Analysis of complex traits like obesity through the mismatch perspective requires defining the relevant environment of evolution (E1), the changed environmental context (E2) and the trait (T). Mismatch is a dysfunctional consequence of a trait (T) that evolved in one environment (E1) being placed in a changed environment (E2). However, defining the trait (T) is complicated if the dysfunctional trait is a novel outcome of E2 and is unlikely to have existed in E1.1

I suggest a solution in my dissertation.2 In the case of obesity, the ‘ancestral trait’ (T) is likely to be involved in energy homeostasis. In a mismatch model for obesity we must consider the ‘ancestral trait’ or its ‘functional’ form as T1. Obesity is T2, a dysfunctional mismatch arising due to T1 (functional energy homeostasis) acquiring harmful consequences in E2 (modern lifestyle). T1 is expected to behave adaptively in E1, however, when placed in E2 it leads to obesity.

Take the example of ambient temperature as a cause of obesity. Within ambient temperatures (thermoneutral zone or TNZ) the human body doesn’t spend much energy to maintain body temperature (homeothermy). If the temperature goes above or below the TNZ then the body increases energy expenditure at the cost of decreased energy stores (body fat).

Time spent in the TNZ has gone up in the last few decades. The average internal temperature in homes in UK has gone up from 15.8 Celsius in 1978 to 21.1 Celsius in 2007.3 A study involving 9 women showed higher heat-production at 22 Celsius vs 28 Celsius.4

An evolutionary perspective suggests that in some populations the genes underlying the trait of homeothermy acquire harmful consequences in a novel environment of constant ambient temperatures. Ancestral humans no doubt used clothing and shelter, however, air conditioning and central heating are environmental changes that have no evolutionary precedence.

In this example, the ‘ancestral trait’ (T1) is associated with homeothermy and eventually to energy homeostasis. It evolved in variable temperatures associated with ancestral human environments (E1) and played a role in maintaining homeothermy by calibrating energy intake and storage. When this trait is placed in novel environments of constant ambient temperatures (E2) it leads to a dysfunctional outcome because the stored energy is never utilized for thermal homeostasis and over time this could lead to excess fat storage and obesity (T2).

What do to about the mismatch?

To begin with, it must be remembered that this is a hypothesis. A scientist must test the hypothesis before calling for clinical and policy-related changes.

How does one test evolutionary hypotheses? Tinbergen’s framework suggests four questions to study a trait. (a) How does it work? (b) How does it develop? (c) What is it for? (d) How does it evolve? These questions explore the proximate (a & b) and ultimate causes (c & d). An analysis for T1 and T2 must explore these questions and if possible, simultaneously.5

Other clarifications are required as well. Models of ancestral environments are hard to construct and, as a result, such hypotheses are plagued with speculation. Where can we draw the evidence from? Sometimes, E1 can be constructed in contrast to E2. Are there aspects of E2 that were absent in E1? Central heating during winter seems to be a modern phenomenon. Is there evidence for changing environments (E1àE2) due to heating in modern homes? Yes, average room temperatures have indeed gone up in the last 40 years. Historical studies will offer an answer. Does increased average room temperature cause weight gain? There is tentative evidence for this; human energy expenditure goes up during mild cold exposure. More studies in a naturalistic context are needed to support this relationship. Is the trait functional in E1? Homeothermy is an evolved mammalian trait. A comparative study of homeothermy across related species to decipher the relevant selection pressures will provide clarifications. Is the trait dysfunctional in E2? The relevant physiological mechanism underlying homeothermy is brown adipose tissue (BAT). BAT expends energy through heat in response to the requirement of the body. Does time spent in TNZ affect the heat-producing capacity of BAT and does this lead to excess body fat? There is tentative evidence to support this, however, additional clinical studies will help in providing clarification.3

Only a multi-pronged research program that elaborates E1, E2, T1, T2 and their associated proximate and ultimate causes is expected to lead to clinically and societally relevant results.

Mismatch is not the only kind of dysfunction. Hypotheses of constraints, drift, and antagonistic pleiotropy must also be given appropriate consideration.


  1. Llyod L, Wilson DS, Sober E. Evolutionary mismatch and what to do about it: a basic tutorial ms. in final draft, to submit to Evolutionary Applications (waiting for other articles for issue). Evol Appl. 2011.
  2. Rao S. EvoS Lifestyle Project: A Randomized Controlled Trial to Test the Efficacy of a Paleolithic Diet. in progress
  3. Mavrogianni A, Johnson F, Ucci M, et al. Historic Variations in Winter Indoor Domestic Temperatures and Potential Implications for Body Weight Gain. Indoor + built Environ J Int Soc Built Environ. 2013;22(2):360-375.
  4. Dauncey MJ. Influence of mild cold on 24 h energy expenditure, resting metabolism and diet-induced thermogenesis. Br J Nutr. 1981;45(2):257.
  5. Tinbergen N. On aims and methods of Ethology. Z Tierpsychol. 1963;20(4):410-433.