Can fat explain the human brain's big bang evolution?—Horrobin's leads for comparative and functional genomics

Abstract

When David Horrobin suggested that phospholipid and fatty acid metabolism played a major role in human evolution, his ‘fat utilization hypothesis’ unified intriguing work from paleoanthropology, evolutionary biology, genetic and nervous system research in a novel and coherent lipid-related context. Interestingly, unlike most other evolutionary concepts, the hypothesis allows specific predictions which can be empirically tested in the near future. This paper summarizes some of Horrobin's intriguing propositions and suggests as to how approaches of comparative genomics published in Cell, Nature, Science and elsewhere since 1997 may be used to examine his evolutionary hypothesis. Indeed, systematic investigations of the genomic clock in the species’ mitochondrial DNA, the Y and autosomal chomosomes as evidence of evolutionary relationships and distinctions can help to scrutinize associated predictions for their validity, namely that key mutations which differentiate us from Neanderthals and from great apes are in the genes coding for proteins which regulate fat metabolism, and particularly the phospholipid metabolism of the synapses of the brain. It is concluded that beyond clues to humans’ relationships with living primates and to the Neanderthals’ cognitive performance and their disappearance, the suggested molecular clock analyses may provide crucial insights into the biochemical evolution—and means of possible manipulation—of our brain.

Introduction

In 2003, Wildman et al. published a comparison of 97 human genes to chimpanzees’ and other primates’ counterparts [1] and discussed their observation that humans and chimpanzees share close to 99 per cent of their genetic material with a focus on the degree of evolutionary relationships between us and our closest evolutionary relatives. Similarly, evolutionary relationships between humans and Neanderthals were discussed in Cell [2] and elsewhere [3], [4] when Krings et al. published their recovery of Neanderthal DNA [5].

Without doubt, genomics may contribute to answering a whole series of related questions—old and new: (i) Does a genetic conformity of 99 per cent suggest that both humans and chimpanzees belong to the Homo genus [1]? (ii) Did Neanderthals represent “a distinct and separate species… which was displaced by the more recent arrival of Homo sapiens from Africa” [2]. (iii) Can “Neanderthal genes explain their failure to compete culturally” [6] and clarify “the origin of modern humans [5]. And, most importantly, (iv) can fat explain how the pre-human and human brain evolved?

Indeed, abundant research material from many sources synthesized by Horrobin [7], [8], [9] not only makes it reasonable to assume that genetic differences between Neanderthals and contemporary kinds of people were both important and limited in number but also suggests how this could explain the cultural inferiority of the former. Interestingly, the rationale which is summarized below also suggests how empirical studies into fat-related genes and biochemistry may clarify significant differences between humans and chimpanzees and can further our principal understanding of the evolution of the brain.