Human Evolution Renewed: A Search for Ecologial and Genetic Reasons Behind Our Humanity

The study of human evolution is a topic of great interest on many levels. Since the publication of Charles Darwin’s On the Origin of Species in 1859, its significance has permeated our everyday lives, leading to debates of creationism versus evolution on general, social, and cultural levels. More recently, the completion of the Human Genome Project in 2003 has made possible comparisons of DNA sequences between humans and closely related organisms. At Yale, evolutionary biologists are approach­ing the subject both from a macroscopic, ecological standpoint and from a micro­scopic, genetic view.

How Do We Define Evolution?

Stephen Stearns, Professor of Ecology and Evolutionary Biology, is currently seek­ing evidence for the existence of modern day natural selection among the human population. Many people doubt that natu­ral selection is still at work in the popula­tions of developed countries because of the security and overall well-being that pervades society. With the advent of mod­ernized medicine, many of the injuries, diseases, and viruses that plagued humans in the past have been effectively eliminated.

Stearns has studied the evolution of humans and other organisms, utilizing the theory of life history evolution. Life history evolution directly relates to natural selec­tion by seeking to investigate its effects on phenotypes, rather than genotypes, within a given organism’s population. In biology, phenotypes are the observable traits or characteristics of organisms while geno­types are the genetic traits that cannot be readily observed.

Specifically, Stearns observes the life history traits of organisms to evaluate the progress of evolution that has occurred in their populations. These traits include: size at birth, growth pattern, age and size at maturity, number, size, and sex ratio of offspring, age-and size-specific reproduc­tive investments, age- and size-specific mor­tality schedules, and lifespan. All of these traits relate back to reproductive success and its role in natural selection. This is the underlying principle for a statistical analysis being performed by Stearns, along with Dr. Sean Byars, his postdoctoral fellow, and Dr. Douglas Ewbank, Professor of Sociology at the University of Pennsylvania.

Pass the Statins: Using Cholesterol to Study Evolution

The data they are using was collected in the Framingham Heart Study. Started in 1948, the study is an ongoing project that seeks to determine the major causes of cardiovascular disease (CVD). The medical histories of more than 14,400 patients over three generations from Framingham, MA have been compiled and studied. So far, the Framingham Study has been responsible for pointing out major causes of CVD including high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity.

While this population study provides a substantial dataset for Stearns to utilize, the structure of the data is designed solely for medical purposes, without consideration toward scientific research. Thus, Stearns has focused only on analyzing blood cho­lesterol data.

The major defining elements of natural selection are varying degrees of reproduc­tive success. Therefore, Stearns sought to identify any statistical correlation between levels of blood cholesterol in women and their reproductive success, or in this case, the number of children they gave birth to during their fertile phases.

First, the population set given in the Framingham Study was reduced by omit­ting all the male patients and taking out the women who have not yet reached menopause or who were already approach­ing menopause when they first entered the study. After these eliminations, 4,123 women remained. From these subjects, 21,533 measures of total cholesterol data were extracted and rendered into a 3 dimen­sional surface of best fit using a generalized additive model.

The two predictors, or independent variables, were the ages and years in which total cholesterol was measured; the response, or dependent, variable was the total cholesterol.

In Figure 1, the different colored dots belong only to a subset of data points shown for clarity and reference. Each color belongs to an individual female patient.

The red and orange points represent the total cholesterol levels for two women’s cholesterol measures that were studied in the Original Cohort, or the first genera­tion in the study. The two shades of green represent two women from the Offspring Cohort (the second generation of the study). Finally, the blue dots constitute data for two women from the Third Cohort (third generation).

As seen on the graph, there is a rough trend that indicates a general decrease of total cholesterol levels in women from the 1950s to the present.

Figure 1. Generalized additive model surface of best fit for total cholesterol by Age and Year measured for a subset of women in the Framingham Heart Study Population. (Image courtesy of Stephen Stearns)

Overall, this data helps simplify the large dataset of numbers given in the Framing­ham Heart Study before attempting to correlate them with the women’s childbirth history. The gray surface of best fit was cre­ated based on analysis of the residual values for all the total cholesterol measures, which then acts as an easier means of representing the all the data on total cholesterol from women measured across different ages over different years.

After seeing how the total cholesterol in these women varied with age and year of measure, the residual values obtained from Figure 1 were then combined in an analysis with lifetime reproductive success of the women (the number of children she produced over her lifetime). In most evolutionary studies, biologists use a selection gradient in which they test the association of a certain phenotypic trait by the fitness or reproductive success in a given population.

In Figure 2, the blue line is the selec­tion gradient calculated as a Poisson link, which is used to test for any indication of directional selection for total cholesterol in which cholesterol level exhibits a linear relationship with reproductive success. On the other hand, the red line is calculated as a quadratic model to test for stabiliz­ing selection for total cholesterol, where women with mean cholesterol would have the greatest reproductive success.

“From this graph it appears that women who have slightly lower cholesterol may have had higher fitness in terms of lifetime reproductive success,” said Byars.

Still, the research of Stearns and his col­leagues remains in the preliminary stages. More statistical analysis is needed to affirm current findings and seek out additional correlations between reproductive success and medical history traits.

Further studies have suggested that longevity in women is slightly decreased with greater reproductive activity, but this finding has yet to be finalized.

Figure 2. Generalized linear model to test for directional and stabilizing selection in total cholesterol. (Image courtesy of Stephen Stearns)

Moving Down to DNA

One well-known trait that helps distin­guish humans from their primate ancestors is the opposable, or prehensile, thumb. This allows humans to rotate their thumbs toward their palms and turn back against the other four fingers, providing greater grip, more accurate motor skills, and overall higher dexterity of the hand.

Other less known morphological distinc­tions exist between primates and humans; these include increased thumb length rela­tive to the other fingers or digits and more inflexible, shortened toes, which aid in bipedalism, or the ability to walk upright on two feet.

All of these morphological differences arise during the embryonic stage of human development, during which limb develop­ment is altered as a result of differences in gene expression between humans and other primates.

These differences are attributed to changes in the human genome, occurring over the 6 million years since humans branched from chimpanzees, that now alter gene regulation related to limb devel­opment.

Expressing Genes

Gene expression is the process in which hereditary information from DNA is used as a template to create a protein. When most students learn about DNA and its role in gene expression, they are usually taught the general flow of genetic information: during transcription, DNA is used as a template to make RNA, a single-stranded nucleotide polymer constructed from a set of four nucleotides; then, during transla­tion, that RNA serves as the template to create a protein, a polymer made from a set of twenty amino acids.

The nucleotide sequences in RNA responsible for coding for proteins are called exons, while the sequences and regions of RNA that do not code for pro­teins are called introns. Introns are spliced out of an RNA molecule before translation occurs.

In the past, scientists considered the noncoding sequences of DNA to be “junk DNA,” as they had no identifiable purpose. However, regulatory roles, including the enhancement or inhibition of gene expres­sion, were discovered for some noncoding sequences.

Noncoding is Not Non-informative: Meaning in Conserved Sequences

The laboratory of James Noonan, Assis­tant Professor of Genetics, has discovered 992 noncoding DNA sequences in humans that have been conserved through evolu­tion. In other words, these sequences are similar or identical to sequences in related organisms such as primates, particularly chimpanzees and rhesus macaques. Some noncoding sequences, on the other hand, evolve much more rapidly, particularly for humans.

One such sequence is the human-accelerated conserved noncoding sequence 1 (HACNS1), which is the most rapidly evolving human noncoding sequence known. This sequence consists of 546 base pairs and has accumulated 16 human-specific nucleotide substitutions.

The goal of Noonan’s work was to explore the differences in limb develop­ment between humans and other primates that are associated with HACNS1.

The results of his research suggest that HACNS1 enhances gene expression in the anterior limb bud, pharyngeal arches, and developing ear and eye. Morever, this enhancer activity persisted across multiple developmental stages.

Figure 3. Expression patterns from the HACNS1 enhancer and analogous sequences from chimpanzee and rhesus monkeys. Arrows indicate limb bud positions where reproducible reporter gene expression is present or absent. A representative HACNS1 embryo is shown at top to illustrate the relevant anatomical structures. (Image courtesy of Stephen Stearns)

Future Work

The exact method by which HACNS1 obtains enhanced gene expression activity through its unique substitutions has yet to be determined. The role of the intron in which HACNS1 is located in limb develop­ment also remains unknown.

Learning the role of HACNS1 in human morphological evolution requires additional lines of evidence, including the analysis of expression of the introns during human development and the generation of HACNS1-targeted replacement mice.

Further research may shed light on the molecular causes of the differences between humans and our primate cousins.

About the Author
ERIC LI is a sophomore in Branford College planning to major in economics.

The author would like to thank Professor Stephen Stearns and Professor James Noonan for the information they provided on their valuable research.

Further Reading

  • Stearns , Stephen C. 1992. The Evolution of Life Histories. New York: Oxford University Press. p. 9-18.
  • Shyam P, and others. 2008. Human-specific gain of function in a develop­mental enhancer. Science 321: 1346-1350.