Neanderthals and early humans contributed to the current European gene pool. Some problems in evaluating the evidence are highlighted in a paper by Collard and Franchino S5. They suggest that the difficulties of pair-wise difference analysis of morphological/fossil data cannot be used to generate reliable estimates of primate phylogeny. Rather, molecular phylogeny is a more robust marker. Clearly, a consensus view on our origins is not easy to arrive at. It has been suggested that an exclusive focus on mtDNA has led to a one-sided and hence misleading picture of modern human origins that emphasizes a migration out of Africa with replacement ss. It is, however, difficult to ignore that, given limited variation within nonrecombined sequences of the autosomes, there is insufficient power to distinguish between models of human origin. Where autosomal loci do exhibit the required resolution, they point to the uniregional model S7. One thing is sure, though, this important debate on our origins is likely to continue into the foreseeable future.

Specific references to this subject:

51. Satta V, STakahata N. Out of Africa with regional interbreeding? Modern human origins. Bioessays 2002: 24: 871-5.

52. Ray N, Currat M, Berlhier P, & Exooffier L. Recovering the geographic origin of early modern humans by realistic and spatially explicit simulations. Genome Res 2005: 15: 1161-7.

53. Eswaran V. & Harpending H. Rogers AR. Genomics refutes an exclusively African origin of humans. J Hum Evol 2005: 49: 1-18.

54. Caramelli D, Lalueza-Fox C, Vernesi C, et al. Evidence for a genetic discontinuity between Neandertals and 24,000-year-old anatomically modern Europeans. Proc Natl Acad Sci U S A 2003:100: 6593-7. Epub 2003 May 12

55. Collard M, & Franchino N. Pairwise difference analysis in modern human origins research. J Hum Evol 2002: 43:323-52.

56. Harpending H. & Eswaran V. Tracing modern human origins. Science 2006: 309,1995.

57. Macauley V, Hill C, Achilli A. et al. Tracing modern human origins. Science 2006: 309,1995.

Figure 1.6. Contemporary theories to explain the recent ascent of humankind are based on two models: an "out of Africa replacement model" in which we evolved as a species in Africa, and radiated out to colonize the planet, and a model in which "multiregional evolution" of our species occurred.

Out of Africa pattern of human migration—The African replacement hypothesis

Modem humans entered'aflH" slowly populated Asia around 40,000 years ago t_ r y p

Gene markers show that modern humans left Africa around 70,000 years ago supplanting earlier humans such as Neanderthal man

The slow push through Asia eventually traversed what is today's Bering Sea, but what was then a land bridge, and modern humans first appeared in the New World around 15-20,000 years ago

Modern humans appeared 200,000 years ago in East Africa and dispersed throughout the Old World where they eventually replaced all archaic human species

Modern humans arrived in Australasia 50,000 years ago after a slow skirting of the Indian Ocean

The greatest genetic diversity exists within Africa, and tells us that this continent was the original cradle of modern humans, and it is from here that our species expanded to populate Earth

Figure 1.7. This figure shows the pattern of migratory radiation that our species took when leaving Africa based on the "out of Africa replacement model," which is the favored paradigm for our recent evolutionary past.

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