Timing Is Everything

Timing Is Everything

by Patricia Babin

They say slow and steady wins the race, and that’s especially true of human developmental timing. Turns out that, in terms of development, humans are like the tortoise that started the race late and slow—yet still won!

Scientists have long suspected that delays in gene expression play a part in the obvious delays observed in human physical development compared to (other) animals. Developmental delay (known as “neotony”) in humans is not entirely surprising. We’ve all seen movies of the wobbly colt that finds its legs and walks within minutes of its birth. Yet human babies require about a year before they take their first steps.

Recently, scientists postulated that the delayed timing of gene expression in a newborn baby’s brain is, to some degree, responsible for humans’ increased intellectual ability.1 A team of 15 scientists from around the world set out to determine if humans experience postponement in early infancy in the gene expression required for brain development. They began by obtaining brain tissue from humans, chimpanzees, and rhesus macaques. The human samples ranged in age from 0 to 40 years; samples from other species were the equivalent ages.

In the first phase of the study, the researchers identified 7,598 genes expressed in the three species as indicated by the presence of the same mRNA. They then analyzed each gene’s expression pattern with regard to age, sex, and species. Their first astounding discovery was that in all three species, gene expression in the brain underwent enormous change during infancy. In humans, 71 percent of the genes underwent a change in expression level during the first few years of life, with 50 percent undergoing a change in expression level during the first year. Following infancy, the changes were much less dramatic. In this sense, all three species showed the same general pattern with regard to the gene expression in the brain. However, in humans 48 percent of the genes showing an age-dependent expression pattern were either expressed at a significantly different level or showed a significantly different pattern of expression compared to chimps.

In order to categorize the difference in the species’ genes expression timing, the researchers chose to use the rhesus macaques as the outgroup (a reference group). In other words, if at least one of the species has the same expression pattern for a particular gene as the macaques, that pattern will be deemed to be the “standard” pattern of expression for that gene. Doing this allowed the scientists to establish four categories of gene expression:

  1. Human neotony: human gene expression was delayed relative to chimp and macaque expression
  2. Human acceleration: human gene expression was accelerated relative to chimp and macaque expression
  3. Chimp neotony: chimp gene expression was delayed relative to human and macaque expression
  4. Chimp acceleration: chimp gene expression was accelerated relative to human and macaque expression

Of the 7,598 genes, 299 could be assigned unambiguously to one of these categories. In round numbers, human neotony occurred twice as much as the other categories. 

What is the significance of all this data? Does it really make a difference when a gene is expressed? Actually, it does. For example, experiments have demonstrated that mice form an additional vertebra due to a one day delay (out of a 20-day gestation period) in expressing some of the genes involved in vertebrae formation. The additional vertebra resulted in shifting the beginning of the sacrum region toward the mouse’s posterior.2

How does this relate to human uniqueness and intelligence? One theory suggests that the delay in expressing genes in the brain means that the brain remains in a “plastic” state for an extended time. In this state, additional synaptic connections can be formed, resulting in the acquisition of knowledge and memories. Additional time spent in the plastic state may explain some of the biological basis for humanity’s vast intellectual abilities. 

Another example of the “timing is everything” principle can be observed in the mid phase of human embryogenesis (17 to 23 weeks)—a critical period for the process of brain development. Though electrical activity can be detected in the brain as early as the fifth or sixth week after conception, synaptic connections begin to form in earnest at the beginning of the mid phase. By the end of this phase, the baby’s brain is stable, thus, marking the beginning of the time at which a premature baby has a chance of surviving outside the womb. In a recent paper, scientists reported that 76 percent of human genes are expressed in the developing brain during the mid phase.3 This is the most radical known example of a complex organism expressing this much of its genome4 in one organ (the brain) at one time. It does not occur in other human tissues and it is not believed to occur in any other organism.

Clearly, gene expression timing in fetal and infant brains plays an important role in the development of human intellect. However, scientists are identifying yet many more factors essential in developing that intellect. In future Today’s New Reasons to Believe, I will discuss some of these other factors.

  1. Mehmet Somel et al., “Transcriptional Neotony in the Human Brain,” Proceedings of the National Academy of Sciences, USA 106 (April 7, 2009): 5743–748.
  2. Jozsef Zákány, Matthieu Gérard, Bertrand Favier, and Denis Duboule, “Deletion of a HoxD Enhancer Induces Transcriptional Heterochrony Leading to Transposition of the Sacrum,” The EMBO Journal 16 (July 16, 1997): 4393–402.
  3. Matthew B. Johnson et al., “Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis,” Neuron 62 (May 28, 2009): 494–509.
  4. Note: The authors of this study consider the complete human genome to consist of 17,421 genes. This quantity represents the complete set of well-annotated human genes.