1 April 2005

Lecture 32

Reading, Chapter 7, Chapter 28

VI. Genes

F. Patterns of inheritance

5. Color blindness and X -linked inheritance.

There are traits governed by single genes that are on the sex chromosomes, X and y. Inheritance of these traits is different between males and females. They exhibit what is known as "sex-linked" inheritance.

Human males have one X chromosome that was inherited from their mother and one y chromosome that was inherited from their father. At meiosis in males, X and y pair as homologues and are separated into different gametes (thus, the sex of a child is determined by whether an X-bearing sperm or a y-bearing sperm fertilizes the egg cell). Despite their ability to pair as homologues, X and y do not have the same genes, for the most part. Thus, genes on the y chromosome will be inherited exclusively from the father while genes on the X chromosome will be inherited exclusively from the mother in male children. Also, recessive alleles on X or y will always be expressed in males, since no other alleles for the gene are present.

Human females have two homologous X chromosomes and no y chromosome. One X was inherited from the father and one from the mother. In females, genes on X are inherited similarly to genes on the rest of the chromosomes (known as autosomes). It is in males that inheritance of genes on the sex chromosomes (X and y) is different.

Red-green color blindness is the decreased ability to perceive some colors, especially red and green. It results from several possible mutations to genes on the X chromosome. This trait is recessive and therefore much more common in males than females, since females have two X chromosomes and must be homozygous for the mutated allele to be color blind. If males have the mutant allele on their single X chromosome, inherited from the mother, they will be red-green color blind.

G. Meiosis in humans

Meiosis generates haploid gametes for sexual reproduction. A number of mechanisms act before, during, and after meiosis to increase the genetic diversity between the resulting offspring, their parents, and their siblings. The risks and extra effort of sexual reproduction are considerable and yet nearly all organisms engage in some sort of sex. We are left with the hypothesis that the value of genetic diversity created by sex outweighs its costs with respect to the survival of a species over evolutionary time. Biologically, strength comes from diversity.

We will now consider meiosis and the events after in a human context. The first point to consider is the specialization of male and female human gametes and its impact on human reproduction.

1. Gamete formation in human males

Gamete formation in males results from meiosis and development of sperm cells in the walls of the semeniferous tubules in the testes. Meiosis generates four haploid sperm cells from a diplod cell called a primary spermatocyte. Half of the four sperm cells will have a y sex chromosome while the other half will have an X sex chromosome. These will give rise to male and female offspring, respectively, should they fuse with an egg cell.

After development, the sperm cells have a long tail containing microtubules that can slide across each other and cause a swimming movement, mitochondria at the base of the tail to provide ATP for the movement, a "head" with the haploid nucleus and also a large store of digestive enzymes that will digest a path for the nucleus through the layers of cells surrounding the egg.

Sperm cells are produced more or less continuously throughout the life of a male, beginning at puberty. On average, adult males produce 30 million new sperm cells each day. Recent studies indicate that their is some decline in the fertility of sperm after age 35 but, in general terms, males are capable of reproduction at any time from puberty until death. They experience little or no cycling of their reproductive potential on a monthly or annual basis.

a. Hormones

Regulation of sperm production is by chemical signals (hormones) produced in the brain. GnRH (gonadotropin releasing hormone) is produced in the hypothalamus of the brain and triggers release of Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) from the anterior pituitary gland into the blood. In males, LH and FSH present in the blood stimulate the secretion of testerone by cells called Leydig cells in the testes. Testosterone stimulates meiosis of cells in the semeniferous tubules that develop into sperm cells. Testosterone also circulates with the blood from the testes to other cells and tissues, leading to characteristics such as facial hair, muscle growth, and aggressive behavior.

A hormonal feedback system acts to maintain relatively stable levels of testosterone and sperm production in males. If blood levels of testosterone are high, release of LH and FSH by the anterior pitutiary is inhibited and secretion of testosterone by the Leydig cells of the testes slows. If large numbers of sperm cells have accumulated in the semeniferous tubules, a hormone called inhibin is produced in the testes that also inhibits release of LH and FSH by the anterior pitutiary.

b. Male contraception

The only effective methods of male contraception are surgically cutting the vas deferens, the tubes that supply sperm cells from the testes to the penis, and use of a condom. There has been considerable interest in development of a drug that reliably and reversibly prevents sperm production without serious side effects but this has been difficult to achieve. Drugs that prevent production of LH, FSH, or testosterone cause a loss of male characteristics that is usually undesirable. Drugs that inhibit cell division in the testes without also inhibiting cell division elsewhere, leading to side effects, are also difficult to find. A similar challenge is faced in finding chemotherapies for cancer, which attempt to block cell division in tumors without blocking it elsewhere or to specifically kill one cell type without killing others. Development of male contraceptive drugs is in progress but, at present, none are available.

c. Recent decreases in male fertility

Since 1960, there has been a remarkable decrease in human male fertility. Sperm counts (cells/ejaculate volume) have decreased roughly 40% and ejaculate volumes have decreased roughly 20% over the last 40 years. One hypothesis is that chemicals in soybeans that are similar to the female hormone estrogen, so-called "phytoestrogens", are a cause. Soybean oil and protein are widespread in food processing and production. Several recent studies show that consumption of soy products has no effect on male fertility, however. Agricultural chemicals have also been implicated. A recent field and lab study showed that trace amounts of the widely used herbicide atrazine seriously inhibit the development of male reproductive organs in frogs, perhaps contributing to worldwide declines in amphibian populations.

Despite reduced male fertility, there is no immediate concern about impaired human reproduction. The average ejaculate contains over 300 million sperm cells, only a few of which are required for fertilization.