Not too long ago, sleep deprivation made me commit a stupid mistake on the relations between evolution and development. I was corrected by a reader (nyuanshin), and now I justify myself by posting a link to an incredible article that proposes that cell condensations are morphogenetic units that mediate the interactions between genotype and phenotype. The abstract of the article follows:

Embryonic development and ontogeny occupy what is often depicted as the black box between genes – the genotype – and the features (structures, functions, behaviors) of organisms – the phenotype; the phenotype is not merely a one-to-one readout of the genotype¹. The gene's home, context, and locus of operation is the cell. Initially, in ontogeny, that cell is the single-celled zygote. As development ensues, multicellular assemblages of like cells (modules) progressively organized as germ layers, embryonic fields, anlage, condensations, or blastemata, enable genes to play their roles in development and evolution. As modules, condensations are fundamental developmental and selectable units of morphology (morphogenetic units) that mediate interactions between genotype and phenotype via evolutionary developmental mechanisms. In a hierarchy of emergent processes, gene networks and gene cascades (genetic modules) link the genotype with morphogenetic units such as condensations, while epigenetic processes such as embryonic inductions, tissue interactions and functional integration, link morphogenetic units to the phenotype. To support these conclusions I distinguish units of heredity from units of transmission and discuss epigenetic inheritance by tracing the history of relationship between embryology and evolution, especially the role(s) assigned to cells or to cellular components in generating theories of morphological change in evolution. The concept of cells as modular morphogenetic units is modeled and illustrated using the mammalian dentary bone.

I present here also figure 8 from Hall's paper, which you should go read NOW!

 

I would like to begin this post by stating that the title above should not be mistaken for a scala naturae-like view of brain evolution. I do not pretend, here, to imply any morphoclinic continuity in the brain of platyhelmintes, insects, fishes and mammsl. Instead, I will review a few articles on patterns of gene expression using these species as examples, emphasizing similarities but also pointing to differences.

The evolutionary psychology (herein refered to as “EP”) research programme was proposed by many psychologists – in special Leda Cosmides and John Tooby [cf. ref. 1] – as an “adaptationist” programme to study the evolution of psychological traits. This research programme spurred a lot of attention among scientists and non-scientists alike, and the attention it received from the media ended up creating an enormous unrest in the scientific community. On the one hand, psychologists tried to demonstrate that evolutionary psychologists were using evolutionary theory to attempt to eliminate competing theories within psychology without regard to evolutionary biology. According to them, the experiments led by evolutionary psychologists support a non-evolutionary psychological theory as strongly as an evolutionary one. On the other hand, evolutionary biologists shun the “adaptationist programme” as something that “regards natural selection as so powerful and the constraints upon it so few that direct production of adaptation through its operation becomes the primary cause of nearly all organic form, function and behaviour” [2]. In the middle, developmental biologists complain that EP has an almost preformationist vision of the mind [3,4], ignoring the epigenetic mechanisms that are, in fact, the selectable units of morphology that mediate the interactions between genotype and phenotype via evolutionary developmental mechanisms [5]. On this post, I will floss the dead horse and classify the body of critique to EP in 4 groups: evolutionary biology issues, neuroscience issues, developmental issues, and general epistemological issues.

 

Todd M. Preuss, Mario Cáceres, Michael C. Oldham, Daniel H. Geschwind (2004). Human brain evolution: insights from microarrays Nature Reviews Genetics, 5 (11), 850-860 DOI: 10.1038/nrg1469


In a recent post, I commented on article by Todd Preuss' research group, and compromised myself to a further attempt to describe his research programme here. As I said then, nyuanshin pointed me to Preuss' homepage, and I downloaded a few articles – including one review paper that appeared in Nature Reviews Genetics on the insights that were obtained from microarray studies to theories of brain evolution [1]. Of course, no article can be published in Nature Reviews Something if it does not involve speculations on something that is relevant to human beings, and thus this particular paper is called Human brain evolution: Insights from microarrays. Even though I do not support such “anthropocentric” attitude from high-impact journals, it is indeed a very good review, and I shall sum it up and digest it for the few of you who read this.

Exciting as these results could be, they are not without contradiction. Yu et al. [7] criticized the ASPM analysis on the basis that, even though computer simulations indicate that ASPM showed an unusual pattern of variation within the last 500 to 14,100 years, an empirical comparison of ASPM with other loci does not ensue evidence for positive selection on the abnormal spindle-like microcephaly associated (ASPM) gene in European populations in the past 6000 years, as postulated by Mekel-Bobrov et al. [4]. In the same direction, Currat et al. [8] suggested that the demographic histories examined by Lahn's crew [4] were only a small subset of all possible demographic histories; as such, other computational models of such demographic histories could (and indeed, do) generate the observed patterns of variation without appeal to the inferred positive selection. The obvious problem here is that Mekel-Bobrov et al.'s [4] and Evans et al.' [5] studie used computational models to estimate variation without considering alternative models or other empirical data. The evidence for the “ongoing adaptive evolution” of ASPM and microcephalin, thus, is not enough to reject the “null-hypothesis” that the observed variation can be explained by other, non-selectional variables.

This does not mean that those genes did not present evolutionary change in the human clade, though. Evans et al. [2] and Zhang [3] postulated that those genes were positively selected in the human lineage, even if there is no evidence of ongoing selection. As such, those oligonucleotide array studies demonstrated that ASPM and microcephalin underwent either large sequence changes or acceleration in the rate of nucleotide changes when Homo sapiens appeared. As Preuss et al. [1] review, however, evolutionary change occurred in other genes, as well. In the previous post on Preuss' group's work, I commented that there seems to be an increase in the expression of the THBS4 and THBS2 genes in cortex and caudate nucleus of humans when compared to chimpanzees and macaques. Another example is the FOXp2 gene – related to a human speech and language disorder [9] –, which encodes a protein that contains two human-specific amino-acids in positions that are conserved in other species [10]. FOXp1 and FOXp2 are also expressed in the brain of songbirds [11], and, as I recently learned in a FeSBE symposium held by Constance Scharff, knocking off FOXp2 in specific songbird pallial areas (HVC and area L) seriously impair the animals' capacity to learn new songs. In fact, as Butler and Hodos [12] put it, “[t]he avian vocalization pathways have evolved independently of those in mammals, with many similarities and some differences”. It seems, however that, among primates, a unique pattern of protein structure of the products from FOXp2 is found among humans. Preuss [13] argued that there is no evidence that new cortical areas evolved in the human lineage for language processing; “indeed, a reasonable case can be made that classical language areas have homologs in nonhuman primates”.

Down-regulation of gene expression is also seen in humans, in relation to other primates. The most striking change in this sense (pun unintended) is the loss of “a substantial fraction” of genes that encode olfactory receptor proteins [14]. It is probable that an enlarged olfactory system is linked to the feeding habits of carnivores [15,16], and, as such, should be diminished in herbivores and omnivores, including here Homo sapiens. It is interesting to notice that, even though prior theorists doubted the existence of a vomeronasal (accessory) olfactory system in some mammals – including human beings –, it has been demonstrated that this trait is probably retained in all mammals [17].

Cáceres et al. [18], using gene ontology classification [19], demonstrated that the genes that were in excess in human brains were those that were included in the categories of cell growth and/or maintenance and metabolism. Uddin et al. [20] did a similar gene-ontology analysis, and identified expression changes in transcription, translation and mRNA-processing genes. One should be directed to Preuss et al.'s [1] table 2 to take the full impact of those gene-ontology analyses.

What are the functional consequences of such elevated expression levels? Let the authors speak:

The elevated expression levels of many genes in the human brain, and their relationship to energy metabolism, indicates that the general level of physiological activity in the adult cerebral cortex might be higher in humans than in chimpanzees [[18, 20]]. Additionally, the upregulation in gene expression could be the result of an accumulation of mRNA molecules in human cells to allow for rapid responses to external stimuli. The human brain might also have adapted to the damaging effects of maintaining high rates of neural activity over the course of a long lifetime by increasing the expression of chaperones and other genes with neuroprotective functions [[18]].

The issue of what differences exist between human and nonhuman primate brains is a long-standing one. Human brains have been structurally reorganized during evolution, producing proportionately larger cortices, more direct projections from neocortex to the medulla, and enlarged lateral prefrontal cortices [21], as well as a meshwork pattern in the V1 visual cortex [22]. According to Striedter [21], those changes can be traced back to changes in brain size. It is only recently that the genes that are responsible for those evolutionary changes were identified, and their evolutionary history told, mainly due to those microarray studies. An exciting possibility – that of reconciling morphological and cladistic studies with molecular studies – begins to unfold in evolutionary neuroscience, thanks to those studies. Preuss' effort to review those microarray studies is helping to shape the future of evolutionary developmental neuroscience.

That's it for now. Go away, now. Go do something useful.

 

References:

 

[1] Preuss TM, Cáceres M, Oldham MC, Geschwind DH (2004). Human brain evolution: Insights from microarrays. Nature Reviews Genetics 5:850-860. http://dx.doi.org/10.1038/nrg1469

 

[2] Evans PD, Anderson JR, Vallender EJ, Choi SS, Lahn BT (2004). Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size. Human Molecular Genetics 13: 1139-1145.

 

[3] Zhang J (2003). Evolution of the human ASPM gene, a major determinant of brain size. Genetics 165: 2063-2070.

 

[4] Mekel-Bobrov N, Gilbert SL, Evans PD, Vallender EJ, Anderson JR, Hudson RR, Tishkoff SA, Lahn BT (2005). Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science 309: 1720-1722. http://dx.doi.org/10.1126/science.1116815

 

[5] Evans PD, Gilbert SL, Mekel-Bobrov N, Vallender EJ, Anderson JR, Vaez-Azizi LM, Tishkoff SA, Hudson RR, Lahn BT (2005). Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309: 1717-1720. http://dx.doi.org/10.1126/science.1113722

 

[6] Evans PD, Mekel-Bobrov N, Vallender EJ, Hudson RR, Lahn BT. Evidence that the adaptive allele of the brain size gene microencephaling introgressed into Homo sapiens from an archaic Homo lineage. PNAS Early Edition. http://dx.doi.org/10.1073/pnas.0606966103

 

[7] Yu F, Hill RS, Schaffner SF, Sabeti PC, Wang ET, Mignault AA, Ferland RJ, Moyzis RK, Walsh CA, Reich D (2007). Comment on “Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens”. Science 316: 370b. http://dx.doi.org/10.1126/science.1137568

 

[8] Currat M, Excoffier L, Maddison W, Otto SP, Ray N, Whitlock MC, Yeaman S (2006). Comment of “Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens” and “Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans”. Science 313: 172a. http://dx.doi.org/10.1126/science.1122712

 

[9] Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco APA (2001). A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413: 519-523.

 

[10] Enard W et al (2002). Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418: 869-872.

 

[11] Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA. Parallel FoxP1 and FoxP2 expression in songbirds and human brain predicts functional interaction. Journal of Neuroscience 24: 3152-3163.

 

[12] Butler AB, Hodos W (2005). Comparative Vertebrate Neuroanatomy. Second edition. Hoboken: John Wiley & Sons.

 

[13] Preuss TM (2000). What's human about the human brain? In: MS Gazzaniga (Ed.), The New Cognitive Neurosciences, Second Edition, pp. 1219-1234. Cambridge: MIT Press.

 

[14] Gilad Y, Man O, Paabo S, Lancet D (2003). Human specific loss of olfactory receptor genes. PNAS 100: 3324-3327.

 

[15] Gittleman JL (1986). Carnivore brain size, behavioral ecology, and phylogeny. Journal of Mammalogy 67: 540-554.

 

[16] Gittleman JL (1991). Carnivore olfactory bulb size: Allometry, phylogeny, and ecology. Journal of Zoology 225: 253-272.

 

[17] Eisthen HL (1997). Evolution of vertebrate olfactory systems. Brain, Behavior and Evolution 50: 222-233.

 

[18] Cáceres M, Lachuer J, Zapala MA, Redmond JC, Kudo L, Geschwind DH, Lockhart DJ, Preuss TM, Barlow C (2003). Elevated gene expression levels distinguish human fro non-human primate brains. PNAS 100: 13030-13035. http://dx.doi.org/10.1073.pnas.2135499100

 

[19] Ashburner M et al. (2000). Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nature Genetics 25: 25-29.

 

[20] Uddin M et al. (2004). Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain-gene expression profiles. PNAS 101: 2957-2962.

 

[21] Striedter GF (2005). Principles of Brain Evolution. Sunderland: Sinauer Press.

 

[22] Preuss TM, Coleman GQ (2002). Human-specific organization of primary visual cortex: Alternating compartments of dense Cat-301 and calbindin immunoreactivity in layer 4A. Cerebral Cortex 12: 671-691.