Sex differences in number of X chromosomes and X-chromosome inactivation in females promote greater variability in hearing among males

Abstract

Background: For more than 150 years, research studies have documented greater variability across males than across females ("greater male variability"-GMV) over a broad range of behavioral and morphological measures. In placental mammals, an ancient difference between males and females that may make an important contribution to GMV is the different pattern of activation of X chromosomes across cells in females (mosaic inactivation of one the two X chromosomes across cells) vs males (consistent activation of a single X chromosome in all cells). In the current study, variability in hearing thresholds was examined for human listeners with thresholds within the normal range. Initial analyses compared variability in thresholds across males vs. across females. If greater across-male than across-female variability was present, and if these differences in variability related to the different patterns X-chromosome activation in males vs. females, it was expected that correlations between related measures within a given subject (e.g., hearing thresholds at given frequency in the two ears) would be greater in males than females.

Methods: Hearing thresholds at audiometric test frequencies (500-6000 or 500-8000 Hz) were extracted from two datasets representing more than 8500 listeners with normal hearing (4590 males, 4376 females). Separate data analyses were carried out on each dataset to compare: (1) relative variability in hearing thresholds across males vs. across females at each test frequency; (2) correlations between both across-ear and within-ear hearing thresholds within males vs. within females, and (3) mean thresholds for females vs. males at each frequency.

Results: A consistent pattern of GMV in hearing thresholds was seen across frequencies in both datasets. In addition, both across-ear and within-ear correlations between thresholds were consistently greater in males than females. Previous studies have frequently reported lower mean thresholds for females than males for listeners with normal hearing. One of the datasets replicated this result, showing a clear and consistent pattern of lower mean thresholds for females. The second data set did not show clear evidence of this female advantage.

Conclusions: Hearing thresholds showed clear evidence of greater variability across males than across females and higher correlations across related threshold measures within males than within females. The results support a link between the observed GMV and the mosaic pattern of X-activation for females that is not present in males.

Keywords: Greater male variability; Hearing; Sex differences; X-chromosome inactivation.

Fig. 1

Schematic representation of X-chromosome activation in males vs. females. In placental mammals, females show a mosaic pattern of activation with one of the two X chromosomes activated in each cell. Males show consistent activation of the single (maternally contributed) X chromosome across all cells

Fig. 2

Combined influence of two X chromosomes can reduce phenotypic variability in females relative to males. For X-linked traits, the combined influence of two X chromosomes in females vs. the influence of a single X chromosome in males can produce GMV in trait quantity or quality (see text)

Fig. 3

Variance ratios (male variance/female variance) for hearing thresholds at all test frequencies. Values are greater than 1.0 (dashed line) at frequencies showing GMV. Stars indicate significant differences from 1.0 (*p < 0.05; **p < 0.01; ***p < 0.001)

Fig. 4

Correlations between hearing thresholds for males and females. Bars represent Pearson’s R correlations across ears at single test frequencies (left hand bars), between adjacent test frequencies in the left ear (middle bars) and between adjacent frequencies in the right ear (right-hand bars). Stars indicate significant differences in correlation for males vs. females (*p < 0.05; **p < 0.01, ***p < 0.001)

Fig. 5

Hearing thresholds at all test frequencies for males and females. Stars indicate significant differences between mean thresholds for males vs. females (*p < 0.05; **p < 0.01, ***p < 0.001)